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- Detecção de hipóxia microrregional no Cortex Cerebral mouse por imagem de dois fótons de fluorescência endógena NADH
Other Publications (200)
- Revista Chilena De Infectología : órgano Oficial De La Sociedad Chilena De Infectología
- Frontiers in Genetics
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- Canadian Journal of Neuroscience Nursing
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- Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
- Antiviral Therapy
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- Arquivos De Neuro-psiquiatria
- Arquivos De Neuro-psiquiatria
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- The Ceylon Medical Journal
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Articles by Jharon N. Silva in JoVE
Detecção de hipóxia microrregional no Cortex Cerebral mouse por imagem de dois fótons de fluorescência endógena NADH
Oksana Polesskaya1, Anita Sun2, Gheorghe Salahura2, Jharon N. Silva1, Stephen Dewhurst1, Karl Kasischke3
1Department of Microbiology and Immunology, University of Rochester Medical Center, 2Center for Neural Development and Disease, University of Rochester Medical Center, 3Deptartment of Neurology, Center for Neural Development and Disease, University of Rochester Medical Center
Aqui nós descrevemos um método para visualizar diretamente hipóxia tecidual microrregional no córtex do rato
Other articles by Jharon N. Silva on PubMed
[In Vitro Antifungal Susceptibility, in Vivo Antifungal Activity and Security from a Natural Product Obtained from Sunrise Oil (AMO3) Against Dermatophytes]
Revista Chilena De Infectología : órgano Oficial De La Sociedad Chilena De Infectología. Dec, 2011 | Pubmed ID: 22286673
This work studied safety and antifungal activity of ozonized sunflower oil (AMO3) against dermatophytes. AMO3 was prepared through a new original process that modifies the oil before ozonation by alcoholic catalytic esterification. Susceptibility was studied in 41 dermatophytes by agar diffusion and broth microdilution tests. The experimental model to assess the topical safety of the oil included 60 CF1 mice divided in three groups that were treated with vaseline (control), 1% AMO3 and 50% AMO3 (overdose), respectively. Then, experimental dermatophytosis was induced in CF1 mice. Seventy-five individuals were selected and divided in 5 groups that were treated once a day with placebo, cream with 1%, 2% and 3% AMO3 plus an untreated control group. This new natural product showed antifungal activity against all strains studied. The MIC ranged between was 0,125 and 1%, while minimum fungicidal concentration (MFC) was 2%. The application of vaseline and AMO3 1% and 50% did not produce clinical or histopathological lesions. The mice with dermatophytosis that were treated with 1%, 2% and 3% AMO3 showed 100% clinical cure and 94% average mycological cure, exceeding placebo and control groups (p < 0,05). This product exhibits high antifungal activity and could be a safe alternative for ringworm topical treatment.
Frontiers in Genetics. 2011 | Pubmed ID: 22303406
Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.
Advances in Virology. 2011 | Pubmed ID: 22312333
Feline coronavirus (FCoV) is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP). Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.
Medicinal Chemistry (Shāriqah (United Arab Emirates)). Nov, 2011 | Pubmed ID: 22313301
A series of 32 L-serinyl hydrazone derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv, being also evaluated their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). The compounds 8c, 8e, 8h and 8i, were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity between 25 and 100μg/mL, which can be compared with that of the tuberculostatic drug D-cicloserine (5-20μg/mL).
The New Zealand Dental Journal. Dec, 2011 | Pubmed ID: 22338201
To report on the clinicopathological aspects of odontogenic keratocysts (OKC)/keratocystic odontogenic tumours (KCOT) presenting in a New Zealand population.
The New Zealand Dental Journal. Dec, 2011 | Pubmed ID: 22338202
To describe the demographic characteristics of patients undergoing orthognathic surgery at the University of Otago over a nine-year period.
Association Between Time-to-presentation and Clinical Outcome in Patients with Subarachnoid Hemorrhage: an Observational Study
Canadian Journal of Neuroscience Nursing. 2011 | Pubmed ID: 22338211
Headache is the most common presenting symptom of subarachnoid hemorrhage (SAH), ranging from mild headache to the "worst headache of my life". As headache is often non-specific, patients may not seek immediate medical attention, though prompt medical and surgical management is expected to improve clinical outcomes. In this study, we explore the independent association between duration from onset of symptoms to presentation at an emergency department (ED) and clinical outcomes after SAH.
Revista Médica De Chile. Oct, 2011 | Pubmed ID: 22286724
Background: Restrained eaters (RE) are a group of individuals who constantly restrict their eating. However, they usually alternate restriction with periods of overeating. Aim: To evaluate the possible association of CRF-BP and SLC6A4 gene polymorphisms with chronic alimentary restriction. Material and Methods: The Spanish version of the Revised Restraint Scale was applied to 132 women aged 18 to 25 years. They were divided in a group classified as restrained eaters (RE) and a group of unrestrained eaters. The 5-HTTLPR and CRF-BPs11 polymorphisms of the SLC6A4 and CRF-BP genes were evaluated by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. Results: There was a significant association between the s/s homozygous genotype for the 5-HTTLPR polymorphism of SLC6A4 gene and RE condition (p = 0.033). However, this association was not observed for the CRF-BPs11 polymorphism. Conclusions: The presence of s/s genotype is associated with the RE condition, being the presence of a s allele, a risk factor for this condition.
The Impact of Sleep-Disordered Breathing on Body Mass Index (BMI): The Sleep Heart Health Study (SHHS)
Southwest Journal of Pulmonary & Critical Care. Dec, 2011 | Pubmed ID: 22288025
INTRODUCTION: It is well known that obesity is a risk factor for sleep-disordered breathing (SDB). However, whether SDB predicts increase in BMI is not well defined. Data from the Sleep Heart Health Study (SHHS) were analyzed to determine whether SDB predicts longitudinal increase in BMI, adjusted for confounding factors. METHODS: A full-montage unattended home polysomnogram (PSG) and body anthropometric measurements were obtained approximately five years apart in 3001 participants. Apnea-hypopnea index (AHI) was categorized using clinical thresholds: < 5 (normal), ≥ 5 to <15 (mild sleep apnea), and ≥ 15 (moderate to severe sleep apnea). Linear regression was used to examine the association between the three AHI groups and increased BMI. The model included age, gender, race, baseline BMI, and change in AHI as covariates. RESULTS: Mean (SD) age was 62.2 years (10.14), 55.2% were female and 76.1% were Caucasian. Five-year increase in BMI was modest with a mean (SD) change of 0.53 (2.62) kg/m(2) (p=0.071). A multivariate regression model showed that subjects with a baseline AHI between 5-15 had a mean increase in BMI of 0.22 kg/m(2) (p=0.055) and those with baseline AHI ≥ 15 had a BMI increase of 0.51 kg/m(2) (p<0.001) compared to those with baseline AHI of <5. CONCLUSION: Our findings suggest that there is a positive association between severity of SDB and subsequent increased BMI over approximately 5 years. This observation may help explain why persons with SDB have difficulty losing weight.
A Multi-residue Method for the Determination of Pesticides in High Water Content Matrices by Gas Chromatography-single Quadrupole Mass Spectrometry with Electron Ionisation (EI-GC/MS)
Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. Dec, 2011 | Pubmed ID: 22292605
An EI-GC/MS method for the determination of pesticide residues in vegetable matrices with high water content was validated using papaya samples. The validation of a multi-residue pesticide method was in agreement with national and international regulations enabling the Ministry of the Agriculture, Livestock and Food Supply of Brazil to cover a large number of matrices and pesticide residues in its monitoring and control programmes. The extraction used 60 mL of ethyl acetate and 30 g of sample previously processed. After extraction, clean-up of all the extracts was carried out by percolation through GBC cartridges. The samples were then injected in an EI-GC/MS system. Calibration curves were prepared in quadruplet by fortifying blank extracts with a standard solution containing all the pesticides studied at 0.000, 0.005, 0.010, 0.020, 0.030, 0.050, 0.080 and 0.100 mg kg(-1). For the recovery study, blank samples were fortified at 0.010, 0.020, 0.030, 0.050 and 0.080 mg kg(-1) and then submitted to the extraction procedure. The complete procedure was repeated over four different days by two analysts. The regression parameters of calibration curves were calculated for each validation day. Linearity, selectivity, specificity, robustness, limits of detection and quantification were also assessed. The uncertainty was estimated for each analyte at each spike level studied. The method had recoveries between 91% and 105% and precision results ≤20%. Limits of quantification were below or equal to the maximum residue limits (MRLs) regulated by Brazilian legislation. The MRLs of the selected pesticides are not regulated by CODEX Alimentarius. The results are also in agreement with SANCO/10684/2009.
Recurrent and Persistent Cytomegalovirus Infection in a Kidney Recipient Caused by the L595S Mutation in UL97 Phosphotransferase Gene
Antiviral Therapy. Oct, 2011 | Pubmed ID: 22293247
Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug-resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a CMV-seropositive donor (D(+)/R(-)), and who developed clinical GCV resistance, confirmed by mutation in viral UL97 phosphotransferase responsible for GCV activation. Under prophylactic therapy with intravenous GCV for 6 weeks post-transplantation, he developed severe anaemia and hepatic enzyme increases, probably due to drug side effects. At this moment, the drug was discontinued and he started to be monitored by pp65 antigen test. At week 10 post-transplantation, he presented fever, myalgia, thrombocytopenia and neutropaenia, with a positive CMV antigen test. During treatment with intravenous GCV, antigenaemia assay demonstrated a higher number of positive cells, requiring GCV at higher doses. Pre-emptive therapy lasted for 31 days and he started the maintenance therapy with oral GCV. However, antigenaemia assay demonstrated an extremely high number of positive cells, and he was rehospitalized and prescribed intravenous GCV. Severe leukopaenia led to GCV interruption, but immunosuppressive dose reduction helped to control the active CMV infection. GCV-resistant CMV infection resulted in increased morbidity, rehospitalization episodes and increased costs; therefore, implementation of resistance diagnostic tests in the transplantation routine is of great importance. We documented the first case of GCV-resistant CMV infection due to the L595S mutation in UL97 phosphotransferase gene in a kidney recipient from Bahia state, Brazil.
Transcranial Sonography As a Diagnostic Tool for Parkinson's Disease: a Pilot Study in the City of Rio De Janeiro, Brazil
Arquivos De Neuro-psiquiatria. Dec, 2011 | Pubmed ID: 22297874
In Brazil there is no systematic study on Transcranial Sonography (TCS), a neuroimaging method that depicts echogenic deep brain structures using ultrasound.
Arquivos De Neuro-psiquiatria. Dec, 2011 | Pubmed ID: 22297886
Literature has shown that extent of tumor resection has an impact on quality of life and survival of patients with gliomas. Intraoperative MRI has been used to increase resection while preserving procedure's safety.
Arquivos De Neuro-psiquiatria. Dec, 2011 | Pubmed ID: 22297887
The authors advocate a modernization of the neurologic exam with regard to the evaluation of static equilibrium through the application of some easily performed and interpreted bedside maneuvers like the Clinical Test of Sensory Integration and Balance - modified and the Functional Reach Test. The authors also believe that these and other assessments, such as that of the risk of falling for elderly patients, should be incorporated into the routine neurological examination.
Arquivos De Neuro-psiquiatria. Dec, 2011 | Pubmed ID: 22297888
The authors propose that the neurological exam needs reevaluation with respect to the dynamic balance test (walking). Validated tests such as: preferred and maximum gait speed, dynamic gait index, five-times-sit-to-stand test, timed up & go cognitive and manual, should be part of the neurological examination routine. In the neurological exam of older patients, these same bedside tests bring the plus of evaluation the risk of occasional falling.
The Ceylon Medical Journal. Dec, 2011 | Pubmed ID: 22298207
To validate the Sinhala version of the Montreal Cognitive Assessment (MoCA) scale in screening for dementia.
The Ceylon Medical Journal. Dec, 2011 | Pubmed ID: 22298214
The Ceylon Medical Journal. Dec, 2011 | Pubmed ID: 22298222
The Malaysian Journal of Pathology. Dec, 2011 | Pubmed ID: 22299213
Retroperitoneal liposarcoma is a rare solid tumour of mesenchymal origin with an incidence of 2.5 per million population. We report what is, to the best of our knowledge, the first case in the English literature of retroperitoneal liposarcoma in an adult patient with Down syndrome. The tumour was surgically resected with no use of adjuvant chemotherapy or radiation. No recurrence was found at follow-up 2 months postoperatively. Clinicians should consider retroperitoneal liposarcoma in the differential diagnosis of abdominal distention in adult patients with Down syndrome.
Revista Gaúcha De Enfermagem / EENFUFRGS. Dec, 2011 | Pubmed ID: 22299273
This is a phenomenological study that aimed to understand the experience of the student enrolled in both the Bachelor and the teaching undergraduate degree in nursing at the same time. Interviews with eight nursing students from a public university of Minas Gerais, Brazil, were undertaken. Analyses were conducted based on the social phenomenology of Alfred Schütz. Results showed that according to the pupils, there is no connection between the teaching courses and the Bachelor ones, but they also highlighted that the teaching degree helps educational activities in nursing. The students have interest in working with health education and to become nursing teachers. They also consider that the dual degree allows the expansion of knowledge and generates better expectations related to professional practice. However, it has gaps which need to be reviewed by those who work in nursing education, addressing the specific theoretical and practical needs of nursing students.
Revista Gaúcha De Enfermagem / EENFUFRGS. Dec, 2011 | Pubmed ID: 22299276
This article aims to analyze the patents registered in the nursing area, since these patents may be used as an indicator of the technological development in the area. It presents and discusses national technological productions, tracked through the "nursing" keyword, patented in the period from 1990-2009. This is a retrospective documental research, using, as a source, data from the National Industrial Property Institute (INPI). The information gathered is discussed in relation to the appropriation of the technologies, the incentive to develop them and register them as a source of knowledge in the nursing field, aiming the practice of care. Light and light hard technology productions are increasing in the nursing field. However, these are not registered and patented. The technological advance in the nursing field is emergent and needs policies for its development.
Economic Injury Level for the Coffee Berry Borer (Coleoptera: Curculionidae: Scolytinae) Using Attractive Traps in Brazilian Coffee Fields
Journal of Economic Entomology. Dec, 2011 | Pubmed ID: 22299352
The currently existing sample procedures available for decision-making regarding the control of the coffee berry borer Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae) are time-consuming, expensive, and difficult to perform, compromising their adoption. In addition, the damage functions incorporated in such decision levels only consider the quantitative losses, while dismissing the qualitative losses. Traps containing ethanol, methanol, and benzaldehyde may allow cheap and easy decision-making. Our objective was to determine the economic injury level (EIL) for the adults of the coffee berry borer by using attractant-baited traps. We considered both qualitative and quantitative losses caused by the coffee borer in estimating the EILs. These EILs were determined for conventional and organic coffee under high and average plant yield. When the quantitative losses caused by H. hampei were considered alone, the EILs ranged from 7.9 to 23.7% of bored berries for high and average-yield conventional crops, respectively. For high and average-yield organic coffee the ELs varied from 24.4 to 47.6% of bored berries, respectively. When qualitative and quantitative losses caused by the pest were considered together, the EIL was 4.3% of bored berries for both conventional and organic coffee. The EILs for H. hampei associated to the coffee plants in the flowering, pinhead fruit, and ripening fruit stages were 426, 85, and 28 adults per attractive trap, respectively.
Toxins. Dec, 2011 | Pubmed ID: 22295174
PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three-dimensional structure, the natural diversity of PA1b and its structure-function relationships.
Descriptions of a New Brazilian Tacora Species and the Female of Tacora Saturata, and a Key to the Species of the Genus (Insecta, Hemiptera, Cicadellidae, Cicadellini)
ZooKeys. 2011 | Pubmed ID: 22303120
Tacora johanni, a new species from Rondônia State, North Brazil, is described and illustrated. The new species can be recognized by the male genital features, especially the subgenital plates with the basal half distinctly expanded and with outer lateral margin round, the long and slender preapical pygofer process, and the styles with apical half strongly curved. Also, the genus is recorded for the first time from Venezuela, based on specimens of Tacora saturata Young, 1977, while the female of this species (here described in detail for the first time) shows two unusual features of the genitalia. A key to males of all known Tacora species and a map showing the known distribution of the genus are provided.
Using Appreciative Inquiry to Facilitate Implementation of the Recovery Model in Mental Health Agencies
Health & Social Work. Nov, 2011 | Pubmed ID: 22308878
This article describes an organizational development tool called appreciative inquiry (AI) and its use in mental health to aid agencies implementing recovery model services. AI is a discursive tool with the power to shift dominant organizational cultures. Its philosophical underpinnings emphasize values consistent with recovery: community, empowerment, and positive focus. Recent research in the field of mental health demonstrates the salience of organizational cultural context in affecting new service adoption. This article explores how AI could be helpful in shifting an organization's culture to render it compatible with recovery through descriptions of two mental health centers' use of the tool. The experiences described indicate that AI, if used consistently, empowers staff. The article concludes with consideration of the implications of this empowerment for recovery model implementation and directions for future research.
Archivos Latinoamericanos De Nutrición. Jun, 2011 | Pubmed ID: 22308939
In this study the chemical composition and iron bioavailability of hull and hull-less soybean flour from the new cultivar UFVTN 105AP was evaluated. The hemoglobin depletion-repletion method was used in Wistar rats. Soybean hull flour presented 37% more total dietary fiber and higher content of iron than hull-less soybean flour. The phytate:iron molar ratio, however, was 2-fold lower in the soybean hull flour in compared to the hull-less soybean flour. Animals fed soybean hull flour presented hemoglobin gains similar to those of the control diet group (p > 0.05). The Relative Biological Values of hull and hull-less soybean flour were 68.5% and 67.1%, respectively, compared to the control group. Heat-treated soybean hull flour (150 degrees C/30 minutes) showed high content of iron and low phytate, which favors the iron bioavailability. Thus, the soybean hull flour is a better source of dietary fiber and iron than hull-less soybean flour at comparable bioavailabilities.
[Development of Mixed Beverages Made of Caja (Spondias Mombin L.) and Cashew Apple (Anacardium Occidentale) Added of Fructooligosaccharides and Inulin]
Archivos Latinoamericanos De Nutrición. Jun, 2011 | Pubmed ID: 22308948
The purpose of this work was to develop three mixed drinks based on caja (Spondias mombin L.) and cashew apple (Anacardium occidentale) pulps, added prebiotic ingredients and to evaluate their chemical, physicochemical and sensory properties. Four formulations with combinations of two pulp fruit, sucrose and prebiotic ingredients (Standard inulin, inulin high performance-HP-and fructooligosaccharides FOS) were developed. The mixed drinks were submitted the following analysis pH, acidity, soluble solids, sugars, ascorbic acid, total carotenoids, total polyphenols and acceptance ratings of the sensory attributes such as: consistency, sweetness and overall impression, attitude and consumers purchase preference. The pH, total soluble solids and polyphenol results showed difference (p < or = 0.01) significant, while for the analysis of total acidity, sugars, ascorbic acid and carotenoids, it was not observed significant difference. The sensory attributes evaluates showed results ranging in scale between "I did not like or disliked "and" liked "(average 5.80 to 7.06). The attributes sweetness, consistency and attitude of buying showed no difference (p > 0.05) between drinks, however, differed significantly (p < or = 0.05) for the attribute of overall impression. The drink with FOS showed a similar acceptance when compared to traditional (sucrose) drink, showing an option of meeting the functional food expectations of consumers, who seek healthy, nutritious and tasty foods.
A Multicenter Feasibility Study of Chronic Graft-versus-host Disease According to the National Institute of Health Criteria: Efforts to Establish a Brazil-Seattle Consortium As a Platform for Future Collaboration in Clinical Trials
Revista Brasileira De Hematologia E Hemoterapia. 2011 | Pubmed ID: 22328863
BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75%. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.
Optimization of Production of Extracellular Polymeric Substances by Arthrobacter Viscosus and Their Interaction with a 13X Zeolite for the Biosorption of Cr(VI)
Environmental Technology. Oct, 2011 | Pubmed ID: 22329145
In this work we aimed to optimize the production of extracellular polymeric substances (EPS) by an Arthrobacter viscosus biofilm supported on 13X zeolite to be used in the biosorption of Cr(VI). The optimization parameters were agitation rate, work volume, pH and glucose concentration. Following the optimization of EPS production, the biofilm was used in the biosorption of hexavalent Cr from liquid solutions. Differences between the use of dead or active biomass and between the performance of zeolite in powder or in pellet form were also studied. The optimized EPS production allowed values of metal uptake between 2.72 mg/g(biosorbent) and 7.88 mg/g(biosorbent) for initial Cr(VI) concentrations of 20-60 mg/L. For an initial concentration of 20 mg/L, the optimal conditions of EPS production allowed an increase of 10% on the removal percentage of total Cr, and the use of zeolite as a powder rather than the pelleted form produced an increase of 46.5% in the removal percentage. For the initial concentration of 60 mg/L, the use of active biomass compared to dried biomass allowed a reduction of the time required for the total removal of Cr(VI) from 20 to 13 days.
Annals of Tropical Medicine and Parasitology. Dec, 2011 | Pubmed ID: 22325816
Ongoing transmission of lymphatic filariasis (LF) was assessed in five Samoan villages by measuring microfilaraemia (Mf), circulating filarial antigen (CFA) and antibody prevalence. Compared to the other villages, Fasitoo-Tai had a significantly higher Mf prevalence (3·2%), CFA prevalence (14·6%) and antibody prevalence in children (62·0%) (P<0·05). Puapua had a significantly lower CFA prevalence (2·5%), no detectable Mf-positive individuals and significantly low antibody prevalence in children (7·9%) (P<0·05). Siufaga, previously believed to be LF-free, recorded >1% CFA prevalence and a high antibody prevalence in children (46·6%). Overall, antibody prevalence in children appeared to reflect the transmission dynamics in the villages and, in Siufaga, identified an area of ongoing transmission. The Filariasis Cellabs Enzyme-Linked Immunosorbent Assay (CELISA), based on recombinant antigen Bm14, to detect antibodies, could potentially be a promising diagnostic tool for inclusion in future surveillance in the South Pacific.
Rivista Di Psichiatria. Sep-Dec, 2011 | Pubmed ID: 22322681
RIASSUNTO. Introduzione. Coloro che praticano la restrizione alimentare (RE) mostrano un'alternanza ricorrente di restrizione/eccesso nei confronti del cibo. Questo comportamento altalenante è stato recentemente messo in relazione con l'umore e il modello affettivo in generale. In questo contesto, si sostiene che la RE possa essere sensibile allo stress. Tuttavia, non ci sono prove sostanziali che dimostrino che la RE presenti modelli comportamentali o psicofisiologici che rivelano questa percezione. Scopo. Verificare se esiste una relazione nel comportamento da RE con all'interno di un paradigma empirico che influenzi l'alternanza premio/punizione. Metodo. 104 studentesse universitarie (31 RE e 73 di controllo) hanno costituito un gruppo sperimentale in cui, a seguito di alternanze premio/punizione, hanno scelto una opzione vantaggiosa. Risultati. È stata osservata un'interazione significativa tra la Scelta e il Gruppo A, rivelando che la frequenza di punizione inibisce l'opzione di risposta nella RE, indipendentemente dal vantaggio/svantaggio. Sebbene siano necessari ulteriori studi, i risultati rappresentano una prova preliminare che gli RE sono sensibili allo stress. Sono state discusse le implicazioni cliniche di questa scoperta.
Acta Gastroenterologica Latinoamericana. Dec, 2011 | Pubmed ID: 22292234
Toxicophoric and Metabolic in Silico Evaluation of Benzimidazole and Phenylbenzamide Derivatives with Potential Application As Anticancer Agents
Drug Metabolism Letters. Jan, 2012 | Pubmed ID: 22292473
Poor pharmacokinetics and toxicity are responsible for most drug candidate failures. In order to attempt to some degree of ADMET (Absorption, Distribution, Metabolism, Excrection and Toxicity) information, in silico predictions arise currently as an interesting alternative to evaluate prototypes during early stages of the drug design processes, especially for anticancer candidates that constitute a class of therapeutic agents that exhibit substantial toxicity. A benzimidazole and a phenylbenzamide derivatives, previously identified as novel anticancer lead compounds able to prevent DNA binding to hnRNP K protein, were evaluated in silico regarding their metabolic profile and toxicity potential in order to give insights to the design of drug candidates with an adequate pharmaceutical profile. Considering the structure of proposed metabolites for both molecules, the phenylbenzamide derivative seems to be a molecule with better pharmaceutic profile, since its possible metabolites present a milder degree of chemical structure toxic alerts than the benzimidazole derivative that can cause chromosome damage induced by the benzimidazole group. It would be desirable during optimization of the phenylbenzamide derivative to maintain these characteristics during generation of analogues with substituents that are not known as potent toxicophoric groups. For the benzimidazole derivative, if the toxic events are really severe as it seems, one possible strategy would be replace the benzimidazole ring system by bioisosteres with lower toxic potential, hoping to maintain or enhance biological activity.
Effect of the Antitumoral Alkylating Agent 3-bromopyruvate on Mitochondrial Respiration: Role of Mitochondrially Bound Hexokinase
Journal of Bioenergetics and Biomembranes. Feb, 2012 | Pubmed ID: 22322891
The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (ΔΨ(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt-HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system.
A Brief Report on Some Health Aspects of Rats Fed with Crescent Levels of Recombinant Chagasin, a Potential Plant Defense Protein
Anais Da Academia Brasileira De Ciencias. Feb, 2012 | Pubmed ID: 22323311
Chagasin may be considered a potential plant-incorporated protectant (PIP) protein due to its deleterious effects on insect pests. However, extensive safety studies with PIPâs are necessary before introducing them into the target plant. Thus, a short-term feeding trial in rats with high doses of r-chagasin was conducted to provide evidences about its safety. Three test diets containing casein + r-chagasin (0.25, 0.5 and 1% of total protein) were offered to rats (10 days). The test diets did not show adverse effects upon the development, organ weight, hematological parameters and serum protein profiles of rats, providing preliminary information on the safety of r-chagasin.
