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Find video protocols related to scientific articles indexed in Pubmed.
Review of toluene action: clinical evidence, animal studies and molecular targets.
J Drug Alcohol Res
PUBLISHED: 11-01-2014
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It has long been known that individuals will engage in voluntary inhalation of volatile solvents for their rewarding effects. However, research into the neurobiology of these agents has lagged behind that of more commonly used drugs of abuse such as psychostimulants, alcohol and nicotine. This imbalance has begun to shift in recent years as the serious effects of abused inhalants, especially among children and adolescents, on brain function and behavior have become appreciated and scientifically documented. In this review, we discuss the physicochemical and pharmacological properties of toluene, a representative member of a large class of organic solvents commonly used as inhalants. This is followed by a brief summary of the clinical and pre-clinical evidence showing that toluene and related solvents produce significant effects on brain structures and processes involved in the rewarding aspects of drugs. This is highlighted by tables highlighting toluene's effect on behaviors (reward, motor effects, learning, etc.) and cellular proteins (e.g. voltage and ligand-gated ion channels) closely associated the actions of abused substances. These sections demonstrate not only the significant progress that has been made in understanding the neurobiological basis for solvent abuse but also reveal the challenges that remain in developing a coherent understanding of this often overlooked class of drugs of abuse.
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PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis.
Scand. J. Immunol.
PUBLISHED: 11-01-2014
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Mycobacterium tuberculosis, the primary causative agent of tuberculosis, infects macrophages and transforms the hostile intracellular environment into a permissive niche. M. tuberculosis infects macrophages using a variety of microbial ligand/cell receptor systems. In this study, binding assays with biotin-labeled mycobacterial cell wall proteins revealed five Concanavalin A-reactive proteins that bind macrophages. Among these proteins we identified PstS-1, a 38-kDa M. tuberculosis mannosylated glycolipoprotein, and characterized it as an adhesin. Inhibition assays with mannan and immunoprecipitation demonstrated that PstS-1 binds the mannose receptor. We purified PstS-1 to 95.9% purity using ion exchange chromatography. The presence of mannose in purified PstS-1 was demonstrated by Concanavalin A interaction, which was abolished in the presence of sodium m-periodate and ?-D-mannosidase. Gas chromatography revealed that purified PstS-1 contained 1% of carbohydrates by weight, which was mainly mannose. Finally, we used fluorescent microbeads coated with purified PstS-1 in phagocytosis assays and discovered that microbead uptake was inhibited by the preincubation of cells with GlcNAc, mannan, and ?-methyl-mannoside. The interaction of PstS-1 coated beads with the mannose receptor was confirmed by confocal co-localization studies that showed high Pearson and Manders co-localization coefficients. Our findings contribute to a better understanding of the strategies M. tuberculosis uses to infect host cells, the critical first step in the pathogenesis of tuberculosis. This article is protected by copyright. All rights reserved.
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IDENTIFICATION OF TARGETS FOR PREVENTION OF PERITONEAL CATHETER TUNNEL AND EXIT