Arquivos Brasileiros De Cardiologia. Jan, 2012 | Pubmed ID: 22323330
This report describes a case of a 62 year-old man admitted for recurrent myocardial infarction and normal coronary arteries, caused by coronary embolism from aortic papillary fibroelastoma. Other conditions causing acute coronary syndrome and normal coronary arteries are discussed. A careful evaluation by transthoracic and transesophageal echocardiography is required in this clinical setting. Surgical excision of the tumor is safe and curative.
Clinical and Radiological Results Following Radial Osteotomy in Patients with Kienbock's Disease: Four- to 18-year Follow-up
The Journal of Bone and Joint Surgery. British Volume. Feb, 2012 | Pubmed ID: 22323690
Radial osteotomy is currently advocated for patients with Lichtman's stages II and IIIA of Kienböck's disease; its place in the treatment of patients with stage IIIB disease remains controversial. The purpose of this study was to evaluate the medium-term results of this procedure and to compare the outcome in patients with stage IIIB disease and those with earlier stages (II and IIIA). A total of 18 patients (18 osteotomies) were evaluated both clinically and radiologically at a mean follow-up of 10.3 years (4 to 18). Range of movement, grip strength and pain improved significantly in all patients; the functional score (Nakamura Scoring System (NSSK)) was high and self-reported disability (Disabilities of Arm, Shoulder and Hand questionnaire) was low at the final follow-up in all patients evaluated. Patients with stage IIIB disease, however, had a significantly lower grip strength, lower NSSK scores and higher disability than those in less advanced stages. Radiological progression of the disease was not noted in either group, despite the stage. Radial osteotomy seems effective in halting the progression of disease and improving symptoms in stages II, IIIA and IIIB. Patients with less advanced disease should be expected to have better clinical results.
Colloids and Surfaces. B, Biointerfaces. Jan, 2012 | Pubmed ID: 22326343
Since its discovery the therapeutic use of the pancreatic hormone amylin has been limited due to its poor water solubility and propensity for amyloid aggregation. We have entrapped the human amylin protein in polymeric nanoparticles, using a single emulsion-solvent evaporation method and investigated its effectiveness in the controlled release of the peptide. Typical preparations composed of poly-ɛ-caprolactone had a mean particle size of approximately 200nm, low polydispersity index, high protein entrapment efficiency (80%) and process yield (90%), and spherical and smooth surfaces. These nanoparticles presented a controlled release in vitro for approximately 240h. Pharmacological evaluation in vivo by subcutaneous administration in fasting mice demonstrated the bioactivity and effectiveness of the released human amylin, resulting in reduced glycemia lasting for at least 36h. These features indicate the potential for the use of a confined particulate system in the therapeutic controlled and sustained release of human amylin.
Anti-leishmanial Activity of Alkaloidal Extracts Obtained from Different Organs of Aspidosperma Ramiflorum
Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. Feb, 2012 | Pubmed ID: 22326547
The present study was designated to evaluate semi-quantitative antileishmanial activity of alkaloidal extracts that were obtained from 1g of different parts of Aspidosperma ramiflorum (leaves, roots, seeds, and stem barks). Alkaloidal extracts of barks and leaves presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis. It is known that compounds responsible for the antileishmanial activity in the alkaloidal extracts from A. ramiflorum are the monoterpenoid indole alkaloids ramiflorine A and ramiflorine B, therefore extracts obtained from different plant parts were analyzed by electrospray ionization mass spectrometry (ESI-MS) in order to evidence the presence of these bioactive alkaloids. Based on these findings, alkaloidal extract from leaves was fractionated on preparative thin-layer chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 18.5±6.5μg/ml and 12.63±5.52μg/ml, respectively). Our results are showing that alkaloidal extract from leaves is a promising alternative to the use of stem barks from A. ramiflorum.
Toxicity of Glycerol for the Stallion Spermatozoa: Effects on Membrane Integrity and Cytoskeleton, Lipid Peroxidation and Mitochondrial Membrane Potential
Theriogenology. Feb, 2012 | Pubmed ID: 22326587
Glycerol is, to date, the most widely used cryoprotectant to freeze stallion spermatozoa at concentrations between 2% and 5%. Cryoprotectant toxicity has been claimed to be the single most limiting factor for the success of cryopreservation. In order to evaluate the toxic effects of the concentrations of glycerol used in practice, stallion spermatozoa were incubated in Biggers Whitten and Whittingham (BWW) media supplemented with 0%, 0.5%, 1.5%, 2.5%, 3.5%, and 5% glycerol. In two additional experiments, a hyposmotic (75 mOsm/kg) and a hyperosmotic (900 mOsm/kg) control media were included. Sperm parameters evaluated included cell volume, membrane integrity, lipid peroxidation, caspase 3, 7, and 8 activation, mitochondrial membrane potential, and integrity of the cytoskeleton. Glycerol exerted toxicity at concentrations ≥ 3.5% and the maximal toxicity was observed at 5%. The actin cytoskeleton was especially sensitive to glycerol presence, inducing rapid F actin depolymerization at concentrations over 1.5%. The sperm membrane and the mitochondria were other structures affected. The toxicity of glycerol is apparently related to osmotic and nonosmotic effects. In view of our results the concentration of glycerol in the freezing media for stallion spermatozoa should not surpass 2.5%.
Effect of Cariogenic Biofilm Challenge on the Surface Hardness of Direct Restorative Materials in Situ
Journal of Dentistry. Feb, 2012 | Pubmed ID: 22326721
OBJECTIVES: The presence of cariogenic biofilm could result in surface degradation of composite and ionomeric restorative materials. Thus, this study evaluated in situ the alterations in the surface microhardness of these materials under biofilm accumulation and cariogenic challenge. METHODS: In a split-mouth, double-blind, cross-over study, 10 volunteers wore palatal intra-oral devices containing bovine enamel slabs restored with composite resin (CR - Z250) or resin-modified glass ionomer (RMGI - Vitremer). Two phases of 14days were carried out, one for each restorative material. In one side of the device, biofilm was allowed to accumulate under a plastic mesh, whereas in the opposing side, regular brushing was carried out 3 times/day with a dentifrice containing 1100μg F/g as NaF. A 20% sucrose solution was applied extra-orally 10×/day on each restored dental slab. Knoop microhardness was used to calculate the percentage of surface hardness loss (%SHL). RESULTS: All materials showed a decrease in surface hardness after the in situ period. The restorative materials presented the following average for %SHL: RMGI without biofilm accumulation=8.9 and with biofilm accumulation=25.6, CR without biofilm accumulation=14.7 and with biofilm accumulation=17.0. CONCLUSION: Biofilm accumulation and the presence of cariogenic challenge promoted faster degradation of ionomeric materials, but this was not observed for composite resin. CLINICAL SIGNIFICANCE: The oral environment affects the surface hardness of aesthetic restorative materials. Biofilm accumulation and cariogenic challenge promote surface degradation for ionomeric materials, but not for composite resin.
Effects of Therapeutic Pulsed Ultrasound and Dimethylsulfoxide Phonophoresis on Oxidative Stress Parameters After Injury Induced by Eccentric Exercise
Ultrasonics. Jan, 2012 | Pubmed ID: 22326779
INTRODUCTION: The aim of the study was to evaluate the effects of TPU together with DMSO on oxidative stress parameters after eccentric exercise. METHODS: Thirty and six animals were divided in control; eccentric exercise (EE); EE+saline gel 0.9%; EE+TPU 0.8W/cm(2); EE+DMSO gel; EE+TPU+DMSO gel and submitted to one 90-min downhill run (1.0kmh(-1)). TPU was used 2, 12, 24, 46h after exercise session and 48h after the animals were killed and the gastrocnemius muscles were surgically removed. Production of superoxide anion, creatine kinase (CK) levels, lipoperoxidation, carbonylation, and antioxidants enzymes were analyzed. RESULTS: Showed that TPU and gel-DMSO improved muscle healing. Moreover, superoxide anion production, TBARS level and protein carbonyls levels, superoxide dismutase and catalase activity were all decreased in the group TPU plus gel-DMSO. DISCUSSION: Our results show that DMSO is effective in the reduction of the muscular lesion and in the oxidative stress after eccentric exercise only when used with TPU.
A Novel and Efficient Epoxy/chitosan Cement Slurry for Use in Severe Acidic Environments of Oil Wells-Structural Characterization and Kinetic Modeling
Journal of Hazardous Materials. Jan, 2012 | Pubmed ID: 22326824
In this study, the biopolymer chitosan was used to synthesize a new epoxy/chitosan cement slurry. The features of the new slurry were evaluated in relation to a standard cement slurry (w/c=0.5). A kinetic study of the interaction epoxy/chitosan slurry/HCl was performed to simulate the use of the new slurry in environmental-friendly acidizing procedures of oil wells. The experimental data were well fitted to a three-parameter kinetic model. The analysis of the kinetic modeling suggests that surface reactions constitute the main interactions at the interface epoxy/chitosan-modified cement slurry/HCl. The characterization of the slurries was performed by FTIR, XRD, TG/DTG and solid-state reflectance spectroscopy. The results have pointed out that the main features of the new cement slurry were preserved, even after long-term contact with HCl in aqueous solution. The results of this study underline the excellent features of the new epoxy/chitosan-modified cement slurry for using in environmental-friendly acidizing procedures of oil wells.
Acute Electrophysiological Modulation of the Atria and Pulmonary Veins: Effects of Sympathetic and Parasympathetic Interaction on Atrial Fibrillation Inducibility
Revista Portuguesa De Cardiologia : Orgao Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal of Cardiology : an Official Journal of the Portuguese Society of Cardiology. Feb, 2012 | Pubmed ID: 22326990
Atrial fibrillation (AF) is a complex disease with multiple mechanisms, involving the interaction between the autonomic nervous system (ANS), electrophysiological properties of the atria and pulmonary veins (PVs), and vulnerability for AF. AIM: We assessed the effects of acute vagal (vagus_stim) and sympathetic stimulation (symp_stim) on atrial conduction, atrial and PV refractoriness and inducibility of AF in an in vivo rabbit model with preserved autonomic innervation. METHODS: An open-epicardial approach was used in 17 anesthetized and artificially ventilated New Zealand white rabbits. The ECG was recorded with bipolar subcutaneous electrodes placed in the four limbs. Electrograms were obtained with four monopolar electrodes placed epicardially along the atria, and a circular electrode adapted to the proximal PVs. The cervical vagus nerve and thoracic sympathetic trunk were stimulated with bipolar electrodes. Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs) and conduction times from the high-lateral right atrium (RA) to the high-lateral left atrium (LA) and PVs were quantified at baseline and during vagus_stim, symp_stim, or combined vagal and sympathetic stimulation (dual_stim). Burst pacing (50Hz, 10s), alone or combined with vagus_stim, symp_stim or dual_stim, was performed in the right (RAA) and left atrial appendage (LAA) and PVs to test for AF inducibility. RESULTS: At baseline, ERPs were higher in the LAA and there was a delay in the conduction time from RA to PV, compared to the mean activation time from RA to LA. During vagus_stim or dual_stim, ERP decreased significantly at all sites, and baseline interatrial activation times changed from 20±4ms to 30±10ms and 31±11ms, respectively (p<0.05). Symp_stim resulted in a significant decrease in ERPs only in the LAA, and a reduction of the interatrial interval to 16±11ms (p<0.05 vs baseline). AF inducibility ranged from 35% to 53% with baseline 50Hz pacing, 65% to 76% during vagus_stim or symp_stim, and 75% to 100% with dual_stim (p<0.05). AF duration increased significantly during ANS stimulation. In two-thirds of the animals with longer inducible AF, the arrhythmia ceased immediately after cessation of vagus_stim. CONCLUSIONS: In the fully innervated rabbit heart in vivo, acute ANS stimulation shortens atrial and PV refractoriness, and significantly changes atrial conduction times, promoting AF induction and prolonging the arrhythmia. This underscores the importance of acute variations in ANS tone and its interactions in the pathophysiology of AF.
The Leishmanicidal Flavonols Quercetin and Quercitrin Target Leishmania (Leishmania) Amazonensis Arginase
Experimental Parasitology. Feb, 2012 | Pubmed ID: 22327179
Polyamine biosynthesis enzymes are promising drug targets for the treatment of leishmaniasis, Chagas' disease and African sleeping sickness. Arginase, which is a metallohydrolase, is the first enzyme involved in polyamine biosynthesis and converts arginine into ornithine and urea. Ornithine is used in the polyamine pathway that is essential for cell proliferation and ROS detoxification by trypanothione. The flavonols quercetin and quercitrin have been described as antitrypanosomal and antileishmanial compounds, and their ability to inhibit arginase was tested in this work. We characterized the inhibition of recombinant arginase from Leishmania (Leishmania) amazonensis by quercetin, quercitrin and isoquercitrin. The IC(50) values for quercetin, quercitrin and isoquercitrin were estimated to be 3.8, 10 and 4.3μM, respectively. Quercetin is a mixed inhibitor, whereas quercitrin and isoquercitrin are uncompetitive inhibitors of L. (L.) amazonensis arginase. Quercetin interacts with the substrate l-arginine and the cofactor Mn(2+) at pH 9.6, whereas quercitrin and isoquercitrin do not interact with the enzyme's cofactor or substrate. Docking analysis of these flavonols suggests that the cathecol group of the three compounds interact with Asp129, which is involved in metal bridge formation for the cofactors Mn(A)(2+) and Mn(B)(2+) in the active site of arginase. These results help to elucidate the mechanism of action of leishmanicidal flavonols and offer new perspectives for drug design against Leishmania infection based on interactions between arginase and flavones.
In Vitro and in Vivo Efficacy of Aqueous Extract of Caryocar Brasiliense Camb. to Control Gastrointestinal Nematodes in Sheep
Parasitology Research. Feb, 2012 | Pubmed ID: 22327318
A major problem faced in sheep rearing has been the rapid acquisition of anthelminthic-resistant populations of gastrointestinal nematodes. In the search for alternatives, aqueous extract of the peel of Caryocar brasiliense was evaluated for larval development inhibition, egg-hatching inhibition, and fecal nematode egg count reduction in sheep. For in vivo analysis, the doses were calculated according to a 10% lethal dose derived from acute toxicity tests in mice, and the efficacy was evaluated for two periods following oral administration of the extract. Egg-hatching inhibition at concentrations of 15 and 7.5 mg/ml was significantly higher than observed in negative controls with distilled water. For larval development inhibition, all concentrations showed anthelminthic activity significantly higher than controls and were not significantly different from ivermectin treatment. The LC(90) of larval development inhibition was 53.19 mg/ml. In vivo analysis for first and second weeks after treatment found 32.2% and 33% anthelminthic efficacy, respectively.
Changes in Liver Proteome Expression of Senegalese Sole (Solea Senegalensis) in Response to Repeated Handling Stress
Marine Biotechnology (New York, N.Y.). Feb, 2012 | Pubmed ID: 22327442
The Senegalese sole, a high-value flatfish, is a good candidate for aquaculture production. Nevertheless, there are still issues regarding this species' sensitivity to stress in captivity. We aimed to characterize the hepatic proteome expression for this species in response to repeated handling and identify potential molecular markers that indicate a physiological response to chronic stress. Two groups of fish were reared in duplicate for 28 days, one of them weekly exposed to handling stress (including hypoxia) for 3 min, and the other left undisturbed. Two-dimensional electrophoresis enabled the detection of 287 spots significantly affected by repeated handling stress (Wilcoxon-Mann-Whitney U test, p < 0.05), 33 of which could be reliably identified by peptide mass spectrometry. Chronic exposure to stress seems to have affected protein synthesis, folding and turnover (40S ribosomal protein S12, cathepsin B, disulfide-isomerase A3 precursor, cell-division cycle 48, and five distinct heat shock proteins), amino acid metabolism, urea cycle and methylation/folate pathways (methionine adenosyltransferase I α, phenylalanine hydroxylase, mitochondrial agmatinase, serine hydroxymethyltransferase, 3-hydroxyanthranilate 3,4-dioxygenase, and betaine homocysteine methyltransferase), cytoskeletal (40S ribosomal protein SA, α-actin, β-actin, α-tubulin, and cytokeratin K18), aldehyde detoxification (aldehyde dehydrogenase 4A1 family and aldehyde dehydrogenase 7A1 family), carbohydrate metabolism and energy homeostasis (fatty acid-binding protein, enolase 3, enolase 1, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, aconitase 1, mitochondrial ATP synthase α-subunit, and electron-transfer flavoprotein α polypeptide), iron and selenium homeostasis (transferrin and selenium binding protein 1), steroid hormone metabolism (3-oxo-5-β-steroid 4-dehydrogenase), and purine salvage (hypoxanthine phosphoribosyltransferase). Further characterization is required to fully assess the potential of these markers for the monitoring of fish stress response to chronic stressors of aquaculture environment.
Cytoskeleton (Hoboken, N.J.). Feb, 2012 | Pubmed ID: 22328323
Microtubules or their subunits, tubulin dimers, interact with multiple components that contribute to intracellular metabolic pathways. Microtubules are required for insulin-dependent transport of glucose transporters (GLUT4) to the plasma membrane, they bind most glycolytic enzymes and are required for translation of the mRNA encoding hypoxia inducible factor -1α. Tubulin dimers bind the voltage dependent anion channel of the mitochondrial outer membrane; this channel functions in metabolite transport in and out of mitochondria. We hypothesize that tubulin partitioning between dimer and polymer pools regulates multiple steps in metabolism, where metabolic output is greatest when both tubulin dimers and microtubule polymers are present and reduced by drug treatments that disrupt this normal balance. Experimental evidence from these drug-induced changes in tubulin dimer/polymer partitioning supports our model for several metabolic steps. Signal transduction pathways that stabilize or destabilize microtubules can shift the normal ratio between unpolymerized and polymerized tubulin dimers, and one downstream consequence of this shift in tubulin partitioning could be a change in metabolic output. © 2012 Wiley Periodicals, Inc.
Immunophenotypic Alterations in Resident Immune Cells and Myocardial Fibrosis in the Aging Rhesus Macaque (Macaca Mulatta) Heart
Toxicologic Pathology. Feb, 2012 | Pubmed ID: 22328408
The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age, which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r = .6522, p < .0001 and r = .4704, p = .005, respectively). When divided into young (mean = 2.8 years), middle-aged (mean = 17.5 years), and advanced age (mean = 29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p < .0001). HAM-56 expression decreased significantly in the advanced age cohort (p = .0021). The expression of CD8, CD163, and DC-SIGN correlated positively with age (r = .3999, p = .0191; r = .5676, p = .0005; r = .5245, p = .0014, respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis.
Oral Rehabilitation of Severely Worn Dentition Using an Overlay for Immediate Re-establishment of Occlusal Vertical Dimension
Gerodontology. Mar, 2012 | Pubmed ID: 22329361
doi: 10.1111/j.1741-2358.2010.00372.x Oral rehabilitation of severely worn dentition using an overlay for immediate re-establishment of occlusal vertical dimension The aim of this study was to describe the treatment used in an elderly patient presenting with bruxism and dental erosion, with good gingival health and bone support, but with decreased occlusal vertical dimension (OVD). The oral rehabilitation of elderly patients presenting with bruxism in association with tooth erosion has been a great challenge for dentists. The loss of OVD, the presence of occlusal instability and the absence of an effective anterior guide due excessive dental wear, can damage stomatognathic system (SS) biology, the function and the aesthetics. In the first treatment stage, an overlay removable partial denture (ORPD) was fabricated for the immediate re-establishment of function and aesthetics. After a 2-month follow up, with the patient presenting no symptoms, a second rehabilitation stage was accomplished, with fixed and removable prostheses. Oral rehabilitation with an ORPD was able to re-establish the SS biology, but a correct diagnosis and treatment plan are essential for success. The ORPD is a non-invasive and reversible restoring modality for general dentists that allow the re-establishment of the patient's immediate aesthetics and function at low cost.
Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012 | Pubmed ID: 22329736
The first stages of the electrocrystalization of (Perylene)2[Au(mnt)2] salt from dichloromethane on gold, platinum and highly orientated pyrolytic graphite (HOPG) were investigated by cyclic voltammetry, atomic force microscopy and XPS in order to understand the determinant factors for nucleation and crystal growth. The crystal growth occurs from adsorbed films, of dithiolate on gold or platinum, and of perylene on HOPG, after homogeneous nucleation and it is controlled by the low diffusion of the species towards the growing surface.
S-Phase Fraction and Ploidy As Predictive Markers in Primary Disease and Recurrence of Papillary Thyroid Carcinoma
Clinical Endocrinology. Feb, 2012 | Pubmed ID: 22329804
OBJECTIVE: To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC). DESIGN: A large prospective study with long-term follow-up (median, 117 months). PATIENTS: Two series of patients with primary PTC (n=305) and lymph node recurrence metastasis (LNM) (n=39) were involved in the study. MEASUREMENTS: Patient's age and gender, histological variant, pTNM staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses. RESULTS: Seventeen (5.6%) primary tumours and 5 (12.8%) LNMs were aneuploid, while mean SPF was 2.7% and 3.7%, respectively (p=0.022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (p=0.051) in relation to overall survival. In multivariate analysis, older age (≥ 48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; p=0.011). CONCLUSION: The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC. © 2012 Blackwell Publishing Ltd.
Two for One: Cyclic AMP Mediates the Anti-inflammatory and Anti-spasmodic Properties of the Non-anesthetic Lidocaine Analog JMF2-1
European Journal of Pharmacology. Feb, 2012 | Pubmed ID: 22329902
Inhalation of JMF2-1, an analog of lidocaine with reduced anesthetic activity, prevents airway contraction and lung inflammation in experimental asthma models. We sought to test if the JMF2-1 effects are a consequence of increased intracellular cAMP levels in asthma cell targets, such as smooth muscle cells and T cells. Functional effect of JMF2-1 on carbachol-induced contraction of intact or epithelial-denuded rat trachea was assessed in conventional organ baths. cAMP was quantified by radioimmunoassay in cultured guinea pig tracheal smooth muscle cells, as well as lymph node cells from BALB/c mice, exposed to JMF2-1. We found that JMF2-1 (0.1-1mM) concentration-dependently inhibited epithelium-intact tracheal ring contraction induced by carbachol challenge. The antispasmodic effect remained unaltered following epithelium removal or pretreatment with NG-nitro-L-arginine methyl ester (100μM), but it was clearly sensitive to 9-(tetrahydro-2-furyl) adenine (SQ22,536, 100μM), an adenylate cyclase inhibitor. JMF2-1 (300 and 600μM) also dose-dependently increased cAMP intracellular levels of both cultured airway smooth muscle cells and T lymphocytes. This effect was consistently abrogated by SQ22,536 and reproduced by forskolin in both systems. JMF2-1 induced apoptosis of anti-CD3 activated T cells in a mechanism sensitive to zIETD, indicating that JMF2-1 mediates caspase-8-dependent apoptosis. Furthermore, forskolin also inhibited anti-CD3 induced T cell proliferation and survival. Our results suggest that JMF2-1 inhibits respiratory smooth muscle contraction as well as T cell proliferation and survival through enhancement of intracellular cAMP levels. These findings may help to explain the anti-inflammatory and antispasmodic effects of JMF2-1 observed in previous studies.
Medicine and Science in Sports and Exercise. Feb, 2012 | Pubmed ID: 22330022
PURPOSE: This study examined effects of a behavioral weight management intervention on body image (evaluative and investment dimensions), and explored the potential mediating role of structured and lifestyle physical activity (PA). METHODS: Longitudinal randomized controlled trial, including a 1-year behavior change intervention and a 2-year follow-up (225 women; 37.6±7 yr; 31.5±4.1 kg/m BMI). Statistical analyses comprised mixed-design ANOVAs with repeated measures, bivariate/partial correlations, and mediation analyses. RESULTS: Body image improved considerably in both groups, favoring the intervention group (small to moderate effect sizes: .03 - .05), but began to deteriorate from 12 to 24 months, especially in the intervention group. Consequently, at 24 months, between-group differences were small and did not reach significance. Yet, levels of body dissatisfaction and dysfunctional investment remained below initial values (for both groups). Results were similar for both body image dimensions. Structured PA (at 12 and 24 months) and lifestyle PA (at 24 months) were positively associated with (r > -.25, p < .05) and partially mediated body image improvements, especially in the investment component (95% CI of -1.88 to -.27 for structured PA at 12 months; 95% CI of -1.94 to -.21 for lifestyle PA at 24 months). In general, change in evaluative body image was not mediated by exercise participation, appearing more dependent on weight change. CONCLUSIONS: These findings highlight the importance of PA as a contributing factor in the improvement of body image in overweight/obese women, mainly by reducing excessive salience of appearance to one's life and self. Lifestyle PA may also be a valid option, particularly in the long-term. Exercise might provide a buffer against body image deterioration overtime, favoring lasting weight loss maintenance.
European Heart Journal Cardiovascular Imaging. Feb, 2012 | Pubmed ID: 22330231
Optical coherence tomography (OCT) is a high-resolution imaging technique with great versatility of applications. In cardiology, OCT has remained hitherto as a research tool for characterization of vulnerable plaques and evaluation of neointimal healing after stenting. However, OCT is now successfully applied in different clinical scenarios, and the introduction of frequency domain analysis simplified its application to the point it can be considered a potential alternative to intravascular ultrasound for clinical decision-making in some cases. This article reviews the use of OCT for assessment of lesion severity, characterization of acute coronary syndromes, guidance of intracoronary stenting, and evaluation of long-term results.
Molecules (Basel, Switzerland). 2012 | Pubmed ID: 22330429
The essential oils obtained from leaves of Piper duckei and Piper demeraranum by hydrodistillation were analyzed by gas chromatography-mass spectrometry. The main constituents found in P. demeraranum oil were limonene (19.3%) and β-elemene (33.1%) and in P. duckei oil the major components found were germacrene D (14.7%) and trans-caryophyllene (27.1%). P. demeraranum and P. duckei oils exhibited biological activity, with IC(50) values between 15 to 76 μg mL-1 against two Leishmania species, P. duckei oil being the most active. The cytotoxicity of the essential oils on mice peritoneal macrophage cells was insignificant, compared with the toxicity of pentamidine. The main mono- and sesquiterpene, limonene (IC(50) = 278 μM) and caryophyllene (IC(50) = 96 μM), were tested against the strains of Leishmania amazonensis, and the IC(50) values of these compounds were lower than those found for the essential oils of the Piper species. The HET-CAM test was used to evaluate the irritation potential of these oils as topical products, showing that these oils can be used as auxiliary medication in cases of cutaneous leishmaniasis, with less side effects and lower costs.
An Isoniazid Analogue Promotes Nanoparticle-Mycobacterium Tuberculosis Interactions and Enhances Bacterial Killing by Macrophages
Antimicrobial Agents and Chemotherapy. Feb, 2012 | Pubmed ID: 22330919
Nano-enabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis (Mtb) and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation as well as inhibits Mtb growth by enhancing drug intracellular bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular Mtb and cell-free bacteria indicating that NPs directly interact with the bacterium. Together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.
Mitigation by Vitamin C of the Genotoxic Effects of Nicotine in Mice, Assessed by the Comet Assay and Micronucleus Induction
Mutation Research. Feb, 2012 | Pubmed ID: 22331007
Nicotine has been reported to cause acute toxicity and to present long-term risks, such as chromosomal damage and genetic instability. The genotoxicity of nicotine may be mediated partly by an oxidative mechanism. We have evaluated the effects of the antioxidant vitamin C on nicotine-induced genotoxicity in mice. The comet assay and the micronucleus test were used to assess the effects of nicotine (15mg/kg) at different exposure times (2, 4, and 24h in the comet assay; 24h in the micronucleus test). Pretreatment with vitamin C 24h before nicotine exposure strongly protected mice against nicotine-induced DNA damage.
[The Brazilian Oral Health Survey (SBBrasil 2003): Determining Sample Weights and Structural Information]
Cadernos De Saúde Pública / Ministério Da Saúde, Fundação Oswaldo Cruz, Escola Nacional De Saúde Pública. Feb, 2012 | Pubmed ID: 22331151
This is an article on probability sampling written to describe the methods used to calculate and calibrate sample weights of the Brazilian Oral Health Survey (SBBrasil 2003) and identify sample structural variables. It presents an overview of the efforts made to retrieve information from the records used to select the sample units in the sampled municipalities and describes the main problems observed with the survey's database, that acted as constraints tocal culating the natural sample weights and identifying primary sampling units and selection strata. It compares weighted sample estimates with previously published unweighted sample descriptive statistics, concluding that the oral health of the Brazilian population was better than previously disclosed.
[Suicide Risk and Health Risk Behavior Among Youth Between the Ages of 18 and 24 Years: a Descriptive Study]
Cadernos De Saúde Pública / Ministério Da Saúde, Fundação Oswaldo Cruz, Escola Nacional De Saúde Pública. Feb, 2012 | Pubmed ID: 22331156
The aim of this study was to assess suicide risk and risk behavior in young people. A cross-sectional study in the urban area of Pelotas, Rio Grande do Sul State, Brazil was performed using systematic sampling with young people between the ages of 18 to 24 years. We measured the risk of suicide (MINI), behavior (YRBSS), abuse/substance dependence (ASSIST) and socioeconomic status (ABEP). Data was analyzed using SPSS software. The sample consisted of 1,560 young people and the prevalence of suicide risk was 8.6%. Suicide risk was associated with: having suffered an accident that required a visit to the emergency room (p = 0.011), fighting (p = 0.016), carrying a weapon (p = 0.001) and carrying a firearm (p < 0.001), substance abuse/dependence (p < 0.001), not having used a condom during the last sexual relationship (p = 0.025), not having a steady partner (p < 0.001) and having sex with five or more people (p = 0.018). Young people that present risk behavior also represent a suicide risk.
[Iodine Deficiency and Associated Factors in Infants and Preschool Children in an Urban Community in the Semiarid Region of Minas Gerais State, Brazil, 2008]
Cadernos De Saúde Pública / Ministério Da Saúde, Fundação Oswaldo Cruz, Escola Nacional De Saúde Pública. Feb, 2012 | Pubmed ID: 22331160
The aim of this study was to evaluate the prevalence of iodine deficiency in children aged 6 to 71 months in Novo Cruzeiro, Minas Gerais State, Brazil. A total of 475 children, allocated by stratified probability sampling, were analyzed with respect to the iodine concentrations in the salt consumed by the family and urinary iodine. Iodine deficiency was verified in 34.4% of the children, of which 23.5% showed slight deficiency, 5.9% moderate and 5% serious deficiency. A difference in the distribution of iodine deficiency was observed between the urban and the rural environments (p < 0.001) where average urinary iodine concentrations of 150.8 and 114.3µg/L respectively were found. A greater proportion of iodine deficiency was observed among children where the proportion of iodine in the salt consumed was below the recommended level. Although expressive, iodine deficiency in Novo Cruzeiro is not a public health problem according to World Health Organization (WHO), The limitrophe distribution of the urinary iodine associated with low iodine levels in salt suggests that efforts to control this deficiency are not yet complete.
Transgene-mediated Cosuppression and RNA Interference Enhance Germ-line Apoptosis in Caenorhabditis Elegans
Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012 | Pubmed ID: 22331911
Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation.
Clinical and Experimental Pharmacology & Physiology. Feb, 2012 | Pubmed ID: 22332899
Myostatin (MSTN) has been implicated in metabolic adaptation to physiological stimuli, such as physical exercise, which is linked to improved glucose homeostasis. The aim of the present study was to evaluate the influence of exercise on the expression of MSTN, MSTN receptors (ActRIIB and ALK4), and Follistatin (FS) in muscle and fat of streptozotocin-induced diabetic rats. Control and diabetic animals were randomly assigned to a swimming training group (EC and ED) and a sedentary group (SC and SD). Exercising animals swam for 45 minutes at 09:00 and 17:00 hours, 5 day week(-1) , for 4 weeks. MSTN, ActRIIB, ALK4 and FS mRNA was quantified by real time RT-PCR. MSTN and FS mRNA expression increased in muscle and subcutaneous fat of SD compared to SC. The expression of ActRIIB mRNA increased in SD compared to SC in muscle, mesenteric fat and brown adipose tissue (BAT). Expression of ALK4 mRNA increased in SD compared to SC in BAT. After training, MSTN and ActRIIB were lower in EC compared to SC in BAT. MSTN mRNAexpression increased in mesenteric fat and FS mRNA expression decreased in muscle, mesenteric and subcutaneous fat and BAT in ED compared to SD. ALK4 mRNA expression was lower in BAT of ED compared to BAT of SD. These results indicate that MSTN, its receptors and FS expression change in both muscle and fat of diabetic rats and their expressions can be modulated by exercise in diabetes. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
Translating Guidelines Into Practice: Ventilator-Associated Pneumonia Prevention Strategies in an Acute Rehabilitation Unit
Dimensions of Critical Care Nursing : DCCN. Mar, 2012 | Pubmed ID: 22333722
Ventilator-associated pneumonia has significant mortality (33%-50%). The highest risk of ventilator-associated pneumonia is early in mechanical ventilation with an increase in morbidity and mortality seen with late-onset ventilator-associated pneumonia. Prevention strategies have been recommended for acute care facilities, but there is lack of evidence-based data and recommendations for acute rehabilitation units. A multidisciplinary team designed an evidence-based ventilator-associated pneumonia prevention policy based on the Institute for Healthcare Improvement ventilator bundle. Education of rehabilitation staff and implementation of the protocol were done. Results showed that the ventilator-associated pneumonia rate decreased from 7.5 to 0 per 1000 patient ventilator days. Translating evidence-based guidelines into practice can be accomplished using a multidisciplinary team.
Neurological Research. Feb, 2012 | Pubmed ID: 22333942
BACKGROUND: Vasospasm is a frequent complication of subarachnoid hemorrhage (SAH), implicated in poor outcome, and prediction of its occurrence might be important on the therapeutic approach of this condition. Brain oxygenation in aneurysmal SAH was prospectively monitored during surgery in 28 patients, using brain tissue oxygen pressure (PbtO(2)), studying its association with the occurrence of post-operative vasospasm, detected by transcranial Doppler. METHODS: PbtO(2) monitoring was performed during surgery of 28 patients with aneurysmal SAH, using a polarographic microcatheter (Licox; GMS, Kiel, Germany), inserted into the cerebral tissue. The aneurysms were localized in the anterior communicating artery (AcoA) complex (eight cases), in the posterior communicating artery (Pcom) origin (seven cases), and in the middle cerebral artery (MCA) bifurcation (13 cases). Basal PbtO(2) values, obtained immediately before application of temporary or definitive clips, were studied according to age, clinical status and CT findings. The association between the basal values and the occurrence of increased blood flow velocity in the post-operative transcranial Doppler (TCD vasospasm) was investigated. RESULTS: Post-operative TCD vasospasm developed in 13 patients, all of them with basal values inferior to 10 mmHg. PbtO(2) basal value was significantly lower in cases that developed TCD vasospasm. This association was independent of age, clinical status, or CT findings. CONCLUSION: The finding of low intraoperative basal PbtO(2) values may be an indicator for a high risk of occurrence of post-operative TCD vasospasm in cases of aneurysmatic SAH.
MEDICC Review. Jan, 2012 | Pubmed ID: 22334109
INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results. KEYWORDS Diagnosis, laboratory techniques and procedures, antibodies, HIV-2, Western blot, enzyme-linked immunosorbent assay, algorithm, Cuba.
Observation of Electrochemically Controlled Quantum Interference in a Single Anthraquinone-Based Norbornylogous Bridge Molecule
Angewandte Chemie (International Ed. in English). Feb, 2012 | Pubmed ID: 22334514
A single-molecular switch based on the anthraquinone/hydroanthraquinone redox reaction is reported. A single norbornyl-anthraquinone unit can be switched between a low-conducting and a high-conducting form using electrochemical gating. The potential range, upon which the conductance enhancement is observed, can be varied using different pH values of the electrolyte.
Operative Dentistry. Feb, 2012 | Pubmed ID: 22335301
SUMMARY The objective of this study was to determine whether the hardness of etch-and-rinse adhesives may be affected by the pretreatment of acid-etched dentin with potassium oxalate desensitizer. Unerupted human third molars were cut into crown segments by removing the occlusal enamel and roots. The pulp chamber of these crown segments was connected to a syringe barrel filled with phosphate-buffered saline so that the moisture of dentin was maintained during the bonding procedures. Three etch-and-rinse adhesives-two two-step systems (Adper Single Bond 2 [SB], One-Step [OS]) and one three-step system (Adper Scotchbond Multi-Purpose [MP])-were applied to acid-etched dentin that had been treated (experimental groups) or not (control groups) with potassium oxalate (BisBlock). The Knoop hardness (KHN) of adhesives was taken at different sites of the outer surface of the adhesive-bonded dentin. The KHN of the three tested adhesives applied to acid-etched dentin treated with potassium oxalate was significantly lower than that exhibited by the respective controls (not treated with oxalate; p<0.05). Regardless of the adhesive, the treatment with potassium oxalate reduced the adhesives' KHN (p<0.05), with the OS system exhibiting the lowest KHN compared with the MP and SB systems.
Dietary Bioaccumulation of Perfluorophosphonates and Perfluorophosphinates in Juvenile Rainbow Trout: Evidence of Metabolism of Perfluorophosphinates
Environmental Science & Technology. Feb, 2012 | Pubmed ID: 22335432
The perfluorophosphonates (PFPAs) and perfluorophosphinates (PFPiAs) are high production volume chemicals that have been observed in Canadian surface waters and wastewater environments. To examine whether their occurrence would result in contamination of organisms in aquatic ecosystems, juvenile rainbow trout (Oncorhynchus mykiss) were separately exposed to a mixture of C6, C8, and C10 monoalkylated PFPAs and a mixture of C6/C6, C6/C8, and C8/C8 dialkylated PFPiAs in the diet for 31 days, followed by 32 days of depuration. Tissue distribution indicated preferential partitioning to blood and liver. Depuration half-lives ranged from 3 to 43 days and increased with the number of perfluorinated carbons present in the chemical. The assimilation efficiencies (α, 7-34%) and biomagnification factors (BMFs, 0.007-0.189) calculated here for PFPAs and PFPiAs were lower than those previously observed for the perfluorocarboxylates (PFCAs) and perfluorosulfonates (PFSAs) in the same test organism. Bioaccumulation was observed to decreased in the order of PFSAs > PFCAs > PFPAs of equal perfluorocarbon chain length and was dependent on the charge of the polar headgroup. Bioaccumulation of the PFPiAs was observed to be low due to their rapid elimination via metabolism to the corresponding PFPAs. Here, we report the first observation of an in vivo cleavage of the carbon-phosphorus bond in fish, as well as, the first in vivo biotransformation of a perfluoroalkyl acid (PFAA). As was previously observed for PFCAs and PFSAs, none of the BMFs determined here for the PFPAs and PFPiAs were greater than one, which suggests PFAAs do not biomagnify from dietary exposure in juvenile rainbow trout.
Cochrane Database of Systematic Reviews (Online). 2012 | Pubmed ID: 22336786
Previous systematic reviews comparing stapled and handsewn colorectal anastomosis that are available in the medical literature have not shown either technique to be superior. An update of this systematic review was performed to find out if there are any data that properly answer this question.
Transcription-mediated Amplification (TMA) for the Assessment of Viremia in Hemodialysis Patients with Hepatitis C
Journal of Medical Virology. Apr, 2012 | Pubmed ID: 22337298
The diagnosis of hepatitis C virus (HCV) infection in hemodialysis patients is difficult particularly due to the presence of intermittent viremia. The aims of this study were: (a) to determine the prevalence of intermittent viremia in hemodialysis patients with anti-HCV antibodies who tested negative for HCV RNA by PCR at the first evaluation and (b) to evaluate the contribution of the transcription-mediated amplification method (TMA) to the diagnosis of viremia in the PCR-negative samples. One hundred and six patients with anti-HCV antibodies and an initial negative result for HCV RNA by PCR were included. An additional sample was collected for a second HCV RNA test by PCR after a minimum interval of 3 months and a positive result characterized intermittent viremia. HCV RNA was investigated by TMA in the PCR-negative sample of patients with intermittent viremia, and in the most recent sample from patients with PCR-negative results in both determinations. Intermittent viremia was observed in 60/106 (57%) patients (57% men; age: 45 ± 10 years). Fifty-one of the 60 negative samples from patients with intermittent viremia and 29/46 double-negative patients were tested by TMA. This assay detected viremia in 20/51 (39%) samples of intermittent viremia and in 2/29 (7%) of double-negative samples. The results showed that intermittent viremia is frequent in hemodialysis patients who tested negative for HCV RNA by PCR. Therefore, a second HCV RNA test is necessary for all HCV RNA-negative patients. The TMA assay appears to be the best first screening test for viremia in this population. J. Med. Virol. 84:596-600, 2012. © 2011 Wiley Periodicals, Inc.
The Journal of Craniofacial Surgery. Jan, 2012 | Pubmed ID: 22337393
ABSTRACT: Treatment of facial trauma sequelae is a complex and challenging process. There is still controversy over suitable materials for orbital wall reconstruction. This study evaluated calcium phosphate cement (CPC) implants manufactured by rapid prototyping in the repair of orbital wall defects secondary to trauma. Computed tomographic scans of 5 patients were used for surgery planning and production of CPC implants. Implants were used to restore orbital wall anatomy, ocular alignment, and facial contour. Benefits resulting from the use of implants, such as a reduced operating time, patient response to biomaterial implantation, biomaterial integrity and stability, and patient satisfaction with treatment, were analyzed qualitatively. Our results suggest that CPC is an effective and safe material for orbital reconstruction because of its biocompatibility and easy production and placement.
The Journal of Craniofacial Surgery. Jan, 2012 | Pubmed ID: 22337469
ABSTRACT: The peripheral ossifying fibroma (POF) is a common gingival growth usually arising from the interdental papilla. The anterior maxilla is the most common location of involvement. The etiology and pathogenesis of POF remains unknown. Some investigators consider it a neoplastic process, whereas others argue that it is a reactive process; in either case, the lesion is thought to arise from cells in the periodontal ligament. Trauma or local irritants, such as dental plaque, calculus, microorganisms, masticatory force, ill-fitting dentures, and poor quality restorations, have been implicated in the etiology of POF. The recommended treatment is the excisional biopsy; however, it can leave a defect if the procedure is not followed by a subepithelial connective tissue graft. The main objective of this article was to present a clinical case of excisional biopsy of a POF followed by a subepithelial connective tissue graft to correct the defect caused by the biopsy. The biopsy defect was satisfactorily repaired, and the lesion has not recurred after 6 years of follow-up.
Journal of the Royal Society, Interface / the Royal Society. Feb, 2012 | Pubmed ID: 22337627
Using sequence data to infer population dynamics is playing an increasing role in the analysis of outbreaks. The most common methods in use, based on coalescent inference, have been widely used but not extensively tested against simulated epidemics. Here, we use simulated data to test the ability of both parametric and non-parametric methods for inference of effective population size (coded in the popular BEAST package) to reconstruct epidemic dynamics. We consider a range of simulations centred on scenarios considered plausible for pandemic influenza, but our conclusions are generic for any exponentially growing epidemic. We highlight systematic biases in non-parametric effective population size estimation. The most prominent such bias leads to the false inference of slowing of epidemic spread in the recent past even when the real epidemic is growing exponentially. We suggest some sampling strategies that could reduce (but not eliminate) some of the biases. Parametric methods can correct for these biases if the infected population size is large. We also explore how some poor sampling strategies (e.g. that over-represent epidemiologically linked clusters of cases) could dramatically exacerbate bias in an uncontrolled manner. Finally, we present a simple diagnostic indicator, based on coalescent density and which can easily be applied to reconstructed phylogenies, that identifies time-periods for which effective population size estimates are less likely to be biased. We illustrate this with an application to the 2009 H1N1 pandemic.
Magnetic Resonance in Chemistry : MRC. Feb, 2012 | Pubmed ID: 22337691
Low-field (1) H NMR was used in this work for the analysis of mixtures involving crude oils and water. CPMG experiments were performed to determine the transverse relaxation time (T(2) ) distribution curves, which were computed by the inverse Laplace transform of the echo decay data. The instrument's ability of quantifying water and petroleum in biphasic mixtures following different methodologies was tested. For mixtures between deionized water and petroleum, one achieved excellent results, with root mean squared error of cross-validation (RMSECV) of 0.8% for a regression between the water content (wt %) and the relative area of the water peak in the T(2) distribution curve, or a standard deviation of 0.9% for the relationship between the water content and the relative water peak area, corrected by the relative hydrogen index of the crude. In the case of biphasic mixtures of Mn(2+) -doped water and crude oils, the best result of RMSECV = 1.6% was achieved by using the raw magnetization decay data for a partial least squares regression. Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Infection in Developing Countries. 2012 | Pubmed ID: 22337847
The diarrhea associated with gastroenteritis is a major cause of morbidity and mortality worldwide, affecting mainly infants. The characterization of both viral and bacterial agents associated with gastroenteritis can establish policies for surveillance, prevention and treatment of infections. Group A rotaviruses are the major infectious agent associated with dehydration in children, followed by pathotypes of Escherichia coli. There are three main types of clinical infections caused by E. coli strains that have acquired virulence genes: (i) enteric and diarrheal diseases, (ii) urinary tract infections, and (iii) sepsis and meningitis.
Journal of Periodontology. Feb, 2012 | Pubmed ID: 22309175
Background: Periodontitis is an inflammatory process caused by a specific group of microorganisms, resulting in the destruction of the tooth-supporting tissue and the resorption of the alveolar bone. Therefore, periodontitis has been considered a risk factor for pre-eclampsia, since infection is one of the factors involved in the etiology and pathogenesis of pre-eclampsia. The aim of the present study was to determine whether periodontitis is a risk factor for pre-eclampsia and to identify other possible risk factors. Methods: A case-control study was carried out with 574 puerperae under care at the university hospital at the Universidade Federal de Pernambuco in the city of Recife (Northeastern Brazil). Data collection was preceded by a training exercise and a pilot study. Biological and socioeconomic data were collected along with medical and dental records. A periodontal examination was performed on all dental elements in order to determine probing depth and gingival recession. The association between periodontitis and pre-eclampsia was first adjusted for the variables within each block and then, in the final multivariate model it was then adjusted for the variables of all blocks. Results: The multivariate logistic regression analysis showed that, after adjustment for other risk factors, periodontitis remained an independent risk factor for pre-eclampsia (OR(adjusted) = 8.60; CI 3.92 to 18.88; p < 0.001 and 2.03, 95%-CI: 1.43 - 2.90; p < 0.001, when using the CDC/AAP definition). Conclusion: The results suggest that within the studied population, periodontitis was a risk factor for pre-eclampsia.
Retrosplenial Cortex is Involved in Analgesia Induced by 2- but Not 100-Hz Electroacupuncture in the Rat Tail-Flick Test
Journal of Acupuncture and Meridian Studies. Feb, 2012 | Pubmed ID: 22309907
This study examined whether or not the antinociceptive effect of 2- or 100-Hz electroacupuncture (EA) depends on the integrity of the retrosplenial cortex (RSC). Rats were taken for determination of tail-flick latency before and after injection of saline or 2% lidocaine (0.25μl) into the retrosplenial cortex (RSC) bilaterally. Five minutes later, they were submitted to a 20-minute period of 2Hz, 100Hz, or sham EA at the Zusanli and Sanyinjiao acupoints bilaterally, and tail-flick latency was measured within 30 seconds after the end of stimulation and at 5-minute intervals for up to 30 minutes. EA at a frequency of either 2 or 100Hz induced a strong and long-lasting inhibition of the tail-flick reflex in rats treated with saline (0.25μl) injected into the RSC. The analgesia produced by 2-Hz EA lasted for a shorter time in lidocaine-treated rats. By contrast, RSC impairment did not change the analgesic effect of 100Hz EA. The integrity of the RSC is implicated in the duration of analgesia induced by low-frequency EA but is not essential for the analgesic effects evoked by high-frequency EA.
Progress in Neuro-psychopharmacology & Biological Psychiatry. Jan, 2012 | Pubmed ID: 22310225
Treatment of major depression, posttraumatic stress disorder and other psychopathologies with antidepressants can be associated with improvement of the cognitive deficits related to these disorders. Although the mechanisms of these effects are not completely elucidated, alterations in the extinction of aversive memories are believed to play a role in these psychopathologies. We have recently verified that female rats present low levels of extinction when submitted to the plus-maze discriminative avoidance task. In the present study, female rats were treated long term with clinically used antidepressants (fluoxetine, nortriptyline or mirtazapine) and subjected to the plus-maze discriminative avoidance task to evaluate learning, memory, extinction and anxiety-related behaviors as well as behavioral despair in the forced swimming test. All groups learned the task and exhibited retrieval. Chronic treatment with fluoxetine (but not with the other antidepressants tested) increased extinction of the discriminative task. In the forced swimming test, the animals treated with fluoxetine and mirtazapine showed decreased immobility duration. In conclusion, fluoxetine potentiated extinction, while both fluoxetine and mirtazapine were effective in ameliorating depressive-like behavior in the forced swimming test, suggesting a possible dissociation between the effects on mood and the extinction of aversive memories in female rats.
Assessing a Bioremediation Strategy in a Shallow Coastal System Affected by a Fish Farm Culture - Application of GIS and Shellfish Dynamic Models in the Rio San Pedro, SW Spain
Marine Pollution Bulletin. Feb, 2012 | Pubmed ID: 22310375
An integrated multi-trophic aquaculture assessment for Pacific oyster (Crassostrea gigas) aquaculture as a bioremediation strategy in areas impacted by fish farm effluents in Rio San Pedro was assessed by combining geographic information system with carrying capacity models. Sites of 0.44km(2) were evaluated considering constraints; physical factors, growth and survival factors, environmental quality factors, water and sediment quality criteria, factor suitability ranges, and Multi-Criteria Evaluation. Isleta and Flamenco are promising sites for oyster production, and Dorada is of marginal interest. Carbon and nitrogen removal from the water by algae and through detritus filtration was estimated. The biodeposition of organic material from longline leases was found to have little negative impact on sediment. The eutrophication results indicate that phytoplankton removal had a positive impact on water quality at the Dorada. This case study quantified the direct profitability and bioremediative environmental service advantages that fish-shellfish farms can have relative to fish monocultures.
Simulium (Psilopelmia) Virescens, a New Black-fly Species (Diptera: Simuliidae) from the Southwestern Region of the State of Bahia, Brazil
Memórias Do Instituto Oswaldo Cruz. Feb, 2012 | Pubmed ID: 22310543
The last-instar larva, pupa, male and female of Simulium virescens sp. nov. are described and illustrated. This species has a peculiar larva, which has an elongated head capsule and light-green colour. The first thoracic segment has tubercle on its dorsal region and the third thoracic segment has one pair of tubercles; the first to the fourth abdominal segments have one pair of tubercles on each segment. Until now this new species had only been collected at the type locality, which is on the middle stretch of the Correntina River in the southwestern portion of the state of Bahia, Brazil. Females were voraciously biting humans during the field work. This new species represents the second species of Simulium(Psilopelmia) in Brazil and the first registered outside of the Brazilian Amazon Region.
American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. Feb, 2012 | Pubmed ID: 22311059
OBJECTIVE: This study aimed to assess the effect of Transcutaneous Electrical Nerve Stimulation (TENS) on pain, nausea, and emesis in patients submitted to surgery for laparoscopic cholecystectomy. DESIGN: A clinical single-masked randomized study assessed patients submitted to laparoscopic cholecystectomy, who were divided into two groups: placebo TENS (G1) and active TENS (G2). The intensity of pain was determined using the visual analog scale and the 11-point Verbal Numerical Scale, applied to the participants before (M1) and 30 mins after (M2) TENS. A conventional biphasic square pulse TENS current was used, at a frequency of 150 Hz and a pulse width of 75 μsecs. The relative risks of the occurrence of nausea and emesis were calculated for groups G1 and G2. Determination of the effect of TENS on analgesia used the Mann-Whitney U test, at a significance level of 5%, to compare independent samples (Dif G1 and Dif G2). RESULTS: The relative risk of nausea and/or emesis was 2.17 times greater for patients from the placebo group. Pain evaluation using the visual analog scale showed median differences between M1 and M2 of 0.4 and 2.4 for groups G1 and G2, respectively. The values obtained using Verbal Numerical Scale were 0.7 (G1) and 3.0 (G2). The active TENS significantly reduced postoperative pain compared with the placebo (P < 0.016). CONCLUSIONS: Active TENS promoted significant postoperative pain relief, and fewer complaints of nausea and emesis, in patients submitted to laparoscopic cholecystectomy surgery.
Silver Nanoparticles: Influence of Stabilizing Agent and Diameter on Antifungal Activity Against Candida Albicans and Candida Glabrata Biofilms
Letters in Applied Microbiology. Feb, 2012 | Pubmed ID: 22313289
Aim: The purpose of this work was to evaluate the size-dependent antifungal activity of different silver nanoparticles (SN) colloidal suspensions against Candida albicans and Candida glabrata mature biofilms. Methods and Results: The research presented herein used SN of three different average sizes (five, 10 and 60 nm), which were synthesized by the reduction of silver nitrate through sodium citrate and which were stabilized with ammonia or polyvinylpyrrolidone. Minimal inhibitory concentration (MIC) assays were performed using the microdilution methodology. The antibiofilm activity of SN was determined by total biomass quantification (by crystal violet staining) and colony forming units enumeration. MIC results showed that all SN colloidal suspensions were fungicidal against the tested strains at very low concentrations (0.4-3.3 μg ml(-1) ). With regard to biomass quantification, SN colloidal suspensions were very effective only against C. glabrata biofilms, achieving biomass reductions around 90% at a silver concentration of 108 μg ml(-1) . In general, all SN suspensions promoted significant log(10) reduction of the mean number of cultivable biofilm cells after exposure to silver concentrations at or higher than 108 μg ml(-1) . Moreover, the results showed that the particle size and the type of stabilizing agent used did not interfere in the antifungal activity of SN against Candida biofilms. Conclusion: This study suggests that SN have antifungal therapeutic potential, but further studies are still required namely regarding formulation and delivery means. Significance and Impact of Study: SN may contribute to the development of new strategies for the improvement of oral health and quality of life particularly of the complete denture wearers. © 2012 The Authors Letters in Applied Microbiology © 2012 The Society for Applied Microbiology.
The Efficacy of Daily Bathing with Chlorhexidine for Reducing Healthcare-Associated Bloodstream Infections: A Meta-analysis
Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. Mar, 2012 | Pubmed ID: 22314063
Design. Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies to assess the efficacy of daily bathing with chlorhexidine (CHG) for prevention of healthcare-associated bloodstream infections (BSIs). Setting. Medical, surgical, trauma, and combined medical-surgical intensive care units (ICUs) and long-term acute care hospitals. Participants. Inpatients. Methods. Data on patient population, diagnostic criteria for BSIs, form and concentration of topical CHG, incidence of BSIs, and study design were extracted. Results. One randomized controlled trial and 11 nonrandomized controlled trials reporting a total of 137,392 patient-days met the inclusion criteria; 291 patients in the CHG arm developed a BSI over 67,775 patient-days, compared with 557 patients in the control arm over 69,617 catheter-days. CHG bathing resulted in a reduced incidence of BSIs: the pooled odds ratio using a random-effects model was 0.44 (95% confidence interval, 0.33-0.59; [Formula: see text]). Statistical heterogeneity was moderate, with an I(2) of 58%. For the subgroup of studies that examined central line-associated BSIs, the odds ratio was 0.40 (95% confidence interval, 0.27-0.59). Conclusions. Daily bathing with CHG reduced the incidence of BSIs, including central line-associated BSIs, among patients in the medical ICU. Further studies are recommended to determine the optimal frequency, method of application, and concentration of CHG as well as the comparative effectiveness of this strategy relative to other preventive measures available for reducing BSIs. Future studies should also examine the efficacy of daily CHG bathing in non-ICU populations at risk for BSI.
The Role of Pro/anti-inflammatory Adipokines on Bone Metabolism in NAFLD Obese Adolescents: Effects of Long-term Interdisciplinary Therapy
Endocrine. Feb, 2012 | Pubmed ID: 22315014
To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.
Proteins Derived from Latex of C. Procera Maintain Coagulation Homeostasis in Septic Mice and Exhibit Thrombin- and Plasmin-like Activities
Naunyn-Schmiedeberg's Archives of Pharmacology. Feb, 2012 | Pubmed ID: 22315016
The proteins derived from the latex (LP) of Calotropis procera are well known for their anti-inflammatory property. In view of their protective effect reported in the sepsis model, they were evaluated for their efficacy in maintaining coagulation homeostasis in sepsis. Intraperitoneal injection of LP markedly reduced the procoagulation and thrombocytopenia observed in mice infected with Salmonella; while in normal mice, LP produced a procoagulant effect. In order to understand its mechanism of action, the LP was subjected to ion-exchange chromatography, and the three subfractions (LP(PI), LP(PII), and LP(PIII)) thus obtained were tested for their proteolytic effect and thrombin- and plasmin-like activities in vitro. Of the three subfractions tested, LP(PII) and LP(PIII) exhibited proteolytic effect on azocasein and exhibited procoagulant effect on human plasma in a concentration-dependent manner. Like trypsin and plasmin, these subfractions produced both fibrinogenolytic and fibrinolytic effects that were mediated through the hydrolysis of the Aα, Bβ, and γ chains of fibrinogen and α-polymer and γ-dimer of fibrin clot, respectively. This study shows that the cysteine proteases present in the latex of C. procera exhibit thrombin- and plasmin-like activities and suggests that these proteins have therapeutic potential in various conditions associated with coagulation abnormalities.
International Urology and Nephrology. Feb, 2012 | Pubmed ID: 22315155
PURPOSE: To evaluate the relative efficiency of leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg in relation to the reduction in serum testosterone, regarding the levels of castration. MATERIALS AND METHODS: We evaluated prospectively 60 randomized patients with advanced prostate carcinoma, with indication for hormone blockade. The patients were divided into 3 groups of 20: Group (1) received leuprolide 3.75 mg; Group (2) received leuprolide 7.5 mg; and Group (3) received goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum testosterone were evaluated in two moments: before the treatment and 3 months after the treatment. RESULTS: The patients' ages were similar within the three groups, with a median of 72, 70, and 70 in groups 1, 2, and 3, respectively. Of the patients that received leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, 26.3, 25, and 35%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 50 ng/dl. And 68.4, 30, and 45%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 20 ng/dl. CONCLUSIONS: There were no statistically significant differences in the levels of castration when comparing leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, altogether. When compared in groups of two, there was a statistically significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg, the latter presented better results in reaching castration levels, cutoff ≤ 20 ng/dl. The importance of this difference, however, must be measured with caution, since the comparison of the three groups simultaneously did not reach the established significance level, even though it came close.
Epidemiology (Cambridge, Mass.). Mar, 2012 | Pubmed ID: 22317818
Revista Portuguesa De Cardiologia : Orgao Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal of Cardiology : an Official Journal of the Portuguese Society of Cardiology. Feb, 2012 | Pubmed ID: 22317862
Automated Analysis of Lidocaine and Its Metabolite in Plasma by In-tube Solid-phase Microextraction Coupled with LC-UV for Pharmacokinetic Study
Journal of Separation Science. Feb, 2012 | Pubmed ID: 22318808
A sensitive, selective, and reproducible in-tube solid-phase microextraction and liquid chromatographic (in-tube SPME/LC-UV) method for determination of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in human plasma has been developed, validated, and further applied to pharmacokinetic study in pregnant women with gestational diabetes mellitus (GDM) subjected to epidural anesthesia. Important factors in the optimization of in-tube SPME performance are discussed, including the draw/eject sample volume, draw/eject cycle number, draw/eject flow rate, sample pH, and influence of plasma proteins. The limits of quantification of the in-tube SPME/LC method were 50 ng/mL for both metabolite and lidocaine. The interday and intraday precision had coefficients of variation lower than 8%, and accuracy ranged from 95 to 117%. The response of the in-tube SPME/LC method for analytes was linear over a dynamic range from 50 to 5000 ng/mL, with correlation coefficients higher than 0.9976. The developed in-tube SPME/LC method was successfully used to analyze lidocaine and its metabolite in plasma samples from pregnant women with GDM subjected to epidural anesthesia for pharmacokinetic study.
Gyroxin and Its Biological Activity: Effects on CNS Basement Membranes and Endothelium and Protease-activated Receptors
Current Medicinal Chemistry. Jan, 2012 | Pubmed ID: 22320302
Gyroxin is a glycoprotein isolated from rattlesnake venom, with known thrombin-like serine protease properties and behavioral action in the CNS. The mechanism of the latter has eluded experimenters for three decades. In this paper about the in vitro chick retina we demonstrate an excitotoxic CNS action of Gyroxin by observing retinal Intrinsic Optical Signals (IOS). These show sudden dynamic changes in the intact tissue due to gyroxin action. The very fast kinetics of this response precludes deep tissue penetration by the protein, a mechanism of tissue response described here for the first time. At nanomolar concentrations, Gyroxin alters profoundly the optical profiles of retinal spreading depression waves (RSDs), suggesting modulation of ionic transport and metabolism. This effect is reversible in contrast with the acute cell lysis induced with gyroxin pulses at higher concentration. Because there may be more than one target of Gyroxine at the retinal inner limiting membrane, additional biochemical assays were performed to study a possible Na/K-ATPase blockade and PAR receptor activation. We conclude that the Gyroxin interaction with basement membranes of CNS and endothelium triggers conformational phase transitions at basement membranes, with multiple functional consequences.
Grape Juice Concentrate Modulates P16 Expression in High Fat Diet-induced Liver Steatosis in Wistar Rats
Toxicology Mechanisms and Methods. Apr, 2012 | Pubmed ID: 22320862
Purpose: The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. Methods: Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. Results: The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. Conclusion: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats.
A Comparison of Two Distinct Murine Macrophage Gene Expression Profiles in Response to Leishmania Amazonensis Infection
BMC Microbiology. Feb, 2012 | Pubmed ID: 22321871
ABSTRACT: BACKGROUND: The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite. RESULTS: The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells. CONCLUSION: The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells.
Structural Transitions Induced by Shear Flow and Temperature Variation in a Nonionic Surfactant/water System
Journal of Colloid and Interface Science. Jan, 2012 | Pubmed ID: 22321990
In this study, we investigate structural transitions of tetraethylene glycol monohexadecyl ether (C(16)E(4)) in D(2)O as a function of shear flow and temperature. Via a combination of rheology, rheo-small-angle neutron scattering and rheo-small-angle light scattering, we probe the structural evolution of the system with respect to shear and temperature. Multi-lamellar vesicles, planar lamellae, and a sponge phase were found to compete as a function of shear rate and temperature, with the sponge phase involving the formation of a new transient lamellar phase with a larger spacing, coexisting with the preceding lamellar phase within a narrow temperature-time range. The shear flow behavior of C(16)E(4) is also found to deviate from other nonionic surfactants with shorter alkyl chains (C(10)E(3) and C(12)E(4)), resembling to the C(16)E(7) case, of longer chain.
PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS
Molecular & Cellular Proteomics : MCP. Feb, 2012 | Pubmed ID: 22322096
Proteomic studies of post-translational modifications (PTMs) by metal affinity or antibody-based methods often employ data-dependent analysis, providing rich datasets that consist of randomly sampled identified peptides due to the dynamic response of the mass spectrometer. This can complicate the primary goal of programs for drug development, mutational analysis, and kinase profiling studies, which is to monitor how multiple nodes of known, critical signaling pathways are affected by a variety of treatment conditions. Cell Signaling Technology (CST) has developed an immunaffinity-based LC-MS/MS method, called PTMScan Direct, for multiplexed analysis of these important signaling proteins. PTMScan Direct enables the identification and quantification of hundreds of peptides derived from specific proteins in signaling pathways or specific protein types. Cell lines, tissues, or xenografts can be used as starting material. PTMScan Direct is compatible with both SILAC and label-free quantification. Current PTMScan Direct reagents target key nodes of many signaling pathways (PTMScan Direct: Multipathway), serine/threonine kinases, tyrosine kinases, and the Akt/PI3K pathway. Validation of each reagent includes score filtering of MS/MS assignments, filtering by identification of peptides derived from expected targets, identification of peptides homologous to expected targets, minimum signal intensity of peptide ions, and dependence upon presence of the reagent itself compared to a negative control. The Multipathway reagent was used to study sensitivity of human cancer cell lines to receptor tyrosine kinase inhibitors, and showed consistent results with previously published studies. The Ser/Thr Kinases reagent was used to compare relative levels of kinase-derived phosphopeptides in mouse liver, brain, and embryo, showing tissue-specific activity of many kinases including Akt and PKC family members. PTMScan Direct will be a powerful quantitative method for elucidation of changes in signaling in a wide array of experimental systems, combining the specificity of traditional biochemical methods with the high number of data points and dynamic range of proteomic methods.
Anthelminthic Efficacy of Banana Crop Residues on Gastrointestinal Nematodes of Sheep: in Vitro and in Vivo Tests
Parasitology Research. Feb, 2012 | Pubmed ID: 22322388
Resistance to anthelminthics is common due to intensive and incorrect use. In searching for alternatives, extracts of banana plant were evaluated for egg hatching inhibition and fecal egg count reduction of sheep nematodes. Aqueous extracts of the leaf, pseudostem, and heart of the banana plant cv. Prata anã were tested at concentrations of 0.31, 0.62, 1.25, 2.5, 5.0, and 10.0 mg ml(-1) in egg hatching inhibition tests. For in vivo analysis, aqueous extracts were evaluated at dosages calculated according to the 10% lethal dose derived from acute toxicity testing in mice. Efficacy was evaluated at two time periods following oral administration. For the banana extracts at 2.5 mg ml(-1), egg hatching was significantly fewer than the negative control, with an LC(50) and LC(90) of 0.19 and 0.84 mg ml(-1), respectively. In vivo analysis for weeks 1 and 2 following a single treatment with aqueous leaf extract showed 33.1% and 32.5% anthelminthic efficacy, respectively. Further research on higher dosages with more frequent administration is needed to evaluate the potential for utilizing banana plant residues in gastrointestinal nematode control.
Environmental Monitoring and Assessment. Feb, 2012 | Pubmed ID: 22322406
The main objective of this work was to quantify and characterize the major indoor air contaminants present in different stages of a municipal WWTP, including microorganisms (bacteria and fungi), carbon dioxide, carbon monoxide, hydrogen sulfide ammonia, formaldehyde, and volatile organic compounds (VOCs). In general, the total bacteria concentration was found to vary from 60 to >52,560 colony-forming units (CFU)/m(3), and the total fungi concentration ranged from 369 to 14,068 CFU/m(3). Generally, Gram-positive bacteria were observed in higher number than Gram-negative bacteria. CO(2) concentration ranged from 251 to 9,710 ppm, and CO concentration was either not detected or presented a level of 1 ppm. H(2)S concentration ranged from 0.1 to 6.0 ppm. NH(3) concentration was <2 ppm in most samples. Formaldehyde was <0.01 ppm at all sampling sites. The total VOC concentration ranged from 36 to 1,724 μg/m(3). Among the VOCs, toluene presented the highest concentration. Results point to indoor/outdoor ratios higher than one. In general, the highest levels of airborne contaminants were detected at the primary treatment (SEDIPAC 3D), secondary sedimentation, and sludge dehydration. At most sampling sites, the concentrations of airborne contaminants were below the occupational exposure limits (OELs) for all the campaigns. However, a few contaminants were above OELs in some sampling sites.
Bowman-Birk Inhibitors, Proteasome Peptidase Activities and Colorectal Pre Neoplasias Induced by 1,2-dimethylhydrazine in Swiss Mice
Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Feb, 2012 | Pubmed ID: 22326805
Bowman-Birk inhibitors (BBIs) are protein molecules containing two inhibitory domains for enzymes similar to trypsin and chymotrypsin. Interest in these inhibitors arose from their properties against the cancer chemically induced by 1,2-dimethylhydrazine (DMH). In this study the effect of two BBI preparations (from Glycine max and Macrotyloma axillare) were evaluated for the prevention of colorectal neoplasia induced by intraperitoneal injections of DMH, given at a dose of 30mg/kg, during 12weeks. Mice treated with DMH presented histopathological alterations consistent with tumor development, augmented CD44 expression and increased proteasome peptidase activities. Lysosomal fractions, obtained from the intestines, were chromatographed in a Sepharose-BBI column and increased activity for trypsin and chymotrypsin-like proteases recovered from DMH-treated animals. In parallel, mice treated for eight weeks with BBIs showed a decrease in the chymotrypsin and trypsin-like proteasome activities compared to animals fed on normal diet. For the groups receiving simultaneous treatment with DMH and BBIs, dysplasic lesions were not observed and proteasome peptidase activities were similar to the control group after the 24th week. These results suggest that the mechanism by which BBIs could prevent the appearance of pre neoplastic lesions is associated with inhibition of both the lysosomal and proteasome-dependent proteolytic pathways.
Olfactory Acuity is Associated with Mood and Function in a Pilot Study of Stable Bipolar Disorder Patients
Bipolar Disorders. Feb, 2012 | Pubmed ID: 22329478
Hardy C, Rosedale M, Messinger JW, Kleinhaus K, Aujero N, Silva H, Goetz RR, Goetz D, Harkavy-Friedman J, Malaspina D. Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients. Bipolar Disord 2012: 14: 109-117. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder. Methods: We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM-IV bipolar disorder patients and 44 control subjects. Results: The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = -0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p = 0.024) and social fear (r = 0.610, p = 0.046). Conclusions: Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex-stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.
Spatial and Temporal Abundance of Three Sylvatic Yellow Fever Vectors in the Influence Area of the Manso Hydroelectric Power Plant, Mato Grosso, Brazil
Journal of Medical Entomology. Jan, 2012 | Pubmed ID: 22308793
Human biting catches of sylvatic yellow fever (SYF) vectors were conducted at eight stations in the influence area of the Manso hydroelectric power plant (Central Brazil) in sampling campaigns every 2 mo from July 2000 to November 2001. In total, 206 individuals were captured and classified as one of three species important for the transmission of SYF in Mato Grosso state: Haemagogus (Haemagogus) janthinomys (Dyar, 1921); Haemagogus (Conopostegus) leucocelaenus (Dyar & Shannon, 1924); and Sabethes (Sabethoides) chloropterus (Humboldt, 1819). The highest vector abundance was observed during the rainy season (November through March) and SYF vectors were present in all sampling points throughout the year, mainly in riparian and shadowed transitional forests at shadowed ramps.
Mitral Regurgitation During a Myocardial Infarction - New Predictors and Prognostic Significance at Two Years of Follow-up
Acute Cardiac Care. Feb, 2012 | Pubmed ID: 22296621
Aims: Ischemic Mitral Regurgitation (MR) has early prognostic impact in Myocardial Infarction (MI). Its medium-term importance, especially of mild MR, has not been established. Purpose: to determine new clinical/analytical predictors of MR in MI-patients and establish its prognostic value during two-year follow-up [endpoints: mortality, decompensated heart failure (dHF)].Methods and Results: 796 patients admitted for MI (age 68.8±13.4, 63.2% males, 44.6% STEMI). Data: Admission analytical study, risk scores, coronariography, pre-discharge echocardiogram. Patients followed for two years. Clinical/analytical predictors of pre-discharge MR assessed. Predictive model for presence of pre-discharge MR included GRACE for intra-hospital mortality [IHM](OR=1.008, p<0.001), glomerular filtration rate (GFR)[OR=0.993, p=0.048], admission haemoglobin (OR=0.84, p=0.003). In univariate analysis, moderate-severe MR predicted 2-year mortality (OR=3.32, p<0.001), but not dHF. Two year mortality rate was proportional to severity of pre-discharge MR. Mild MR (vs. no MR) associated with higher risk for 2-year mortality (OR=2.04, p=0.014) and re-admission for dHF (OR=2.55, p=0.001). Predictive model for 2-year mortality included MR severity (OR=1.42, p=0.033) and GRACE for IHM (OR=1.023, p<0.001).Conclusion: GRACE score for IHM, GFR and admission haemoglobin independently predicted risk for pre-discharge MR. MR, including its milder form, was an independent predictor of 2-year mortality, adding prognostic power to GRACE score.
Extra Corporeal Membrane Oxygenation As Right Heart Support Following Left Ventricular Assist Device Placement: A New Cannulation Technique
Heart, Lung & Circulation. Jan, 2012 | Pubmed ID: 22296942
Extracorporeal membrane oxygenation is an established treatment for acute respiratory failure, or low cardiac output syndrome. This can be veno-venous, in which de-oxygenated blood is drained from the venous system and oxygenated before being returned to the venous system, and veno-arterial where the re-oxygenated venous blood is returned to the arterial system. Haemorrhage, sepsis and thrombo-embolism are common and potentially lethal complications. Left ventricular assist devices are a continually evolving technology, that may be used as a bridge to transplantation or destination therapy in end-stage cardiac failure. The VentrAssist™ left ventricular assist device is a small implantable, continuous flow centrifugal pump, that is controlled and powered by a percutaneous lead. However, in these patients, right heart failure may present as an acute event following weaning from cardiopulmonary bypass (CPB), or post-operatively in the intensive care unit. Patients who do not respond to inotropes and pulmonary vasodilators may need a right ventricular assist device (RVAD). We report a successful case of right heart assist extra corporeal membrane oxygenation used as temporary right heart support in combination with a VentrAssist™ left ventricular assist device. The use of right heart assist extra corporeal membrane oxygenation to help a failing right heart during left ventricular assist device placement is not new, however, our technique describes a novel method of cannulation of the femoral vein and pulmonary trunk via a tunnelled vascular tube graft, which allows the chest to be closed whilst on right heart support, and decannulation to proceed without resternotomy. This technique has also been used successfully subsequent to this.
Applied Investigation on the Interaction of Hazardous Elements Binding on Ultrafine and Nanoparticles in Chinese Anthracite-derived Fly Ash
The Science of the Total Environment. Mar, 2012 | Pubmed ID: 22297247
A multifaceted instrumental approach was employed to determine the chemistry and mineralogy of pulverized-coal-combustion fly ashes from two Chinese power plants. Techniques included traditional optical microscopy, X-ray diffraction, and chemical analysis along with a variety of electron beam methods. The aim is to demonstrate and bring together the wide variety of procedures dealing with F as the key element of concern, and determining its location in the mineral nanoparticles. The Hg content of the Anwen (Songzao coalfield) fly ashes is higher than that of the Diandong (East Yunnan) fly ashes, possibly owing to the greater C and Cl in the Anwen fly ashes. Both fly ash sources contain a variety of amorphous and nano-crystalline trace-element-bearing particles, both associated with multi-walled carbon nanotubes and as particles independent of carbons.
Comparative Study of Tramadol Combined with Dexamethasone and Diclofenac Sodium in Third-molar Surgery
Journal of Cranio-maxillo-facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. Jan, 2012 | Pubmed ID: 22297271
The aim of this randomized, double-blind clinical trial was to investigate the effect of preemptive analgesia with a combination of tramadol+dexamethasone or tramadol+diclofenac sodium. The study included 30 patients (age range: 16-30years), who were randomly assigned to 2 groups by the split-mouth method. Postoperative pain was assessed with a visual analogue scale at 4, 6, 12, 24, and 48h postoperatively (p.o.h.). Swelling was measured at 48p.o.h. Maximal interincisor distance was measured at 48p.o.h. and 7 postoperative days (p.o.d.). Significant differences in postoperative pain intensity were detected between the drug combinations at 4, 6, and 12p.o.h., suggesting the importance of preemptive analgesia. Patients treated with tramadol+dexamethasone showed lower pain scores compared to the tramadol+diclofenac sodium combination, larger postoperative mouth opening, and less swelling. The tramadol+dexamethasone combination also was more effective than tramadol+diclofenac sodium at reducing inflammation.
The Entirely Carbohydrate Immunogen Tn-PS A1 Induces a Cancer Cell Selective Immune Response and Cytokine IL-17
Cancer Immunology, Immunotherapy : CII. Feb, 2012 | Pubmed ID: 22297566
The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; α-D-GalpNAc-ONH(2)) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti-PS A1 sera.
Medicine and Science in Sports and Exercise. Jan, 2012 | Pubmed ID: 22297803
PURPOSE: Exposure to diesel exhaust particles results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of chronic aerobic exercise on the pulmonary response to diesel exhaust particles have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to diesel exhaust particles. METHODS: BALB/c mice were subjected to aerobic exercise 5x/week for 5 weeks, concomitantly with exposure to diesel exhaust particles (DEP; 3 mg/mL; 10μL/mouse). The levels of exhaled nitric oxide, reactive oxygen species (ROS), cellularity, IL-6 and TNF-alpha were analyzed in BALF, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1beta, KC and TNF-alpha in lung parenchyma was evaluated with immunohistochemistry. The levels of IL-1beta, KC and TNF-alpha were also evaluated in serum. RESULTS: Aerobic exercise inhibited the DEP-induced increase in the levels of ROS (p<0.05), exhaled nitric oxide (p<0.01), total (p<0.01) and differential cells (p<0.01), IL-6 and TNF-alpha levels in BALF (p<0.05), the level of neutrophils (p<0.001), collagen density in lung parenchyma (p<0.05), the levels of IL-6, KC and TNF-alpha in plasma (p<0.05), and the expression of IL-1beta, KC and TNF-alpha by leukocytes in the lung parenchyma (p<0.01). CONCLUSION: We conclude that chronic aerobic exercise presents protective effects in a mouse model of DEP-induced lung inflammation. Our results indicate a need for human studies that evaluate the pulmonary responses to aerobic exercise chronically performed in polluted areas.
Dermatology Online Journal. 2012 | Pubmed ID: 22301044
Dermatophytic and non-dermatophytic onychomycosis (NDM) was indistinguishable clinically in our case series. Making a clinical diagnosis of onychomycosis without mycology is the routine practice in Sri Lanka. The prevalence of NDM (45.8%) was very high in our patient population, followed by yeasts (34.1%); dermatophyte infection made up only 20%. Therefore, the treatment of onychomycosis with griseofulvin seems futile. Close contact with soil, the habit of walking barefoot, frequent emersion of hands in water, and a hot, humid climate partly explain the variation in causative pathogens in this case series.
Periodontal Disease-Associated Compensatory Expression of Osteoprotegerin Is Lost in Type 1 Diabetes Mellitus and Correlates with Alveolar Bone Destruction by Regulating Osteoclastogenesis
Cells, Tissues, Organs. Feb, 2012 | Pubmed ID: 22301390
Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects of PD and DM1 enhance bone destruction, confirms the importance of the RANKL signaling pathway in bone destruction in DM1 in animal models and suggests the existence of alternative mechanisms potentiating bone degradation in PD.
Platelet-activating Factor Receptor Plays a Role in the Pathogenesis of Graft-versus-host Disease by Regulating Leukocyte Recruitment, Tissue Injury, and Lethality
Journal of Leukocyte Biology. Feb, 2012 | Pubmed ID: 22301794
PAF is a potent lipid mediator involved in several manifestations of acute inflammation, including leukocyte influx, leukocyte interaction with endothelium, and production of inflammatory cytokines. The present study evaluated the relevance of PAFR for the pathogenesis of acute GVHD using a model of adoptive transfer of splenocytes from WT or PAFR(-/- )C57BL/6J to B6D2F1 mice. Mice, which received PAFR(-/- )splenocytes or treatment with the PAFR antagonist, showed reduced clinical signs of disease and no mortality. In GVHD mice receiving PAFR(-/-) splenocytes, there was deceased bacterial translocation and tissue injury. Furthermore, production of proinflammatory cytokines and chemokines (TNF-α, IFN-γ, CCL2, CCL3, and CCL5) and accumulation of CD8(+) cells in intestine and liver were reduced in mice transplanted with the PAFR(-/-) splenocyte. Mechanistically, an absence or pharmacological blockade of PAFR was associated with decreased rolling and adhesion of leukocytes to the mesenteric microcirculation, as assessed by intravital microscopy. Despite decreased GVHD, there was maintained GVL activity when PAFR(-/-) leukocytes were transferred into WT mice. In conclusion, PAFR on donor leukocytes plays a critical role in GVHD by mediating leukocyte influx and cytokine production in target tissues. PAFR antagonist may potentially be useful in the treatment of GVHD in bone marrow-transplanted patients.
Reduction of Acute Hepatic Damage Induced by Acetaminophen After Treatment with Diphenyl Diselenide in Mice
Toxicologic Pathology. Feb, 2012 | Pubmed ID: 22301948
In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure.
The Dependence of α-tocopheroxyl Radical Reduction by Hydroxy-2,3-diarylxanthones on Structure and Micro-environment
Organic & Biomolecular Chemistry. Mar, 2012 | Pubmed ID: 22302132
The flavonoid quercetin is known to reduce the α-tocopheroxyl radical (˙TocO) and reconstitute α-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH), exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study repair of ˙TocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ˙TocO, though repair depends strongly on the micro-environment. In cationic cetyltrimethylammonium bromide (CTAB) micelles, 30% of ˙TocO radicals are repaired at a rate constant of ∼7.4 × 10(6) M(-1) s(-1) by XH9 compared to 1.7 × 10(7) M(-1) s(-1) by ascorbate. Water-soluble Trolox (TrOH) radicals (˙TrO) are restored by XH9 in CTAB (rate constant ∼3 × 10(4) M(-1) s(-1)) but not in neutral TX100 micelles where only 15% of ˙TocO are repaired (rate constant ∼4.5 × 10(5) M(-1) s(-1)). In basic aqueous solutions ˙TrO is readily reduced by deprotonated XH9 species leading to ionized XH9 radical species (radical pK(a)∼10). An equilibrium is observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [˙X9,H(+)/XH9] couple at pH 11, lower than the 250 mV for the [˙TrO,H(+)/TrOH] couple. A comparable value (100 mV) has been determined by cyclic voltammetry measurements.
Biomechanical Testing of Fracture Fixation Constructs: Variability, Validity, and Clinical Applicability
The Journal of the American Academy of Orthopaedic Surgeons. Feb, 2012 | Pubmed ID: 22302446
Biomechanical testing of fracture fixation implants is crucial in preclinical evaluation and in comparing new devices with standard devices. Many variables must be considered when planning and implementing a biomechanical in vitro experiment. The type of test selected (eg, load-to-failure, stiffness, cyclic fatigue) depends on the research question being asked. For example, cyclic fatigue testing attempts to replicate clinical situations; thus, the load magnitudes and directions and the number of cycles should be decided accordingly. Most important, each bone and region of bone experiences specific in vivo forces based on muscular and other forces. Debate persists regarding whether cadaver or synthetic bone is optimal. The use of either material in biomechanical testing should be carefully considered and justified in the context of the study hypothesis. Appropriate study design is the main factor that affects the clinical applicability of the findings and the accuracy of the conclusions.
Journal of Thrombosis and Thrombolysis. Feb, 2012 | Pubmed ID: 22298244
Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients.
The Journal of Biological Chemistry. Feb, 2012 | Pubmed ID: 22298775
The Forkhead transcription factor FoxO1 inhibits through its expression in osteoblasts β-cell proliferation, insulin secretion and sensitivity. At least part of the FoxO1 metabolic functions result from its ability to suppress the activity of osteocalcin, an osteoblast-derived hormone favoring glucose metabolism and energy expenditure. In searching for mechanisms mediating the metabolic actions of FoxO1 we focused on ATF4, because this transcription factor also affects glucose metabolism through its expression in osteoblasts. We show here that FoxO1 co-localizes with ATF4 in the osteoblast nucleus, and physically interacts with and promotes the transcriptional activity of ATF4. Genetic experiments demonstrate that FoxO1 and ATF4 cooperate to increase glucose levels and decrease glucose tolerance. These effects result from a synergistic effect of the two transcription factors to suppress the activity of osteocalcin through upregulating expression of the phosphatase catalyzing osteocalcin inactivation. As a result, insulin production by β-cells and insulin signaling in the muscle, liver and white adipose tissue is compromised and fat weight increases by the FoxO1/ATF4 interaction. Taken together these observations demonstrate that FoxO1 and ATF4 cooperate in osteoblasts to regulate glucose homeostasis.
Influenza A/H1N1 Vaccination of Patients with SLE: Can Antimalarial Drugs Restore Diminished Response Under Immunosuppressive Therapy?
Rheumatology (Oxford, England). Jan, 2012 | Pubmed ID: 22298793
Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens.Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination.Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09).Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.Trial registration. www.clinicaltrials.gov, NCT01151644.
Solid Lipid Nanoparticles (SLN) - Based Hydrogels As Potential Carriers for Oral Transmucosal Delivery of Risperidone: Preparation and Characterization Studies
Colloids and Surfaces. B, Biointerfaces. Jan, 2012 | Pubmed ID: 22293602
Two different solid lipid nanoparticles (SLN)-based hydrogels (HGs) formulations were developed as potential mucoadhesive systems for risperidone (RISP) oral transmucosal delivery. The suitability of the prepared semi-solid formulations for application on oral mucosa was assessed by means of rheological and textural analysis, during 30 days. Plastic flows with thixotropy and high adhesiveness were obtained for all the tested systems, which predict their success for the oral transmucosal application proposed. The SLN remained within the colloidal range after HGs preparation. However, after 30 days of storage, a particle size increase was detected in one type of the HGs formulations. In vitro drug release studies revealed a more pronounced RISP release after SLN hydrogel entrapment, when compared to the dispersions alone. In addition, a pH-dependent release was observed as well. The predicted in vivo RISP release mechanism was Fickian diffusion alone or combined with erosion.
Constrained Vs. Unconstrained Intensive Language Therapy in Two Individuals with Chronic, Moderate-to-Severe Aphasia and Apraxia of Speech: Behavioral and FMRI Outcomes
American Journal of Speech-language Pathology / American Speech-Language-Hearing Association. Jan, 2012 | Pubmed ID: 22294409
PURPOSE: This Phase I study investigated behavioral and fMRI outcomes of two intensive treatment programs to improve naming in two participants with chronic moderate-to-severe aphasia with co-morbid apraxia of speech (AOS). Constraint-induced aphasia therapy (CIAT) has demonstrated positive outcomes in some chronically aphasic individuals. Whether constraint to the speech modality or treatment intensity is responsible for such gains is still under investigation. Moreover, it remains to be seen whether CIAT is effective in persons with persistent severe nonfluent speech, and/or AOS. METHOD: A single-subject multiple baseline approach was utilized. Participants were treated simultaneously, first with PACE, and then CIAT. Pre/post-treatment testing included an overt naming fMRI protocol. Treatment effect sizes were calculated for changes in probe accuracy from baseline to post-treatment phases, and maintenance where available. RESULTS: Both participants made more and faster gains in naming following CIAT. Treatment-induced changes in BOLD activation suggested that better naming was correlated with recruitment of perilesional tissue. CONCLUSIONS: Participants accurately produced more target words post-CIAT than post-PACE. Behavioral and fMRI results support the notion that the intense and repetitive nature of obligatory speech production in CIAT has a positive effect on word retrieval, even in chronic moderate-to-severe aphasia with co-morbid AOS.
Sleep. 2012 | Pubmed ID: 22294812
One task that has been used to assess memory effects of prior total sleep deprivation (TSD) is the immediate free recall of word lists; however, results have been mixed. A possible explanation for this is task impurity, since recall of words from different serial positions reflects use of distinct types of memory (last words: short-term memory; first and intermediate words: episodic memory). Here we studied the effects of 2 nights of TSD on immediate free recall of semantically unrelated word lists considering the serial position curve.
PloS One. 2012 | Pubmed ID: 22295089
Many cases of Cutaneous Larva Migrans (CLM) have been observed among devotees, during and immediately after the annual festival at the Nallur Hindu temple in Jaffna.
Resveratrol-derived Stilbenoids and Biological Activity Evaluation of Seed Extracts of Cenchrus Echinatus L
Natural Product Research. Jan, 2012 | Pubmed ID: 22292784
A phytochemical study of the ethyl acetate fractions from the partition of seeds and roots methanol extracts of Cenchrus echinatus L. led to the isolation of three resveratrol-derived stilbenoids: pallidol (1), carasiphenol C (2) and nepalensinol B (3). The results of a topic anti-inflammatory evaluation, DPPH assay and antiproliferative activity against adenocarcinoma cells (Caco 2) are described.
Natural Product Research. Jan, 2012 | Pubmed ID: 22292909
Spiranthera odoratissima A. St.-Hil., 'manacá', is a medicinal species used in Brazil, especially in central region, for the treatment of several diseases such as pain and inflammation. In this study, the methanol/aqueous phase of the ethanol extract of the leaves of 'manacá' (MAP), at the doses of 50, 150 and 500 mg/kg was used to evaluate the anti-inflammatory and/or antinociceptive effects and the possible anti-inflammatory mechanism. The antinociceptive and anti-inflammatory activities of MAP were assessed using formalin test, carrageenan-induced paw oedema. The myeloperoxidase activity, capillary permeability, leukocyte migration and tumour necrosis factor alpha (TNF-α) levels were evaluated in pleural exudate. The MAP reduced the licking time only in the later phase of formalin test, and showed anti-inflammatory activity by reducing the paw oedema, migration cell, myeloperoxidase activity, capillary permeability and TNF-α levels. In conclusion, we confirmed the inflammatory activity of MAP and affirm that this effect involves the reduction of TNF-α level.
Adverse Psychosocial Working Conditions and Poor Quality of Life Among Financial Service Employees in Brazil
Journal of Occupational Health. Jan, 2012 | Pubmed ID: 22293244
Objectives: Workers in the financial services sector are exposed to great stress at work. This study investigates whether exposure to adverse psychosocial work conditions is independently associated with poor health-related physical and mental quality of life among financial services workers. Methods: We studied a nationwide representative sample of 2,054 workers of a large Brazilian state bank in 2008. Adverse psychosocial work conditions were investigated by the Effort-Reward Imbalance (ERI) scale and the Job Content Questionnaire (JCQ). Health-related quality of life (HRQL) was assessed using the Medical Outcomes Study Short-Form General Health Survey (SF-12). Poor mental and physical HRQL was defined by the lowest quartiles of the SF-12 final score distributions. Associations were investigated using multiple logistic regression analysis. Results: In the multivariate analysis, exposures to low control and lack of social support at work (JCQ) were associated with poor HRQL in the physical domain. Increasing effort-reward imbalance and overcommitment (ERI), on the other hand, were associated with poor HRQL in the mental domain, with a significant statistical trend. Overcommitment was also associated with poor physical HRQL. Conclusion: The results suggest that exposure to adverse psychosocial work conditions has a negative impact on both domains of HRQL among financial service workers. They also indicate that ERI and DC models capture different aspects of job strain.
Chronic Exercise Partially Restores the Transmural Heterogeneity of Action Potential Duration in Left Ventricular Myocytes of Spontaneous Hypertensive Rats
Clinical and Experimental Pharmacology & Physiology. Feb, 2012 | Pubmed ID: 22288490
Hypertension leads to electrophysiological changes in the heart. Chronic exercise induced by a treadmill-running programme (TRP) is considered a potential non-pharmacological treatment for hypertension and may have implications in heart remodelling. However, it is not known whether the TRP is able to improve the electrophysiological properties of the heart in spontaneously hypertensive rats (SHR). In the present study, we investigated whether TRP affects the electrical properties of left ventricular (LV) myocytes isolated from different layers of the LV wall of SHR. Male SHR were divided into exercised (chronic treadmill running for 8 weeks; CEX-SHR) and sedentary (SED-SHR) groups. Age-matched normotensive Wistar male rats served as controls. Action potentials (AP) and transient outward potassium current (I(to) ) were recorded in subepicardial (EPI) and subendocardial (ENDO) LV myocytes. In normotensive controls, AP duration (APD) was longer in ENDO cells than in EPI cells. This sort of transmural heterogeneity in the LV was not observed in sedentary SHR and was partially restored in SHR subject to chronic exercise. This partial recovery was associated with an increase in I(to) density in EPI cells but not in ENDO cells. The electrophysiological changes observed in the CEX-SHR group were not accompanied by either amelioration of systolic blood pressure or a reduction in heart hypertrophy. These findings imply that a TRP is able to improve the electrophysiological parameters of isolated cardiac myocytes in SHR. This sort of adaptation contributes to the overall improvement of heart physiology in this model.
Theriogenology. Jan, 2012 | Pubmed ID: 22289215
The objective was to assess the effects of the antioxidants resveratrol and quercetin on frozen-thawed ram sperm. Semen samples (which exceeded minimum standards) from four mature crossbreed Santa Inês rams were pooled and aliquots of each pool were diluted in Tris-egg yolk-glycerol, with the addition of 0, 5, 10, 15, and 20 μg/mL of resveratrol and quercetin in Experiment 1 and Experiment 2, respectively. In Experiment 1, the proportion of sperm with a high mitochondrial membrane potential was greater (P < 0.02) in the control group than in resveratrol 20 μg/mL group. In Experiment 2, the proportion of sperm with high mitochondrial membrane potential was greater in the control group (P < 0.0001) than in the other experimental groups, and greater in the quercetin 5 μg/mL group (P < 0.05) than in the other quercetin-treated groups. Thus, addition of 5 to 20 μg/mL of either resveratrol or quercetin to the Tris-egg yolk-glycerol extender reduced sperm mitochondrial membrane potential.
Therapeutic Ultrasound As a Potential Male Contraceptive: Power, Frequency and Temperature Required to Deplete Rat Testes of Meiotic Cells and Epididymides of Sperm Determined Using a Commercially Available System
Reproductive Biology and Endocrinology : RB&E. Jan, 2012 | Pubmed ID: 22289508
ABSTRACT: BACKGROUND: Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive. METHODS: Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment. RESULTS: We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline) was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days. CONCLUSIONS: The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the result of repeated use, to verify that the contraceptive effect is reversible and to demonstrate that there are no detrimental, long-term effects from using ultrasound as a method of male contraception.
Phytochemistry. Jan, 2012 | Pubmed ID: 22289621
The dichloromethane extract from taproots of Hortia oreadica afforded six limonoids, these are 9,11-dehydro-12α-acetoxyhortiolide A, hortiolide C, 11α-acetoxy-15-deoxy-6-hydroxyhortiolide C, hortiolide D, hortiolide E, 12β-hydroxyhortiolide E, in addition to the known limonoid, guyanin. The dichloromethane extract from stems of H. oreadica also afforded two limonoids 9,11-dehydro-12α-hydroxyhortiolide A and 6-hydroxyhortiolide C. As a result of this study and literature data, Hortia has been shown to produce highly specialized limonoids that are similar to those from the Flindersia (Flindersioideae). The taxonomy of Hortia has been debatable, with most authors placing it in the Toddalioideae. Considering the complexity of the isolated limonoids, Hortia does not show any close affinity to the genera of Toddalioideae. That is, the limonoids appear to be of little value in resolving the taxonomic situation of Hortia.
Cyclosporine A Enables Vincristine-induced Apoptosis During Reversal of Multidrug Resistance Phenotype in Chronic Myeloid Leukemia Cells
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Jan, 2012 | Pubmed ID: 22290425
Multidrug resistance (MDR) is considered a multifactorial phenotype which prevents a successful clinical cancer treatment. This phenomenon is mainly associated with mechanisms that include drug extrusion by P-glycoprotein (Pgp) overexpression and resistance to apoptosis derived by members of the inhibitor of apoptosis proteins (IAPs), such as XIAP. Studies have proposed the use of compounds that are able to inhibit or modulate Pgp function, with no changes in the physiological expression of this protein. Based on that, the present study aimed to evaluate the reversal of MDR phenotype through modulation of Pgp efflux pump activity in leukemia multidrug-resistant cells, using a low dose of cyclosporine A (CsA). We showed that modulation of Pgp activity by using CsA did not induce cytotoxic effects in leukemia cells, independently of Pgp expression. However, during the modulation condition, we could observe that vincristine-induced apoptosis was significant in resistant cells, which was also coupled with decreasing expression of the inhibitor of apoptosis protein XIAP. In summary, our data suggest that CsA is able to reversing MDR phenotype in vitro, inducing sensibility in multidrug-resistant cells with no alterations in Pgp expression. These findings contribute to our knowledge for the circumvention of MDR in cancer cells and could be helpful for new treatment approaches.
Cephalalgia : an International Journal of Headache. Jan, 2012 | Pubmed ID: 22290555
Background: It is not known whether smoking by mothers during pregnancy is associated with headache in their offspring.Methods: Two prospective cohorts of 869 children aged 10-11 years from Ribeirão Preto (RP) and 805 children aged 7-9 years from São Luís (SL) were studied. Data on maternal smoking were collected at birth. Primary headache was defined as a reporting of 2 episodes of headache in the past 2 weeks, without any associated organic symptoms.Results: Prevalence of headache was 28.1% in RP and 13.1% in SL as reported by the mothers and 17.5% in RP and 29.4% in SL as reported by the children. Agreement between mothers' report and children's self-report of primary headache in the child was poor. After adjustment, children whose mothers smoked 10 cigarettes per day during pregnancy presented higher prevalence of primary headache than their counterparts in both cohorts, as reported by the mother and in RP as reported by the children.Conclusions: Maternal smoking during pregnancy was associated with headache in 7- to 11-year-olds. With one exception, the consistency of the results, despite poor agreement between maternal and children reports of headache, indicates that maternal smoking during pregnancy may contribute to headaches in their children.
Journal of Child Neurology. Jan, 2012 | Pubmed ID: 22290861
We report a female patient with situs inversus, dextrocardia, a complex heart malformation, hydrocephalus due to aqueductal stenosis, and abnormal ultrastructure of the respiratory epithelium cilia. Several animal models of this disorder implicate abnormal ciliary function in the genesis of hydrocephalus, and 11 patients were previously reported with hydrocephalus and the syndrome of primary ciliary dyskinesia. Primary ciliary dyskinesia-associated aqueductal stenosis should be considered as a possible cause for fetal or neonatal hydrocephalus if heterotaxy, heart malformations, and/or a probable genetic etiology are present.
Deciphering the Magainin-resistance Process of Escherichia Coli Strains in Light of the Cytosolic Proteome
Antimicrobial Agents and Chemotherapy. Jan, 2012 | Pubmed ID: 22290970
Antimicrobial peptides (AMPs) are effective antibiotic agents commonly found in plants, animals and microorganisms being suggested as the future of antimicrobial chemotherapies. It is vital to understand the molecular details that define the mechanism of action of and resistance to AMPs for a rational planning of the next antibiotic generation and also to shed some light on the complex AMP mechanism of action. Here, the antibiotic resistance of Escherichia coli ATCC 8739 to magainin I was evaluated in the cytosolic sub-proteome. Magainin-resistant strains were selected after 10 subsequent spreads at sub-inhibitory concentrations of magainin I (37.5 mg.L(-1)) and their cytosolic proteomes were further compared with magainin-susceptible strains through two-dimensional electrophoresis analysis. As a result, 41 differentially expressed proteins were detected by in silico analysis and further identified by MS/MS de novo sequencing. Functional categorization indicated an intense metabolic response mainly in energy and nitrogen uptake, stress response, amino acid conversion and cell wall thickness. Indeed, data here reported show that resistance to cationic antimicrobial peptides possesses a higher molecular complexity than previously supposed, resulting in a cell commitment to several metabolic pathways.
Reply to "do Children Exposed to Human Immunodeficiency Virus but Not Infected Actually Have a More Robust Response to Hepatitis B Vaccination Than Their Nonexposed Peers?"
Clinical and Vaccine Immunology : CVI. Feb, 2012 | Pubmed ID: 22290992
ISP: An Optimal Out-Of-Core Image-Set Processing Streaming Architecture for Parallel Heterogeneous Systems
IEEE Transactions on Visualization and Computer Graphics. Jan, 2012 | Pubmed ID: 22291156
Image population analysis is the class of statistical methods that plays a central role in understanding the development, evolution and disease of a population. However, these techniques often require excessive computational power and memory that are compounded with a large number of volumetric inputs. Restricted access to supercomputing power limits its influence in general research and practical applications. In this paper we introduce ISP, an Image-Set Processing streaming framework that harnesses the processing power of commodity heterogeneous CPU/GPU systems and attempts to solve this computational problem. In ISP we introduce specially-designed streaming algorithms and data structures that provide an optimal solution for out-of-core multi-image processing problems both in terms of memory usage and computational efficiency. ISP makes use of the asynchronous execution mechanism supported by parallel heterogeneous systems to efficiently hide the inherent latency of the processing pipeline of out-of-core approaches. Consequently, with computationally intensive problems, the ISP out-of-core solution can achieve the same performance as the in-core solution. We demonstrate the efficiency of the ISP framework on synthetic and real datasets.
Leptospiral Immunoglobulin-like Proteins Interact With Human Complement Regulators Factor H, FHL-1, FHR-1, and C4BP
The Journal of Infectious Diseases. Jan, 2012 | Pubmed ID: 22291192
Leptospira, the causative agent of leptospirosis, interacts with several host molecules, including extracellular matrix components, coagulation cascade proteins, and human complement regulators. Here we demonstrate that acquisition of factor H (FH) on the Leptospira surface is crucial for bacterial survival in the serum and that these spirochetes, besides interacting with FH, FH related-1, and C4b binding protein (C4BP), also acquire FH like-1 from human serum. We also demonstrate that binding to these complement regulators is mediated by leptospiral immunoglobulin-like (Lig) proteins, previously shown to interact with fibronectin, laminin, collagen, elastin, tropoelastin, and fibrinogen. Factor H binds to Lig proteins via short consensus repeat domains 5 and 20. Competition assays suggest that FH and C4BP have distinct binding sites on Lig proteins. Moreover, FH and C4BP bound to immobilized Ligs display cofactor activity, mediating C3b and C4b degradation by factor I. In conclusion, Lig proteins are multifunctional molecules, contributing to leptospiral adhesion and immune evasion.
In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - Against Trypanosoma Cruzi Infection
PloS One. 2012 | Pubmed ID: 22291940
Chagas disease is caused by infection with the intracellular protozoan parasite Trypanosoma cruzi. At present, nifurtimox and benznidazole, both compounds developed empirically over four decades ago, represent the chemotherapeutic arsenal for treating this highly neglected disease. However, both drugs present variable efficacy depending on the geographical area and the occurrence of natural resistance, and are poorly effective against the later chronic stage. As a part of a search for new therapeutic opportunities to treat chagasic patients, pre-clinical studies were performed to characterize the activity of a novel arylimidamide (AIA - DB1831 (hydrochloride salt) and DB1965 (mesylate salt)) against T.cruzi. These AIAs displayed a high trypanocidal effect in vitro against both relevant forms in mammalian hosts, exhibiting a high selectivity index and a very high efficacy (IC(50) value/48 h of 5-40 nM) against intracellular parasites. DB1965 shows high activity in vivo in acute experimental models (mouse) of T.cruzi, showing a similar effect to benznidazole (Bz) when compared under a scheme of 10 daily consecutive doses with 12.5 mg/kg. Although no parasitological cure was observed after treating with 20 daily consecutive doses, a combined dosage of DB1965 (5 mg/kg) with Bz (50 mg/kg) resulted in parasitaemia clearance and 100% animal survival. In summary, our present data confirmed that aryimidamides represent promising new chemical entities against T.cruzi in therapeutic schemes using the AIA alone or in combination with other drugs, like benznidazole.
PloS One. 2012 | Pubmed ID: 22292008
Genome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius.
PLoS Neglected Tropical Diseases. Jan, 2012 | Pubmed ID: 22292094
Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.
Osteochondral Transplantation Using Autografts from the Upper Tibio-fibular Joint for the Treatment of Knee Cartilage Lesions
Knee Surgery, Sports Traumatology, Arthroscopy : Official Journal of the ESSKA. Jan, 2012 | Pubmed ID: 22286745
PURPOSE: Treatment of large cartilage lesions of the knee in weight-bearing areas is still a controversy and challenging topic. Autologous osteochondral mosaicplasty has proven to be a valid option for treatment but donor site morbidity with most frequently used autografts remains a source of concern. This study aims to assess clinical results and safety profile of autologous osteochondral graft from the upper tibio-fibular joint applied to reconstruct symptomatic osteochondral lesions of the knee. METHODS: Thirty-one patients (22 men and 9 women) with grade 4 cartilage lesions in the knee were operated by mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint, between 1998 and 2006. Clinical assessment included visual analog scale (VAS) for pain and Lysholm score. All patients were evaluated by MRI pre- and post-operatively regarding joint congruency as good, fair (inferior to 1 mm incongruence), and poor (incongruence higher than 1 mm registered in any frame). Donor zone status was evaluated according to specific protocol considering upper tibio-fibular joint instability, pain, neurological complications, lateral collateral ligament insufficiency, or ankle complaints. RESULTS: Mean age at surgery was 30.1 years (SD 12.2). In respect to lesion sites, 22 were located in weight-bearing area of medial femoral condyle, 7 in lateral femoral condyle, 1 in trochlea, and 1 in patella. Mean follow-up was 110.1 months (SD 23.2). Mean area of lesion was 3.3 cm(2) (SD 1.7), and a variable number of cylinders were used, mean 2.5 (SD 1.3). Mean VAS score improved from 47.1 (SD 10.1) to 20.0 (SD 11.5); p = 0.00. Similarly, mean Lysholm score increased from 45.7 (SD 4.5) to 85.3 (SD 7.0); p = 0.00. The level of patient satisfaction was evaluated, and 28 patients declared to be satisfied/very satisfied and would do surgery again, while 3 declared as unsatisfied with the procedure and would not submit to surgery again. These three patients had lower clinical scores and kept complaints related to the original problem but unrelated to donor zone. MRI score significantly improved at 18-24 months comparing with pre-operative (p = 0.004). No radiographic or clinical complications related to donor zone with implication in activity were registered. CONCLUSIONS: This work corroborates that mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint is effective to treat osteochondral defects in the knee joint. No relevant complications related to donor zone were registered. LEVEL OF EVIDENCE: Case series, Level IV.
Alkylation-induced Genotoxicity As a Predictor of DNA Repair Deficiency Following Experimental Oral Carcinogenesis
Journal of Molecular Histology. Jan, 2012 | Pubmed ID: 22287026
The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis by means of single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 μL each to study basal DNA damage and DNA damage due to genotoxin sensitivity. The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate. Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks post-treatment. Peripheral blood cells did show statistically significant differences (P < 0.05) after 20 weeks-group (squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.
Texture Analysis of High Resolution MRI Allows Discrimination Between Febrile and Afebrile Initial Precipitating Injury in Mesial Temporal Sclerosis
Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jan, 2012 | Pubmed ID: 22287318
A computational pipeline combining texture analysis and pattern classification algorithms was developed for investigating associations between high-resolution MRI features and histological data. This methodology was tested in the study of dentate gyrus images of sclerotic hippocampi resected from refractory epilepsy patients. Images were acquired using a simple surface coil in a 3.0T MRI scanner. All specimens were subsequently submitted to histological semiquantitative evaluation. The computational pipeline was applied for classifying pixels according to: a) dentate gyrus histological parameters and b) patients' febrile or afebrile initial precipitating insult history. The pipeline results for febrile and afebrile patients achieved 70% classification accuracy, with 78% sensitivity and 80% specificity [area under the reader observer characteristics (ROC) curve: 0.89]. The analysis of the histological data alone was not sufficient to achieve significant power to separate febrile and afebrile groups. Interesting enough, the results from our approach did not show significant correlation with histological parameters (which per se were not enough to classify patient groups). These results showed the potential of adding computational texture analysis together with classification methods for detecting subtle MRI signal differences, a method sufficient to provide good clinical classification. A wide range of applications of this pipeline can also be used in other areas of medical imaging. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Arquivos De Neuro-psiquiatria. Jan, 2012 | Pubmed ID: 22286405
Revista Brasileira De Reumatologia. Feb, 2012 | Pubmed ID: 22286644
OBJECTIVES: To evaluate the alveolar bone density (ABD) in the upper first molars of patients with juvenile idiopathic arthritis (JIA) and to compare their ABD with that of healthy controls. Secondary objectives included the evaluation of the influence of medication and rheumatic disease activity on ABD, in addition to the correlation between ABD and periodontal and rheumatologic clinical parameters. PATIENTS AND METHODS: This study assessed 16 patients with JIA (six boys and 10 girls; mean age, 16.2 ± 2 years) and 11 controls (six boys and five girls; mean age, 16.4 ± 2.1 years). Probing depth (PD), visible plaque index, gingival bleeding on probing (GBP), and the clinical insertion level (CIL) were recorded. Bite-wing radiographs were obtained and ABD was measured in the upper molars by use of the Kodak RVG 6100 Digital Radiography System. RESULTS: ABD, the percentage of sites with PD > 4 mm, and GBP were significantly lower in patients with JIA than in controls (P = 0.001; P = 0.019; P = 0.011, respectively). ABD was influenced by neither medication nor JIA activity, and showed no correlation with periodontal and rheumatologic clinical parameters. CONCLUSION: ABD was lower in patients with JIA and seemed to be influenced by neither medication nor rheumatic disease activity. In addition, no correlation was observed between ABD and periodontal and rheumatologic clinical parameters.
Revista Brasileira De Reumatologia. Feb, 2012 | Pubmed ID: 22286650
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, and its excess can lead to severe consequences. Those effects are known to be antagonized by TNF-alpha inhibitors. Etanercept is a fusion protein that inhibits TNF-alpha action. As TNF-alpha regulation is related to cellular differentiation of various cellular types involved in immune response through expression of several other cytokines, it is possible that the use of its inhibitors may cause cytopenia. We report two cases of bicytopenia induced by etanercept. Both cases recovered after drug withdrawal. We discuss the need of introduction of routine laboratorial tests in patients using anti-TNF therapy, in order to identify possible hematological changes.
General Dentistry. Jan, 2012 | Pubmed ID: 22313987
This article presents a prototype of an intraoral device that facilitates preparation of parallel guide planes with accuracy and minimal occlusal divergence. The design of this device facilitates transfer of the desired path of insertion from the diagnostic cast to the mouth quickly and efficiently.
Palynological Origin, Phenolic Content, and Antioxidant Properties of Honeybee-collected Pollen from Bahia, Brazil
Molecules (Basel, Switzerland). 2012 | Pubmed ID: 22314384
The aim of this study was to determine the palynological origin, phenolic and flavonoid content, and antioxidant properties of twenty-five samples of bee pollen harvested during a nine-month period (February-November) from the Canavieiras municipality (northeastern Brazil). Of the 25 samples analyzed, only two (February 01 and 02) were heterofloral. The predominant pollens in the samples analyzed during that month were: Cecropia, Eucalyptus, Elaeis, Mimosa pudica, Eupatorium, and Scoparia. Ethyl acetate fractions were analyzed by HPLC-DAD. The flavonoids isoquercetin, myricetin, tricetin, quercetin, luteolin, selagin, kaempferol, and isorhamnetin were detected. The flavonoid present in all 22 samples was isolated and identified as isorhamnetin 3-O-b-neohesperidoside. The total phenolic contents determined using the Folin-Ciocalteu reagent ranged from 41.5 to 213.2 mg GAE/g. Antioxidant activities based on the 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiozoline-6-sulfonic acid (ABTS), and Fe2+ ion chelating activity assays were observed for all extracts, and correlated with the total phenolic content.
Microspatial Distributional Patterns of Vectors of Cutaneous Leishmaniasis in Pernambuco, Northeastern Brazil
Journal of Tropical Medicine. 2012 | Pubmed ID: 22315619
The purpose of this study is to analyze the spatial distribution and population trends through time of Lutzomyia species in a long-term focus of cutaneous leishmaniasis transmission in an Atlantic Forest area, northeastern Brazil. Sand fly populations of different ecological niches were monitored spatiotemporally in 2009. To summarize vegetation characteristics and phenology, we calculated the Normalized Difference Vegetation Index from Landsat images. Using niche modeling approaches, we assessed suites of environmental factors to identify areas of transmission risk. Although 12 species were detected, L. whitmani was the most abundant and broadly distributed across the area, particularly in peridomiciliary locations, and associated negatively with denser vegetation areas. On the other hand, L. complexa, L. sordelli, and L. tupynambai were found almost exclusively in forested areas (P < 0.05), and associated positively with denser vegetation. Lutzomyia species' occurrences are related to specific environmental combinations (with contrast among species) in the region.
Co-occurrence of Aflatoxins B(1), B(2), G(1) and G(2), Ochratoxin A, Zearalenone, Deoxynivalenol, and Citreoviridin in Rice in Brazil
Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. Jan, 2012 | Pubmed ID: 22316345
A total of 230 samples of processed rice and its sub-products or derived products were analysed to establish the co-occurrence of several mycotoxins. Samples were analysed in the period 2007-2009 due to the outbreak of beriberi associated with the consumption of rice stored in inappropriate conditions in Brazil. According to data from the Ministry of Health, 323 cases of disease were registered in 2006, of which at least 47 cases resulted in death. The occurrence of total aflatoxin (AFT) (aflatoxin B(1) + B(2) + G(1) + G(2)), ochratoxin A (OTA), zearalenone (ZON), deoxynivalenol (DON), and citreoviridin (CTV) was 58.7%, 40.0%, 45.2%, 8.3% and 22.5%, respectively. From 166 rice samples analysed, 55% had levels <0.11 µg kg(-1) for AFT. For OTA and ZON, of 165 rice samples analysed, 28% and 29% were contaminated with levels from 0.20 to 0.24 µg kg(-1) and from 3.6 to 290.0 µg kg(-1), respectively. One sample (0.6%) was contaminated with 4872.0 µg kg(-1) of ZON. A total of 91% of rice samples (n = 165) did not contain detectable DON (<30.00 µg kg(-1)), although the highest level of contamination was found to be 244 µg kg(-1). From the total of 65 samples analysed, 94% had no detectable CTV (<0.9 µg kg(-1)), with a range from 0.9 to 31.1 µg kg(-1) in 6% of the samples. The highest levels of contamination were found in rice sub-products or derived products from the husk and rice bran. Co-occurrence was observed for AFT and ZON in 17.0%, AFT and OTA in 24.2%, AFT and CTV in 6.2%, OTA and CTV in 4.6%, and ZON and CTV in 3.1%. These fractions were also the major contributors for the co-occurrence. The results found show the necessity of monitoring rice production.
Fertility and Sterility. Feb, 2012 | Pubmed ID: 22317821
OBJECTIVE: To characterize the deletion patterns and its breakpoints in oligozoospermic patients presenting AZFb and AZFc microdeletions and to understand the recombination mechanisms underlying these microdeletions. DESIGN: Case report. SETTING: Genetics Department of Faculty of Medicine of Porto, Porto, Portugal. PATIENT(S): Two men with severe oligozoospermia and two men with nonobstructive azoospermia identified as having different AZFb+c deletion patterns via Y chromosome microdeletion analysis. INTERVENTION(S): Definition of microdeletions and the fine characterization of the respective breakpoints by sequence-tagged sites (STS) polymerase chain reaction (PCR) and single-nucleotide variant (SNV) PCR. MAIN OUTCOME MEASURE(S): Study of the fine structure of the Y-chromosome and discussion of the putative mechanisms involved in each microdeletion pattern. RESULT(S): From the four patients studied, three deletion patterns were identified: IR4/distal-P2 (25%; 1 of 4), P5/proximal-P1 (50%; 2 of 4), and P5/distal-P1 (25%; 1 of 4). Although severe oligozoospermia is normally associated with AZFc, a complete AZFb deletion was found in one case. CONCLUSION(S): Analysis of these patients has revealed a new putative region that may be involved in spermatogenesis conservation.
Evaluation of Participant Satisfaction with Community Therapy: A Mental Health Strategy in Primary Care
The Psychiatric Quarterly. Feb, 2012 | Pubmed ID: 22318711
Actions aimed at health promotion and disease prevention must prioritize the entry point to the health system. In this sense, it is proposed that Community Therapy (CT) be inserted as a mental health care tool in Primary Care. The purpose of this study is to assess user satisfaction with CT in Primary Care. It is assessment, cross-sectional study with a representative sample of users of CT services in Primary Care in the municipality of João Pessoa, Paraiba, Brazil. Of the 198 interviewees, 165 (83.3%) of the sample reported that they were always respected, evidenced by aspects of respect and dignity; 109 (55.1%) individuals stated they were listened to, revealing internal consistency of 0.7187, and in turn, exhibiting the true validity of the user satisfaction construct with respect to CT. Thus, users displayed positive satisfaction, reflected by respect, dignity, receptiveness, resolution, listening and comprehension received at CT, where empathy is exhibited and mental suffering is relieved. Moreover, CT is an important mental health tool in primary care.
Can Phlorotannins Purified Extracts Constitute a Novel Pharmacological Alternative for Microbial Infections with Associated Inflammatory Conditions?
PloS One. 2012 | Pubmed ID: 22319609
Bacterial and fungal infections and the emerging multidrug resistance are driving interest in fighting these microorganisms with natural products, which have generally been considered complementary to pharmacological therapies. Phlorotannins are polyphenols restricted to brown seaweeds, recognized for their biological capacity. This study represents the first research on the antibacterial, antifungal, anti-inflammatory and antioxidant activity of phlorotannins purified extracts, which were obtained from ten dominant brown seaweeds of the occidental Portuguese coast.Phlorotannins content was determined by the specific dimethoxybenzaldehyde (DMBA) method and a yield between 75 and 969 mg/Kg phloroglucinol units (dry matter) was obtained. Fucus spiralis ranked first, followed by three Cystoseira species. The anti-inflammatory potential of the purified extracts was assessed via inhibitory effect on nitric oxide (NO) production by lipopolysaccharide-stimulated RAW 264.7 macrophage cells, Cystoseira tamariscifolia being the one showing promising activity for the treatment of inflammation. NO scavenging ability was also addressed in cell free systems, F. spiralis being the species with highest capacity. The antimicrobial potential of the extracts was checked against five Gram-positive and four Gram-negative bacteria and three fungi strains, that commonly colonize skin and mucosa and are responsible for food contamination. The different extracts were more effective against Gram-positive bacteria, Staphylococcus epidermidis being the most susceptible species. Concerning antifungal activity, Trichophyton rubrum was the most sensitive species.Although the molecular mechanisms underlying these properties remain poorly understood, the results obtained turn phlorotannins purified extracts a novel and potent pharmacological alternative for the treatment of a wide range of microbial infections, which usually also present an inflammatory component. In addition to the biological properties demonstrated herein, phlorotannins extracts may also be preferred, in order to avoid side effects and allergic reactions commonly associated with synthetic drugs.
Endothelin-1 Induces Neutrophil Recruitment in Adaptive Inflammation Via TNFα and CXCL1/CXCR2 in Mice
Canadian Journal of Physiology and Pharmacology. Feb, 2012 | Pubmed ID: 22320712
Endothelin mediates neutrophil recruitment during innate inflammation. Herein we address whether endothelin-1 (ET-1) is involved in neutrophil recruitment in adaptive inflammation in mice, and its mechanisms. Pharmacological treatments were used to determine the role of endothelin in neutrophil recruitment to the peritoneal cavity of mice challenged with antigen (ovalbumin) or ET-1. Levels of ET-1, tumour necrosis factor α (TNFα), and CXC chemokine ligand 1 (CXCL1) were determined by enzyme-linked immunosorbent assay. Neutrophil migration and flow cytometry analyses were performed 4 h after the intraperitoneal stimulus. ET-1 induced dose-dependent neutrophil recruitment to the peritoneal cavity. Treatment with the non-selective ET(A)/ET(B) receptor antagonist bosentan, and selective ET(A) or ET(B) receptor antagonists BQ-123 or BQ-788, respectively, inhibited ET-1- and ovalbumin-induced neutrophil migration to the peritoneal cavity. In agreement with the above, the antigen challenge significantly increased levels of ET-1 in peritoneal exudates. The ET-1- and ovalbumin-induced neutrophil recruitment were reduced in TNFR1 deficient mice, and by treatments targeting CXCL1 or CXC chemokine receptor 2 (CXCR2); further, treatment with bosentan, BQ-123, or BQ-788 inhibited ET-1- and antigen-induced production of TNFα and CXCL1. Furthermore, ET-1 and ovalbumin challenge induced an increase in the number of cells expressing the Gr1(+) markers in the granulocyte gate, CD11c(+) markers in the monocyte gate, and CD4(+) and CD45(+) (B220) markers in the lymphocyte gate in an ET(A)- and ET(B)-dependent manner, as determined by flow cytometry analysis, suggesting that ET-1 might be involved in the recruitment of neutrophils and other cells in adaptive inflammation. Therefore, the present study demonstrates that ET-1 is an important mediator for neutrophil recruitment in adaptive inflammation via TNFα and CXCL1/CXCR2-dependent mechanism.
Comparisons of Treatment Optimization Directly Incorporating Systematic Patient Setup Uncertainty with a Margin-based Approach
Medical Physics. Feb, 2012 | Pubmed ID: 22320820
Purpose: To develop a probabilistic treatment planning (PTP) method which is robust to systematic patient setup errors and to compare PTP plans with plans generated using a planning target volume (PTV) margin optimized to give the same target coverage probability as the PTP plan.Methods: Plans adhering to the RTOG-0126 protocol are developed for 28 prostate patients using PTP and margin-based planning. For PTP, an objective function that simultaneously considers multiple possible patient positions is developed. PTP plans are optimized using clinical target volume (CTV) structures and organ at risk (OAR) structures. The desired CTV coverage probability is 95%. Plans that cannot achieve a 95% CTV coverage probability are re-optimized with a desired CTV coverage probability reduced by 5% until the desired CTV coverage probability is achieved. Margin-based plans are created which achieve the same CTV coverage probability as the PTP plans by iterative adjustment of the CTV-to-PTV margin. Postoptimization, probabilistic dose-volume coverage metrics are used to compare the plans.Results: For equivalent target coverage probability, PTP plans significantly reduce coverage probability for rectum objectives (-17% for D(35) < 65 Gy, p = 0.0010; -23% for D(25) < 70 Gy, p < 0.0001; and -27% for D(15) < 75 Gy, p < 0.0001). Physician assessment indicates PTP plans are entirely preferred 71% of the time while margin-based plans are entirely preferred 7% of the time.Conclusions: For plans having the same target coverage probability, PTP has potential to reduce rectal doses while maintaining CTV coverage probability. In blind comparisons, physicians prefer PTP plans over optimized margin plans. (Work supported by NIH P01CA116602 and T32CA113277.).
Health Research Policy and Systems / BioMed Central. Feb, 2012 | Pubmed ID: 22321566
ABSTRACT: BACKGROUND: Little is known about how health research systems (HRS) in low-income countries emerge and evolve over time, and how this process relates to their performance. Understanding how HRSs emerge is important for the development of well functioning National Health Research Systems (NHRS). The aim of this study was to assess how the HRS in Guinea Bissau has emerged and evolved over time and how the present system functions. METHODS: We used a qualitative case-study methodology to explore the emergence and current performance of the HRS, using the NHRS framework. We reviewed documents and carried out 39 in-depth interviews, ranging from health research to policy and practice stakeholders. Using an iterative approach, we undertook a thematic analysis of the data. FINDINGS: The research practices in Guinea Bissau led to the emergence of a HRS with both local and international links and strong dependencies on international partners and donors. The post-colonial, volatile and resource-dependent context, changes in donor policies, training of local researchers and nature of the research findings influenced how the HRS evolved. Research priorities have mostly been set by 'expatriate' researchers and focused on understanding and reducing child mortality. Research funding is almost exclusively provided by foreign donors and international agencies. The training of Guinean researchers started in the mid-nineties and has since reinforced the links with the health system, broadened the research agenda and enhanced local use of research. While some studies have made an important contribution to global health, the use of research within Guinea Bissau has been constrained by the weak and donor dependent health system, volatile government, top-down policies of international agencies, and the controversial nature of research findings. CONCLUSIONS: In Guinea Bissau a de facto 'system' of research has emerged through research practices and co-evolving national and international research and development dynamics. If the aim of research is to contribute to local decision making, it is essential to modulate the emerged system by setting national research priorities, aligning funding, building national research capacity and linking research to decision making processes. Donors and international agencies can contribute to this process by coordinating their efforts and aligning to national priorities.
International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. Feb, 2012 | Pubmed ID: 22321725
OBJECTIVES: To explore clinical and socioeconomic factors related to congenital syphilis in Posadas, Argentina. METHODS: Data were collected from 102 mothers who had given birth to an infant with congenital syphilis at Dr. Ramón Madariaga Central Hospital (2005-2007) and 306 control mothers. Clinical and demographic information were collected from clinical records, and socioeconomic details were obtained by interview. Multivariable logistic regression was used to explore the relationships between congenital syphilis and clinical and socioeconomic factors. RESULTS: Receiving the recommended number of prenatal health checks had a clear protective effect on congenital syphilis in the univariate analysis (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.31-0.86), as did being in a stable relationship (OR 0.23, 95% CI 0.14-0.38). Furthermore, women with secondary education or above were over four-times less likely to have a child with congenital syphilis compared to women who had not completed primary school education, even after controlling for the number of prenatal health checks and other factors (adjusted OR 0.24, 95% CI 0.08-0.72). In addition, women with previous stillborn births were over three-times more likely to have a baby with congenital syphilis after controlling for education and prenatal care (adjusted OR 3.37, 95% CI 1.24-9.16). CONCLUSIONS: There is a clear opportunity for reducing the burden of congenital syphilis by promoting syphilis screening and treatment in women with previous stillborn births. In addition, the potential impact of more general policies addressing social determinants of health, such as those improving education, must not be overlooked.
IL-1ra Anti-inflammatory Cytokine Polymorphism is Associated with Risk of Gastric Cancer and Chronic Gastritis in a Brazilian Population, but the TNF-β Pro-inflammatory Cytokine is Not
Molecular Biology Reports. Feb, 2012 | Pubmed ID: 22327782
Genetic polymorphisms in genes that codify inflammatory cytokines have been associated with gastric carcinogenesis. This study evaluated polymorphisms IL-1RN VNTR and TNFB+252A/G in a population from Southeast Brazil with regard to the risk of chronic gastritis and gastric cancer and the presence of an association of gastric lesions with risk factors such as gender, age, smoking, drinking and Helicobacter pylori infection. In this case-control study, polymorphism at IL-1RN VNTR was investigated using the allele-specific polymerase chain reaction method, while the polymerase chain reaction-restriction fragment length polymorphism technique was used to identify the TNFB+252A/G genotype in 675 Brazilian individuals [229 with chronic gastritis (CG), 200 with gastric cancer (GC) and 246 healthy individuals as controls (C)]. Multiple logistic regression analysis (log-additive, dominant, and recessive models) have not showed association of the genotype frequencies for the SNP TNFB+252A/G with risk of CG or GC. However, as for IL-1RN VNTR it was observed significant differences in all three analysis models, with higher values of OR in recessive model, both in the GC group (OR = 3.04, 95% CI = 1.41-6.56, p < 0.01) and CG (OR = 2.32, 95% CI = 1.10-4.90, p = 0.02) compared to the C group. In addition, the multiple logistic regression showed also an association with risk factors such as male gender, older age and alcohol intake regarded GC group. So, our results indicated that the IL-1RN*2 allele may increase the risk of gastric cancer and precancerous lesions in the Southeast Brazilian population, reinforcing the importance of host genetic factors in the susceptibility to gastric cancer and the participation of cytokines in both the inflammation and the carcinogenic process.
American Journal of Primatology. Feb, 2012 | Pubmed ID: 22328205
Capuchin monkey behavior has been the focus of increasing numbers of captive and field studies in recent years, clarifying behavioral and ecological differences between the two morphological types: the gracile and the robust capuchins (also referred to as untufted and tufted). Studies have tended to focus on the gracile species Cebus capucinus (fewer data are available for C. albifrons, C. olivaceus, and C. kaapori) and on Cebus apella, a name that has encompassed all of the robust capuchins since the 1960s. As a result, it is difficult to ascertain the variation within either gracile or robust types. The phylogenetic relationships between gracile and robust capuchins have also, until now, remained obscure. Recent studies have suggested two independent Pliocene radiations of capuchins stemming from a common ancestor in the Late Miocene, about 6.2 millions of years ago (Ma). The present-day gracile capuchins most likely originated in the Amazon, and the robust capuchins in the Atlantic Forest to the southeast. Sympatry between the two types is explained by a recent expansion of robust capuchins into the Amazon (ca. 400,000 years ago). Morphological data also support a division of capuchins into the same two distinct groups, and we propose the division of capuchin monkeys into two genera, Sapajus Kerr, 1792, for robust capuchins and Cebus Erxleben, 1777, for gracile capuchins, based on a review of extensive morphological, genetic, behavioral, ecological, and biogeographic evidence.
Influence of Fatty Acids in Maternal Diet on Atherogenesis in Offspring of LDL Receptor-deficient Mice
International Journal of Clinical and Experimental Medicine. 2012 | Pubmed ID: 22328949
The present study investigated the effect of a maternal diet rich in omega-6 (E6D) or omega-9 (E9D) on atherogenesis in the offspring of mice.
Effect of Endogenous Hydrogen Sulfide Inhibition on Structural and Functional Renal Disturbances Induced by Gentamicin
Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica ... [et Al.]. Feb, 2012 | Pubmed ID: 22331137
Genetic Testing and Molecular Biomarkers. Feb, 2012 | Pubmed ID: 22304488
Background: The JAK2 V617F mutation is associated with three myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). It generates an unregulated clonal hematopoietic progenitor and leads to abnormal increased proliferation of one or more myeloid lineages. Subjects bearing this mutation may present more frequently with complications such as thrombosis and bleeding, and no specific treatment has yet been developed for BCR-ABL-negative JAK2 V617F-negative MPNs. Aims: To determine the prevalence of JAK2 V617F in MPNs in Pernambuco, Brazil, and to compare it with previous studies. Material and Methods: 144 blood samples were collected at the Hospital of Hematology of the HEMOPE Foundation and were genotyped by polymerase chain reaction-restriction fragment length polymorphism with BsaXI enzymatic digestion. Results and Discussion: 88% (46/52) of the patients with PV, 47% (39/81) with ET, and 77% (8/11) with PMF were positive for JAK2 V617F, while more than 35% of the individuals were JAK2 V617F-negative, confirming a high prevalence of this abnormality in MPNs, more frequently with a low mutated allele burden, similar to what has been reported in other Western countries, despite differences among methods used to detect this mutation. Screening for JAK2 V617F may allow specific management of these diseases with JAK2 inhibitors in the future and highlights the need for further studies on the pathogenesis of BCR-ABL-negative JAK2 V617F-negative MPNs.
Comparative Immunology, Microbiology and Infectious Diseases. Mar, 2012 | Pubmed ID: 22304900
Mycoplasma hyopneumoniae, the primary pathogen of enzootic pneumonia, is highly prevalent worldwide and causes major economic losses to the pig industry. Commercial vaccines are widely used in the control of this disease, however, they provide only partial protection. The aim of this study was to evaluate 34 recombinant proteins of M. hyopneumoniae expressed in Escherichia coli. Antigenic and immunogenic properties of these proteins were analyzed. For this, the proteins were tested against hyperimmune and convalescent pig sera through ELISA and Western blot. Immunogenicity of the recombinant proteins was evaluated in BALB/c mice following intramuscular inoculation. Most antigens were able to induce a strong immune response and sera from inoculated mice were able to recognize native proteins by cell ELISA and Western blot. Several recombinant proteins were specifically recognized by convalescent pig sera, indicating they are expressed during infection. These data may help to develop more efficacious vaccines against M. hyopneumoniae.
Veterinary Parasitology. Jan, 2012 | Pubmed ID: 22305116
Several studies have shown the benefit of the use of probiotics in the prevention and treatment of diseases; however, few of them have investigated the effect of probiotics on parasitosis. In this study, the effect of Saccharomyces boulardii on the intensity of infection of mice with toxocariasis was evaluated. The animals were fed with a diet supplemented with S. boulardii for 15 days before inoculation with Toxocara canis eggs and for 2 or 60 days post-inoculation. S. boulardii promoted a reduction of approximately 36% in the average number of recovered T. canis larvae, suggesting that it can be used as an alternative to help control toxocariasis.
BMC Complementary and Alternative Medicine. Feb, 2012 | Pubmed ID: 22305153
ABSTRACT: BACKGROUND: Dipteryx alata Vogel popularly known as "baru" is an important commercial leguminous tree species from the Brazilian Cerrado, which possess medicinal properties, besides its fruits consumption by animals and humans. The use of the "naturally occurring plants" as herbal remedies and foods mainly from leaves, seeds, flowers and roots of plants or extracts require precautions before ensuring these are safe and efficacious. The objective of this study was to evaluate the safety of D. alata barks extract. METHODS: Vegetal drugs of D. alata barks were submitted to quality control assays and further to the safety assays under 1) in vitro parameter by Salmonella (Ames) mutagenicity, and 2) in vivo parameter on the pregnancy of rats. RESULTS: The extract was non-mutagenic to any of the assessed strains TA97a, TA98, TA100 and TA102 even after metabolic activation (+S9). All in vivo parameters (reproductive ability evaluation, physical development of rat offsprings, and neurobehavioral development assays) showed no changes related to control group. CONCLUSION: D. alata barks extract is neither mutagenic by the Ames test nor toxic in the pregnancy of rats, with no physical-neurobehavioral consequences on the rat offsprings development.
Community Health Workers in Brazil's Unified Health System: A Framework of Their Praxis and Contributions to Patient Health Behaviors
Social Science & Medicine (1982). Jan, 2012 | Pubmed ID: 22305469
Community Health Workers (CHWs) play a pivotal role in primary care, serving as liaisons between community members and medical providers. However, the growing reliance of health care systems worldwide on CHWs has outpaced research explaining their praxis - how they combine indigenous and technical knowledge, overcome challenges and impact patient outcomes. This paper thus articulates the CHW Praxis and Patient Health Behavior Framework. Such a framework is needed to advance research on CHW impact on patient outcomes and to advance CHW training. The project that originated this framework followed Community-Based Participatory Research principles. A team of U.S.-Brazil research partners, including CHWs, worked together from conceptualization of the study to dissemination of its findings. The framework is built on an integrated conceptual foundation including learning/teaching and individual behavior theories. The empirical base of the framework comprises in-depth interviews with 30 CHWs in Brazil's Unified Health System, Mesquita, Rio de Janeiro. Data collection for the project which originated this report occurred in 2008-10. Semi-structured questions examined how CHWs used their knowledge/skills; addressed personal and environmental challenges; and how they promoted patient health behaviors. This study advances an explanation of how CHWs use self-identified strategies - i.e., empathic communication and perseverance - to help patients engage in health behaviors. Grounded in our proposed framework, survey measures can be developed and used in predictive models testing the effects of CHW praxis on health behaviors. Training for CHWs can explicitly integrate indigenous and technical knowledge in order for CHWs to overcome contextual challenges and enhance service delivery.
The Effects of Screw Length on Stability of Simulated Osteoporotic Distal Radius Fractures Fixed With Volar Locking Plates
The Journal of Hand Surgery. Feb, 2012 | Pubmed ID: 22305729
PURPOSE: Volar plating for distal radius fractures has caused extensor tendon ruptures resulting from dorsal screw prominence. This study was designed to determine the biomechanical impact of placing unicortical distal locking screws and pegs in an extra-articular fracture model. METHODS: We applied volar-locking distal radius plates to 30 osteoporotic distal radius models. We divided radii into 5 groups based on distal locking fixation: bicortical locked screws, 3 lengths of unicortical locked screws (abutting the dorsal cortex [full length], 75% length, and 50% length to dorsal cortex), and unicortical locked pegs. Distal radius osteotomy simulated a dorsally comminuted, extra-articular fracture. We determined each construct's stiffness under physiologic loads (axial compression, dorsal bending, and volar bending) before and after 1,000 cycles of axial conditioning and before axial loading to failure (2 mm of displacement) and subsequent catastrophic failure. RESULTS: Cyclic conditioning did not alter constructs' stiffness. Stiffness to volar bending and dorsal bending forces were similar between groups. Final stiffness (N/mm) under axial load was statistically equivalent for all groups: bicortical screws (230), full-length unicortical screws (227), 75% length unicortical screws (226), 50% length unicortical screws (187), and unicortical pegs (226). Force (N) at 2 mm displacement was significantly less for 50% length unicortical screws (311) compared with bicortical screws (460), full-length unicortical screws (464), 75% length unicortical screws (400), and unicortical pegs (356). Force (N) to catastrophic fracture was statistically equivalent between groups, but mean values for pegs (749) and 50% length unicortical (702) screws were 16% to 21% less than means for bicortical (892), full-length unicortical (860), and 75% length (894) unicortical constructs. CONCLUSIONS: Locked unicortical distal screws of at least 75% length produce construct stiffness similar to bicortical fixation. Unicortical distal fixation for extra-articular distal radius fractures should be entertained to avoid extensor tendon injury because this technique does not appear to compromise initial fixation. CLINICAL RELEVANCE: Using unicortical fixation during volar distal radius plating may protect extensor tendons without compromising fixation.
Thermal Activated Energy Transfer Between Luminescent States of Mn(2+)-doped ZnTe Nanoparticles Embedded in a Glass Matrix
Physical Chemistry Chemical Physics : PCCP. Feb, 2012 | Pubmed ID: 22307452
Zn(1-x)Mn(x)Te nanocrystals (NCs), at various concentrations x, were successfully grown in a host glass matrix by the fusion method after appropriate annealing. Growth of these NCs was evidenced by optical absorption (OA), X-Ray Diffraction (XRD), magnetic force microscopy (MFM) and photoluminescence (PL) measurements. From the room temperature OA spectra, it was possible to observe the formation of two well defined, different sized groups of NCs, one attributed to quantum dots (QDs) and the other to bulk-like nanocrystals (NCs). XRD results have confirmed that the cubic zincblend structure of nanoparticles is not altered by the substitutional incorporation of Mn(2+) ions into the ZnTe NCs. MFM images supported the OA spectra results and thus provided additional confirmation of the formation of Zn(1-x)Mn(x)Te magnetic nanoparticles in the host glass matrix. The two groups of NCs were also observed in the PL spectra as well as deep defects attributed to the presence of oxygen centers in the electronic structure of the Zn(1-x)Mn(x)Te NCs. Strong agreement between the fitting model, based on rate equation, and experimental PL intensity data at different temperatures demonstrates that this model adequately describes the energy transfer processes between the NCs and the defects of the Zn(1-x)Mn(x)Te system at different temperatures.
American Journal of Medical Genetics. Part A. Mar, 2012 | Pubmed ID: 22307742
Adams-Oliver syndrome (AOS) is a rare condition defined by combination of cutis aplasia and transverse limb abnormalities. Some authors have described a possible association between this syndrome and portal hypertension (PH) due to hepatoportal sclerosis (HPS). We present a boy with AOS who developed a progressive splenomegaly and hypersplenism at the age of 2 months, and was admitted for acute gastrointestinal bleeding (GI) at the age of 9 months. Subsequently, we documented an extrahepatic portal vein obstruction and esophageal varices. After several episodes of cataclysmic upper GI bleeding a mesentero-portal shunt (MPS) was performed at 10 months. The shunt thrombosed, and after three failed attempts of thrombectomy, it was removed. One month later a splenorenal shunt was performed, and this closed spontaneously by 3 years. The patient suffered from ischemic stroke after placing the first shunt, and has spastic diplegia, left frontal lobe epilepsy, hyperactivity and attention deficit disorder, and severe psychomotor delay. At 11 years and he presented with chronic liver failure and hyperammonemia and coagulopathy. We hypothesize that there may be an early embryonic vascular abnormality (vascular disruption) that may explain these vascular phenomena. © 2012 Wiley Periodicals, Inc.
Exposure Assessment of Pesticides in a Shallow Groundwater of the Tagus Vulnerable Zone (Portugal): a Multivariate Statistical Approach (JCA)
Environmental Science and Pollution Research International. Feb, 2012 | Pubmed ID: 22307895
PURPOSE: To assess groundwater exposure to pesticides, in agricultural areas of 'Ribatejo' region (Portugal), and the influence of some key factors in that exposure, field, laboratory and modelling studies were carried out. METHODS: The study was performed in maize, potato, sugar beet, tomato and vegetables agricultural areas, located in a shallow aquifer, with pesticides use and, in most cases, with irrigation practices. Pesticides used in the studied agricultural areas and having leaching potential were selected, being considered also other pesticides included in priority lists, defined in Europe. Evaluation of groundwater exposure to pesticides was carried out by successively: (1) groundwater sampling in seven campaigns over the period 2004-2006; (2) pesticide analysis [including isolation and concentration from the groundwater samples and further determination by gas chromatography-mass spectrometry (GC-MS) of 14 herbicides, four insecticides and two metabolites]; and (3) analysis and discussion of the results by applying joint correspondence analysis (JCA). RESULTS: From the 20 pesticides and metabolites selected for the study, 11 were found in groundwater. Pesticides and metabolites most frequently detected were atrazine, alachlor, metolachlor, desethylatrazine, ethofumesate, α-endosulfan, metribuzine, lindane and β-endosulfan. The results showed that groundwater exposure to pesticides is influenced by local factors-either environmental or agricultural, as precipitation, soil, geology, crops and irrigation practices. Spring and autumn were more associated with the detection of pesticides being more likely to observe mixtures of these compounds in a groundwater sample in these transition seasons. CONCLUSIONS: This work evidences the importance of models, which evaluate pesticides environmental behaviour, namely their water contamination potential (as Mackay multicompartimental fugacity model) and, specially, groundwater contamination potential (as GUS and Bacci and Gaggi leaching indices), in pesticide selection. Moreover, it reveals the importance to adapt proper statistical methods according to level of left-censored data. Using JCA was still possible to establish relations between pesticides and their temporal trend in a case study where there were more than 80% of data censored. This study will contribute to the Tagus river basin management plan with information on the patterns of pesticide occurrence in the alluvial aquifer system.
Pharmacokinetic Study of Vitreous and Serum Concentrations of Triamcinolone Acetonide After Posterior Sub-Tenon's Injection
American Journal of Ophthalmology. Feb, 2012 | Pubmed ID: 22310078
PURPOSE: To compare a theoretical pharmacokinetic model of triamcinolone acetonide after posterior sub-Tenon's injection with experimental serum and undiluted vitreous triamcinolone acetonide concentrations obtained during pars plana vitrectomy. DESIGN: Clinical-practice, prospective, interventional case series study. METHODS: This study compared computer-modeled triamcinolone acetonide diffusion after posterior sub-Tenon's injection with triamcinolone acetonide levels in experimental undiluted vitreous and serum samples from 57 patients undergoing vitrectomy assessed via mass spectrometry and high-pressure liquid chromatography. At least 5 pairs of samples were collected at each of 7 time points (1 day, 3 days, and 1, 2, 3, 4, and 8 weeks) after triamcinolone acetonide injection, with 6 controls without injection. Cortisol levels were measured in 31 sets of samples. RESULTS: The theoretical model predicted that triamcinolone acetonide levels in systemic blood, vitreous, and choroidal extracellular matrix would plateau after 3 days at 15 ng/mL, 227 ng/mL and 2230 ng/mL, respectively. Experimental vitreous levels of triamcinolone peaked at 111 ng/mL at day 1, then reached a plateau in the range 15 to 25 ng/mL, while serum triamcinolone levels peaked at day 3 near 35 ng/mL and plateaued near 2 to 8 ng/mL. Serum triamcinolone and cortisol levels were inversely correlated (Spearman -0.42, P = .02). CONCLUSIONS: The theoretical model predicts efficient delivery of triamcinolone acetonide from the posterior sub-Tenon's space to the extracellular choroidal matrix. The experimental findings demonstrate low levels of serum triamcinolone that alter systemic cortisol levels and higher vitreous levels lasting at least 1 month. Both assessments support trans-scleral delivery of posterior sub-Tenon's triamcinolone.
New PCR Assays for the Identification of Fusarium Verticillioides, Fusarium Subglutinans, and Other Species of the Gibberella Fujikuroi Complex
International Journal of Molecular Sciences. 2012 | Pubmed ID: 22312242
Fusarium verticillioides and Fusarium subglutinans are important fungal pathogens of maize and other cereals worldwide. In this study, we developed PCR-based protocols for the identification of these pathogens targeting the gaoB gene, which codes for galactose oxidase. The designed primers recognized isolates of F. verticillioides and F. subglutinans that were obtained from maize seeds from several producing regions of Brazil but did not recognize other Fusarium spp. or other fungal genera that were either obtained from fungal collections or isolated from maize seeds. A multiplex PCR protocol was established to simultaneously detect the genomic DNA from F. verticillioides and F. subglutinans. This protocol could detect the DNA from these fungi growing in artificially or naturally infected maize seeds. Another multiplex reaction with a pair of primers developed in this work combined with a pre-existing pair of primers has allowed identifying F. subglutinans, F. konzum, and F. thapsinum. In addition, the identification of F. nygamai was also possible using a combination of two PCR reactions described in this work, and another described in the literature.
Filler Morphology of Resin-based Low-viscosity Materials and Surface Properties After Several Photoactivation Times
Acta Odontologica Scandinavica. Jan, 2012 | Pubmed ID: 22283452
Abstract Aim. This study aimed to characterize the morphology of filler particles and to analyze the effect of shortened and extended photoactivation times on hardness (VHN) and cross-link density (CLD) of resin-based low-viscosity materials. Methods. Sixteen commercially available materials were tested: four fissure sealants (Alpha Seal, Fluroshield Yellowed, Bioseal and Fluroshield White) and 12 flowable composites (Opallis T, Permaflo T, Opallis A2, Natural Flow A2, Master Flow A2, Permaflo A2, Filtek Z350 A2, Natural Flow O, Master Flow OA2, Opallis OA3.5, Filtek Z350 OA3, Opallis OP) at six curing times (10 s, 20 s, 30 s, 40 s, 50 s and 60 s). Specimens were fabricated (n = 5), analyzed by Scanning Electron Microscopy, by VHN and by CLD. Results. Unimodal and multimodal filler particles sizes with spherical and irregular shapes were observed. Unfilled materials were also detected. There were no differences among curing times for either VHN or CLD. Opallis A2 and Opallis OA3.5 showed the highest VHN at all curing times, whereas Master Flow A2 and Master Flow OA2 presented the lowest VHN. Opallis A2 presented the highest CLD at all curing times and Alpha Seal showed the lowest CLD. Conclusions. Filler particle morphology differed among the resin-based low-viscosity materials tested. The shortest photoactivation time tested could yield similar VHN and CLD means to those provided by the most extended photoactivation time.
Current Pharmaceutical Design. Jan, 2012 | Pubmed ID: 22283774
Recent data support the idea that the effects of RAS are not restricted to the cardiovascular and renal systems. Importantly, RAS modulates free radical production and the cellular synthesis of several molecules such as cytokines, chemokines and transcription factors. These functions reflect directly the RAS ability to modulate the cell growth, senescence and migration. Activation of the classic RAS, ACE/Ang II/AT1R, has been strictly related to down regulation of pro-survival genes (Nampt and Sirt3), increase in ROS production and pro-inflammatory cytokines and chemokines release, leading to cell senescence, inflammation and development of autoimmune dysfunctions. However, the new view of RAS, point to the ACE2/Ang-(1-7)/Mas receptor axis as a counter-regulator of the effects of the classic Ang II-mediated effects. This new pathway is not totally elucidated. However some studies suggest an important role of this novel axis in the control of cytokines release as well cell migration and synthesis, preventing extra-cellular matrix deposition and cell apoptosis. Classic RAS blockers have been proposed as anti-inflammatory and immunomodulatory agents and some studies suggest a new potential application of RAS blockers in autoimmune diseases. The aim of the present review is to update the novel roles of classical and new RAS components and their possible implication during the physiological aging, in the immune system and inflammation.
C677T and A1298C Polymorphisms of MTHFR Gene and Their Relation to Homocysteine Levels in Turner Syndrome
Genetic Testing and Molecular Biomarkers. Jan, 2012 | Pubmed ID: 22283972
Aims: To determine the frequency of C677T and A1298C polymorphisms of the MTHFR gene and correlate them with homocysteine serum levels in patients with Turner syndrome (TS) and controls. Methods: This case-control study included 78 women with TS and a control group of 372 healthy individuals without personal or family history of cardiovascular disease and cancer. C677T (rs1801133) and A1298C (rs1801131) polymorphisms were detected by polymerase chain reaction-restriction fragment-length polymorphism and the TaqMan system, respectively. Homocysteine serum levels were determined by high-performance liquid chromatography. The results were analyzed statistically, and p<0.05 was considered to represent a significant difference. Results: The homocysteine levels change was 13.9+3.3 nM in patients with TS and 8.8+3.2 nM in the control group. No significant difference between groups was found (p=0.348). Single-marker analysis revealed no association between MTHFR C677T polymorphism and TS when genotype (p=0.063) or allelic (p=0.277) distribution was considered. Regarding MTHFR A1298C polymorphism, a statistical difference was found between the TS group and the control group, for both genotype (p<0.0001) and allele (p<0.0001) distribution. Haplotype analysis of 2 MTHFR polymorphisms identified 2 haplotypes-CC and TC-associated with TS (p<0.001 and p=0.0165, respectively). However, homocysteine levels were not higher in patients with haplotype risk. Conclusion: The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS.
American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. Feb, 2012 | Pubmed ID: 22284282
Cytokines and chemokines regulate bone remodeling during orthodontic tooth movement. CC chemokine ligand 2 (CCL2) is involved in osteoclast recruitment and activity, and its expression is increased in periodontal tissues under mechanical loading. In this study, we investigated whether the CC chemokine receptor 2 (CCR2)-CCL2 axis influences orthodontic tooth movement.
Development and Analytical Validation of a Multivariate Calibration Method for Determination of Amoxicillin in Suspension Formulations by Near Infrared Spectroscopy
Talanta. Jan, 2012 | Pubmed ID: 22284501
This paper proposes a new method for determination of amoxicillin in pharmaceutical suspension formulations, based on transflectance near infrared (NIR) measurements and partial least squares (PLS) multivariate calibration. A complete methodology was implemented for developing the proposed method, including an experimental design, data preprocessing by using multiple scatter correction (MSC) and outlier detection based on high values of leverage, and X and Y residuals. The best PLS model was obtained with seven latent variables in the range from 40.0 to 65.0mgmL(-1) of amoxicillin, providing a root mean square error of prediction (RMSEP) of 1.6mgmL(-1). The method was validated in accordance with Brazilian and international guidelines, through the estimate of figures of merit, such as linearity, precision, accuracy, robustness, selectivity, analytical sensitivity, limits of detection and quantitation, and bias. The results for determinations in four commercial pharmaceutical formulations were in agreement with the official high performance liquid chromatographic (HPLC) method at the 99% confidence level. A pseudo-univariate calibration curve was also obtained based on the net analyte signal (NAS). The proposed chemometric method presented the advantages of rapidity, simplicity, low cost, and no use of solvents, compared to the principal alternative methods based on HPLC.
Solid Phase Microextraction, Mass Spectrometry and Metabolomic Approaches for Detection of Potential Urinary Cancer Biomarkers-A Powerful Strategy for Breast Cancer Diagnosis
Talanta. Jan, 2012 | Pubmed ID: 22284503
A sensitive assay to identify volatile organic metabolites (VOMs) as biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. Therefore the aim of this study was to establish the urinary metabolomic profile of breast cancer patients and healthy individuals (control group) and to explore the VOMs as potential biomarkers in breast cancer diagnosis at early stage. Solid-phase microextraction (SPME) using CAR/PDMS sorbent combined with gas chromatography-mass spectrometry was applied to obtain metabolomic information patterns of 26 breast cancer patients and 21 healthy individuals (controls). A total of seventy-nine VOMs, belonging to distinct chemical classes, were detected and identified in control and breast cancer groups. Ketones and sulfur compounds were the chemical classes with highest contribution for both groups. Results showed that excretion values of 6 VOMs among the total of 79 detected were found to be statistically different (p<0.05). A significant increase in the peak area of (-)-4-carene, 3-heptanone, 1,2,4-trimethylbenzene, 2-methoxythiophene and phenol, in VOMs of cancer patients relatively to controls was observed. Statiscally significant lower abundances of dimethyl disulfide were found in cancer patients. Bioanalytical data were submitted to multivariate statistics [principal component analysis (PCA)], in order to visualize clusters of cases and to detect the VOMs that are able to differentiate cancer patients from healthy individuals. Very good discrimination within breast cancer and control groups was achieved. Nevertheless, a deep study using a larger number of patients must be carried out to confirm the results.
Talanta. Jan, 2012 | Pubmed ID: 22284504
In recent years, the release of information about the preventative and curative properties of garlic on different diseases and their benefits to human health has led to an increase in the consumption of garlic. To meet the requirements of international markets and reach competitiveness and profitability, farmers seek to extend the offer period of fresh garlic by increasing post-harvest life. As a result, the use of maleic hydrazide (1,2-dihydropyridazine-3,6-dione) [MH], a plant growth regulator, has been widespread in various garlic growing regions of the world. The present work was undertaken to develop and validate a new analytical procedure based on MH extraction from garlic previously frozen by liquid nitrogen and submitted to low temperature clean-up. The applicability of the method by analysis of garlic samples from a commercial plantation was also demonstrated. The influence of certain factors on the performance of the analytical methodology were studied and optimized. The approach is an efficient extraction, clean-up and determination alternative for MH residue-quantification due to its specificity and sensitivity. The use of liquid nitrogen during the sample preparation prevents the degradation of the analyte due to oxidation reactions, a major limiting factor. Moreover, the method provides good linearity (r(2): 0.999), good intermediate precision (coefficient of variation (CV): 8.39%), and extracts were not affected by the matrix effect. Under optimized conditions, the limit of detection (LOD) (0.33mgkg(-1)) was well below the maximum residue level (MRL) set internationally for garlic (15mgkg(-1)), with excellent rates of recovery (over 95%), good repeatability and acceptable accuracy (CV averaged 5.74%), since garlic is a complex matrix. The analytical performance of the methodology presented was compared with other techniques already reported, with highly satisfactory results, lower LOD and higher recoveries rates. In addition, the extraction process is simple, not expensive, easily executable and requires lower volumes of organic solvent. The proposed methodology removes the need of extensive typical laboratory extraction procedures, reducing the amount of time needed for pesticide analysis and increasing sample throughput. Adopting this method gives food safety laboratories the potential to increase cost savings by a suitable technique in routine testing to determine MH residues in garlic.
Influence of HLA Alleles in Response to Treatment with Pegylated Interferon-alpha and Ribavirin in Patients with Chronic Hepatitis C
International Journal of Immunogenetics. Jan, 2012 | Pubmed ID: 22284614
The objective of this study was to analyse the possible role of HLA polymorphism of chronically infected hepatitis C virus patients in the response outcome to treatment with pegylated interferon-alpha plus ribavirin. To that end, 144 Brazilian patients infected only with genotype 1 of the virus were treated with pegylated interferon-alpha at 1.5 μg kg(-1) in conjunction with ribavirin (1000 mg if patient weight was <75 kg and 1250 mg if >75 kg) for 48 weeks. The patients did not have concomitant HBV or HIV infections or liver disease, did not undergo previous antiviral treatment, and were followed up for 24 weeks after the end of treatment to assure they presented a sustained virological response. Patients were classified according to response to treatment in responsive (SVR), nonresponsive (NRS) and relapsers (REL). HLA class I and class II typing were carried out through PCR-SSO using Luminex technology. A statistically higher frequency of DRB1*11 patients was observed in the SVR group (39.6% vs. 14.3%P = 0.0012; Pc = 0.0156; OR = 3.94; 95% CI = 1.8-8.8). HLA-DQB1*03 patients were also more frequent in the SVR group, but the P value lost significance after Bonferroni correction (62.3% vs. 41.7%P = 0.024; Pc = 0.14, OR = 2.3; 95% CI = 1.14-4.60). HLA class II antigens can positively influence the response to treatment with pegylated interferon-alpha and ribavirin.
Serological Profile of Buffalo (Bubalus Bubalis) Female Calves Vaccinated with Standard Brucella Abortus Strain 19 Vaccine Using Rose Bengal, 2-mercaptoethanol and Complement Fixation Tests
Biologicals : Journal of the International Association of Biological Standardization. Jan, 2012 | Pubmed ID: 22284623
The serological profiles of 21 female buffaloes vaccinated between 3 and 8 months of age using Brucella abortus strain 19 (S19) were evaluated by rose bengal (RBT), 2-mercaptoethanol (2ME) and complement fixation (CFT) tests. The serum strains were collected in day zero, 15, 30, 45, 60th days and subsequently to each 30 months, until 720th day after vaccination. No animal showed reaction in day zero. In 15th day above 95% of animals revealed reaction in all tests. All the animals presented absence of reactions in CFT, RBT and 2ME tests at 270, 300 and 360 days after vaccination, respectively. Our finding highlighted early response in CFT compared than other conventional agglutination tests. None of animals presented oscillation of titers or reactions in any test after 360 day of study, which enables the use of these tests after this period without interference of antibodies from S19 vaccine origin between 3 and 8 months in buffalo heifers.
American Journal of Human Genetics. Feb, 2012 | Pubmed ID: 22284828
A major unanswered question regarding the dispersal of modern humans around the world concerns the geographical site of the first human steps outside of Africa. The "southern coastal route" model predicts that the early stages of the dispersal took place when people crossed the Red Sea to southern Arabia, but genetic evidence has hitherto been tenuous. We have addressed this question by analyzing the three minor west-Eurasian haplogroups, N1, N2, and X. These lineages branch directly from the first non-African founder node, the root of haplogroup N, and coalesce to the time of the first successful movement of modern humans out of Africa, ∼60 thousand years (ka) ago. We sequenced complete mtDNA genomes from 85 Southwest Asian samples carrying these haplogroups and compared them with a database of 300 European examples. The results show that these minor haplogroups have a relict distribution that suggests an ancient ancestry within the Arabian Peninsula, and they most likely spread from the Gulf Oasis region toward the Near East and Europe during the pluvial period 55-24 ka ago. This pattern suggests that Arabia was indeed the first staging post in the spread of modern humans around the world.
Interleukin 18 Messenger RNA and ProIL-18 Protein Expression in Chorioamniotic Membranes from Pregnant Women with Preterm Prelabor Rupture of Membranes
European Journal of Obstetrics, Gynecology, and Reproductive Biology. Jan, 2012 | Pubmed ID: 22285684
OBJECTIVE: To quantify the expression of IL-18 mRNA and protein in the chorioamniotic membranes of pregnant women with PPROM and correlate expression with histological chorioamnionitis. STUDY DESIGN: A case control study that included 42 pregnant women not in labor in the following groups: PPROM (n=28) and controls with intact membranes submitted to selective cesarean section at term (n=14). Expression of IL-18 mRNA in chorioamniotic membranes was determined by real-time polymerase chain reaction, and IL-18 protein expression was measured by western blot. Histopathological analyses and immunolocalization of IL-18 by immunohistochemistry were also performed. Analyses were performed using the Mann-Whitney or Fisher's exact tests and the group effect was considered significant if the adjusted p-values were <0.05 and the magnitude of change was greater than 2-fold for mRNA expression. RESULTS: IL-18 mRNA was present in 100% of samples and no difference in expression was observed between term vs. PPROM membranes (fold-change 0.12; p=0.88). In the PPROM group, no difference was observed in IL-18 mRNA regarding gestational age (fold-change 0.11; p=0.42) or the presence of histological chorioamnionitis (fold-change 0.26; p=0.15). ProIL-18 was present in all samples. IL-18 was immunolocalized to amnion, chorion and decidua cells, with intense immunohistochemical staining at the choriodecidual junction. CONCLUSION: Chorioamniotic membranes are sources of IL-18 mRNA and proIL-18, and their expression is unrelated to PPROM or histological chorioamnionitis.
Virulence. Jan, 2012 | Pubmed ID: 22286707
Escherichia coli represents a major cause of morbidity and mortality worldwide. The treatment of E. coli infections is now threatened by the emergence of antimicrobial resistance. The dissemination of resistance is associated with genetic mobile elements, such as plasmids, that may also carry virulence determinants. A proficient pathogen should be virulent, resistant to antibiotics, and epidemic. However, the interplay between resistance and virulence is poorly understood. This review aims to critically discuss the association and linked transmission of both resistance and virulence traits in strains from extraintestinal infections in E. coli, and intestinal pathotypes. Despite the numerous controversies on this topic, findings from research published to date indicate that there is a link between resistance and virulence, as illustrated by the successful E. coli ST131 epidemic clone. Perhaps the most commonly accepted view is that resistance to quinolones is linked to a loss of virulence factors. However, the low virulent phylogenetic groups might be more prone to acquire resistance to quinolones. Specific characteristics of the E. coli genome that have yet to be identified may contribute to such genetic linkages. Research based on bacterial populations is sorely needed to help understand the molecular mechanisms underlying the association between resistance and virulence, that, in turn, may help manage the future disseminations of infectious diseases in their entirety.
The Histone-like Nucleoid Structuring Protein (H-NS) is a Repressor of Vibrio Cholerae Exopolysaccharide Biosynthesis (vps) Genes
Applied and Environmental Microbiology. Jan, 2012 | Pubmed ID: 22287003
The capacity of Vibrio cholerae to form biofilms has been shown to enhance its survival in the aquatic environment and play important roles in pathogenesis and disease transmission. In this study we demonstrate that the histone-like nucleoid structuring protein is a repressor of exopolysaccharide (vps) biosynthesis genes and biofilm formation.
Spasmolytic Activity of Trachylobanes Ent-7α-acetoxytrachyloban-18-oic Acid and Ent-7α-hydroxytrachyloban-18-oic Acid Isolated from Xylopia Langsdorfiana A. St-Hil. & Tul. (Annonaceae)
Natural Product Research. Jan, 2012 | Pubmed ID: 22288518
We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.
Biomacromolecules. Feb, 2012 | Pubmed ID: 22288730
Dextrin, a glucose polymer with low molecular weight, was used to develop a fully resorbable hydrogel, without using chemical initiators. Dextrin was first oxidized (oDex) with sodium periodate and then cross-linked with adipic acid dihidrazide, a nontoxic cross-linking molecule. Furthermore, a new bidimensional composite hydrogel, made of oxidized dextrin incorporating dextrin nanogels (oDex-nanogel), was also developed. The oDex hydrogels showed good mechanical properties and biocompatibility, allowing the proliferation of mouse embryo fibroblasts 3T3 cultured on top of the gel. The gelation time may be controlled selecting the concentrations of the polymer and reticulating agent. Both the oDex and oDex-nanogel hydrogels are biodegradable and present a 3-D network with a continuous porous structure. The obtained hybrid hydrogel enables the release of the dextrin nanogel over an extended period of time, paralleling the mass loss curve due to the degradation of the material. The dextrin nanogel allowed the efficient incorporation of interleukin-10 and insulin in the oDex hydrogel, providing a sophisticated system of controlled release. The new hydrogels present promising properties as an injectable carrier of bioactive molecules. Both proteins and poorly water-soluble low-molecular-weight drugs are efficiently encapsulated in the nanogel, which performs as a controlled release system entrapped in the hydrogel matrix.
Retinal Pigment Epithelial Cells Use a MerTK-dependent Mechanism to Limit the Phagocytic Particle Binding Activity of αvβ5 Integrin
Biology of the Cell / Under the Auspices of the European Cell Biology Organization. Jan, 2012 | Pubmed ID: 22289110
BACKGROUND INFORMATION: αvβ5 integrin and Mer tyrosine kinase (MerTK) receptors reside at the apical surface of the retinal pigment epithelium (RPE) in the eye to promote the diurnal, synchronized phagocytosis of shed photoreceptor outer segment fragments (POS) that is critical for vision. Phagocytosis assays studying RPE cells in culture have defined roles for αvβ5 in POS surface binding and for MerTK in engulfment of bound POS. Both receptors have thus far only been studied separately. It is therefore unknown if αvβ5 integrin activity in POS binding is independent of the engulfment function of RPE cells. This study investigates how increasing αvβ5 receptor levels affects POS binding and internalization by wild-type, αvβ5- or MerTK-deficient RPE. RESULTS: β5 integrin-green fluorescent protein (β5-GFP) fusion proteins formed heterodimeric receptors with endogenous αv integrin subunits at the apical surface of mouse or rat RPE cells that co-immunoprecipitated focal adhesion kinase and redistributed with bound POS like endogenous αvβ5 receptors. In β5(-/-) RPE cells, de novo formation of αvβ5-GFP receptors restored POS binding and internalization up to but not above wild-type POS uptake levels. In wild-type RPE cells, increasing levels of αvβ5 surface receptors by overexpressing β5-GFP only moderately stimulated POS binding even if POS internalization was inhibited pharmacologically or by lowering incubation temperatures. In contrast, the same increase in αvβ5 receptor levels dramatically enhanced POS binding of RPE cells lacking MerTK. Furthermore, decreasing MerTK expression by RNA interference increased POS binding to endogenous αvβ5 receptors of wild-type RPE cells. CONCLUSIONS: Expressing β5-GFP is sufficient to reverse phagocytic deficiencies of RPE cells derived from β5(-/-) mice indicating that these cells do not irreversibly lose other components of the phagocytic machinery. RPE cells expressing the engulfment receptor MerTK control POS binding by limiting activity of endogenous αvβ5 and αvβ5-GFP integrins although they reside at the apical, phagocytic surface. In contrast, RPE cells permanently or transiently losing MerTK expression lack this regulatory mechanism and bind excess POS via surface αvβ5 receptors. Taken together, these data reveal a novel feedback mechanism that restricts binding of POS to surface avb5 integrin receptors in RPE cells.
A Randomized Study of Tenofovir Disoproxil Fumarate in Treatment-Experienced Human Immunodeficiency Virus-1 Infected Adolescents
The Pediatric Infectious Disease Journal. Feb, 2012 | Pubmed ID: 22301477
BACKGROUND:: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS:: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to < 18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean 216.8 mg/m) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at Week 24. RESULTS:: Eighty-seven subjects (45 TDF, 42 placebo) received study drug. Through Week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log10copies/ml, P=0.55). The percentages of subjects who achieved HIV-1 RNA < 400 copies/ml were similar at Week 24 (40.9% versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4% versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9% versus 33.3%). TDF was generally safe and well-tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the two groups. CONCLUSION:: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population.
Tachyphylaxis to the Sumatriptan-Induced Contractile Effect in the Human Uterine Artery but Not in Human Cerebral Blood Vessels: Pharmacological Demonstration of the 5-HT(1B) Receptor Functionality Loss
Pharmacology. Feb, 2012 | Pubmed ID: 22302025
The in vitro contractile response of the human uterine artery to sumatriptan was compared to that of human cerebral blood vessels. Artery rings were prepared for isometric contraction. Tachyphylaxis to the triptan-induced vascular contraction was observed in the uterine artery, but not in basilar and middle cerebral arteries. To evaluate 5-HT(1) receptor subtypes functionality, concentration-response curves to sumatriptan were performed at 0 and 24 h after uterine artery isolation. Both 10 μmol/l cyanopindolol and 63 nmol/l SB 224,289 (5-HT(1B) receptor antagonists) significantly antagonized the contractile response induced by sumatriptan at 0 h but not after 24 h of uterine artery isolation. The 5-HT(1B/1D) receptor antagonist BRL 15,572 at 10 μmol/l significantly antagonized the sumatriptan contractile response at both experimental conditions. We conclude that the tachyphylaxis to sumatriptan observed in the non-cerebral blood vessels, and not in the cerebral ones, may be due to loss of functionality of the 5-HT(1B) receptor subtype, increasing the safety of triptans.
Journal of Dental Research. Feb, 2012 | Pubmed ID: 22302144
Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post-transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3'-untranslated regions (3'UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3'UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.
Accuracy and Measures of Association of Anthropometric Indexes of Obesity to Identify the Presence of Hypertension in Adults: a Population-based Study in Southern Brazil
European Journal of Nutrition. Feb, 2012 | Pubmed ID: 22302615
PURPOSE: This study proposes to examine the accuracy of four anthropometric indexes of obesity to identify the presence of hypertension and assess differences in the estimation and strength of effect measures of the association between each anthropometric measure and hypertension in Brazilian adults. METHODS: A population-based cross-sectional study was carried out with a sample of 1,720 adults from Florianópolis, Brazil. Receiver operating characteristic (ROC) curves were performed to identify the sensitivity and specificity of the best cutoff values for anthropometric indexes (body mass index-BMI, waist circumference-WC, waist-to height ratio-WHtR and conicity index-C-index) for prediction of hypertension. The associations between anthropometric indexes and hypertension were analyzed by Poisson regression expressed as Prevalence Ratios (95% CI) adjusted for socio-demographic variables, health behavior, height, and anthropometric indexes. RESULTS: Of the four anthropometric indexes studied, BMI, WC, and WHtR were found to have the largest areas under the ROC curve relative to hypertension in both sexes. The cutoff values in women and men associated with presence of hypertension were BMI of 24.9 and 24.6 kg/m², WC of 86.2 and 89.5 cm, WHtR of 0.49 and 0.50, and C-index of 1.15 and 1.18, respectively. WC and BMI had greater magnitude of association with presence of hypertension, adjusting for socio-demographic variables, health behavior, height, and anthropometric indexes in women and men, respectively. CONCLUSIONS: Anthropometric indexes provide an effective, simple, inexpensive, and non-invasive means for a first-level screening for hypertension.
Chromenopyrazoles: Non-psychoactive and Selective CB(1) Cannabinoid Agonists with Peripheral Antinociceptive Properties
ChemMedChem. Feb, 2012 | Pubmed ID: 22302767
The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB(1) -mediated side effects are due to the fact that CB(1) receptors are largely expressed in the central nervous system (CNS). As it is known that CB(1) receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB(1) and CB(2) receptors. Structural features required for CB(1) /CB(2) affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB(1) ligands. These modeling studies suggest that full CB(1) selectivity over CB(2) can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. In vivo behavioral tests were then carried out on the most effective CB(1) cannabinoid agonist, 13 a. Chromenopyrazole 13 a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13 a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot-plate test, the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms.
Emerging Infectious Diseases. Feb, 2012 | Pubmed ID: 22304972
Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults.
Comparative Sensitivity of Computed Tomography Vs. Magnetic Resonance Imaging for Detecting Acute Posterior Fossa Infarct
The Journal of Emergency Medicine. Feb, 2012 | Pubmed ID: 22305149
BACKGROUND: Posterior fossa strokes, particularly those related to basilar occlusion, pose a high risk for progression and poor neurological outcomes. The clinical history and examination are often not adequately sensitive or specific for detection. STUDY OBJECTIVES: Because this population stands to benefit from acute interventions such as intravenous and intra-arterial tissue plasminogen activator, mechanical thrombectomy, and intensive monitoring for neurologic deterioration, this study examined the sensitivity of non-contrast head computed tomography (NCCT) for diagnosing posterior fossa strokes in the emergency department. METHODS: This study analyzed a prospectively collected database of acute ischemic stroke patients who underwent head NCCT within 30h of symptom onset and who were subsequently found to have a posterior fossa infarct on brain magnetic resonance imaging (MRI) performed within 6h of the NCCT. RESULTS: There were 67 patients identified who had restricted diffusion on MRI in the posterior fossa. The National Institutes of Health Stroke Scale (NIHSS) scores ranged from 0 to 36, median 3. Only 28 patients had evidence of infarction on the initial NCCT scan. The timing of NCCT scans ranged from 1.2 to 28.9h after symptom onset. The sensitivity of NCCT was 41.8% (95% confidence interval 30.1-54.4). The longest period of time between symptom onset and a negative NCCT with a subsequent positive diffusion-weighted imaging MRI was 26.7h. CONCLUSIONS: Head NCCT imaging is frequently insensitive for detecting posterior fossa infarction. Temporal evolution of strokes in this distribution, coupled with beam-hardening artifact, may contribute to this limitation. When a posterior fossa stroke is suspected and the NCCT is non-diagnostic, MRI is the preferred imaging modality to exclude posterior fossa infarction.
Development of a Novel Microextraction by Packed Sorbent-based Approach Followed by Ultrahigh Pressure Liquid Chromatography As a Powerful Technique for Quantification Phenolic Constituents of Biological Interest in Wines
Journal of Chromatography. A. Jan, 2012 | Pubmed ID: 22305355
A novel analytical approach, based on a miniaturized extraction technique, the microextraction by packed sorbent (MEPS), followed by ultrahigh pressure liquid chromatography (UHPLC) separation combined with a photodiode array (PDA) detection, has been developed and validated for the quantitative determination of sixteen biologically active phenolic constituents of wine. In addition to performing routine experiments to establish the validity of the assay to internationally accepted criteria (linearity, sensitivity, selectivity, precision, accuracy), experiments are included to assess the effect of the important experimental parameters on the MEPS performance such as the type of sorbent material (C2, C8, C18, SIL, and M1), number of extraction cycles (extract-discard), elution volume, sample volume, and ethanol content, were studied. The optimal conditions of MEPS extraction were obtained using C8 sorbent and small sample volumes (250μL) in five extraction cycle and in a short time period (about 5min for the entire sample preparation step). The wine bioactive phenolics were eluted by 250μL of the mixture containing 95% methanol and 5% water, and the separation was carried out on a HSS T3 analytical column (100mm×2.1mm, 1.8μm particle size) using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and methanol (eluent B) in the gradient elution mode (10min of total analysis). The method gave satisfactory results in terms of linearity with r(2)(-values)>0.9986 within the established concentration range. The LOD varied from 85ngmL(-1) (ferulic acid) to 0.32μgmL(-1) ((+)-catechin), whereas the LOQ values from 0.028μgmL(-1) (ferulic acid) to 1.08μgmL(-1) ((+)-catechin). Typical recoveries ranged between 81.1 and 99.6% for red wines and between 77.1 and 99.3% for white wines, with relative standard deviations (RSD) no larger than 10%. The extraction yields of the MEPS(C8)/UHPLC-PDA methodology were found between 78.1 (syringic acid) and 99.6% (o-coumaric acid) for red wines and between 76.2 and 99.1% for white wines. The inter-day precision, expressed as the relative standard deviation (RSD%), varied between 0.2% (p-coumaric and o-coumaric acids) and 7.5% (gentisic acid) while the intra-day precision between 0.2% (o-coumaric and cinnamic acids) and 4.7% (gallic acid and (-)-epicatechin). On the basis of analytical validation, it is shown that the MEPS(C8)/UHPLC-PDA methodology proves to be an improved, reliable, and ultra-fast approach for wine bioactive phenolics analysis, because of its capability for determining simultaneously in a single chromatographic run several bioactive metabolites with high sensitivity, selectivity and resolving power within only 10min. Preliminary studies have been carried out on 34 real whole wine samples, in order to assess the performance of the described procedure. The new approach offers decreased sample preparation and analysis time, and moreover is cheaper, more environmentally friendly and easier to perform as compared to traditional methodologies.
Animal Reproduction Science. Jan, 2012 | Pubmed ID: 22305771
The aims were to determine resistance index (RI) and pulsatility index (PI) in the uterine arteries of cyclic and pregnant domestic cats comparing the left and right uterine horns, as well as the majority or minority uterine horns, based on fetus number per horn; to determine the presence or absence of an early diastolic notch (EDN) in the uterine artery of pregnant queens. Ten domestic cats were followed during one cycle and one pregnancy until 63rd days after mating. The estrous cycle length was 16±9.57days. The uterine horn with the highest number of fetuses (majority uterine horn - MUH) presented 2.0±1.0 fetus and the lower (minority uterine horn - miUH) presentes 0.78±0.67 fetus. There were no differences in indexes between uterine arteries during the cycles and pregnancies. The RI and PI of MUH were lower than miUH (P<0.05). Uterine artery of the MUH presented lower indexes than miUH during the acceptance period (P<0.05). On D14 of pregnancy, uterine artery presented reductions in both indexes for the miUH. On D56, the PI was reduced in the miUH. The indexes depended on the week of pregnancy. EDN was present on the uterine arteries of all cats until D35, but disappeared by D49. The blood flow varied according to the category of horn.
Different Prognostic Impact of the Tissue Doppler-derived E/e' Ratio on Mortality in Chagas Cardiomyopathy Patients with Heart Failure
The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Feb, 2012 | Pubmed ID: 22305956
BACKGROUND: Risk assessment of Chagas cardiomyopathy patients is essential for clinical decision making. The ratio of the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/e') is a powerful predictor of adverse outcome in patients with heart failure. However, its prognostic value remains to be established in the setting of Chagas cardiomyopathy. This study investigated the effect of E/e' on mortality according to different degrees of left ventricular (LV) systolic function in patients with Chagas cardiomyopathy. METHODS: The study prospectively enrolled 232 patients (143 men) with Chagas cardiomyopathy (mean age, 48 ± 12 years). End points were death or cardiac transplantation. RESULTS: During a mean follow-up of 3.4 years, 107 patients had an adverse cardiac event, with an overall events rate of 13.2/year. Cox proportional hazards model was used with New York Heart Association functional class, LV ejection fraction, right ventricular function, indexed left atrial volume, E/e' ratio, and the statistical interaction term between E/e' ratio and LV ejection fraction. The effect of E/e' ratio on mortality depended on the degree of LV systolic dysfunction. An increasing E/e' ratio was a strong predictor of outcome in patients with mild to moderate LV dysfunction but was inversely associated with mortality in patients with severe systolic dysfunction. CONCLUSION: This study demonstrated the role of the interaction between LV ejection fraction and E/e' ratio in predicting prognosis in Chagas cardiomyopathy patients. The E/e' ratio had a stronger prognostic value in patients with mild and moderate LV dysfunction and was inversely associated with mortality in patients with advanced systolic heart failure.
The Regulation of Cardiac Activity by Nitric Oxide (NO) in the Vietnamese Stick Insect, Baculum Extradentatum
Cellular Signalling. Jan, 2012 | Pubmed ID: 22306270
This study examines the role of the unconventional gaseous signaling molecule nitric oxide (NO) on the regulation of heart rate in the Vietnamese stick insect, Baculum extradentatum. Using nicotinamide dinucleotide hydrogen phosphate (NADPH)-diaphorase histochemistry, as well as immunohistochemistry and Western blotting with an antibody against NO synthetase (NOS), we identified the presence of NOS in hemocytes present throughout the lumen of the dorsal vessel. We propose that NO is delivered to heart muscle tissue via hemocytes circulating within the hemolymph. In the present study, stimulation of NO levels by the application of the NO donor MAHMA-NONOate and l-arginine led to a dose-dependent decrease in heart rate. Treatment of tissues with the NOS inhibitor, L-NAME, in equimolar concentrations with l-arginine, led to a recovery of heart rate, without modifying heart rate on its own. Finally guanosine 3',5'-cyclic monophosphate (cGMP) analog, 8-bromo-cGMP, elicited similar inhibitory effects on stick insect heart rate as did the guanylate cyclase activator, YC-1, and the phosphodiesterase inhibitor, dipyridamole, indicating that cGMP is most likely the second messenger in the stick insect NO signaling pathway. Contrary to the cardioexcitatory effect of NO on other insect hearts, we have found that NO inhibits stick insect heart rate independently from any nervous system input, in a similar inhibitory fashion as that of vertebrate hearts.
Antigen, Antibody and Immune Complex Detection in Serum Samples from Rats Experimentally Infected with Strongyloides Venezuelensis
Experimental Parasitology. Jan, 2012 | Pubmed ID: 22306281
In order to establish an antigen, antibody and immune complex detection by enzyme-linked immunosorbent assay (ELISA) in serum samples, normal or immunocompromised Wistar rats experimentally infected with Strongyloides venezuelensis were used. The microtitre plates were coated with IgG anti-S. venezuelensis for antigen and immune complex detection and with alkaline parasite extract for antibody detection. Analysis revealed at least 12.5μg/mL of S. venezuelensis specific antigens in serum samples. Assay for antigen detection was not a good approach for evaluating infection in normal or immunocompromised rats. In normal rats IgG specific for S. venezuelensis was preferentially detected during the first 13days post-infection (p.i.) and immune complex detection was significantly reduced in 21 p.i. day. On the other hand, in immunocompromised rats, IgG and immune complex were detected during the entire kinetic (5, 8, 13 and 21 p.i). These results suggest that immune complex screening seems to be an alternative for early strongyloidiasis diagnosis in immunocompromised individuals.
Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Jan, 2012 | Pubmed ID: 22306517
The aim of the present work was to study the protective effects of rosmarinic acid against ethanol-induced DNA damage in mice. The antigenotoxic capacity of rosmarinic acid (100mg/kg) was tested using pre-, co- and post-treatment with ethanol (5g/kg). Peripheral blood (1 and 24h) and brain cells (24h) were evaluated using the comet assay and bone marrow was analyzed using the micronucleus assay (24h). The results were compared to data of TBARS, enzymes with antioxidant activity, and DCFH-DA test. Peripheral blood and brain cells show that mean damage index (DI) and damage frequency (DF) values of ethanol with pre-treatment with rosmarinic acid group were significantly lower than in the ethanol group. In brain cells all different treatments with ethanol and rosmarinic acid showed significant decrease in DI and DF mean values when compared to ethanol group and negative control. No significant differences were observed in micronucleus frequency, activity of antioxidant enzymes and TBARS between groups. The DCFH-DA test show a reduction of 18% of fluorescence intensity when compare with ethanol group. The results show that rosmarinic acid could decrease the levels of DNA damage induced by ethanol, for both tissues and treatment periods.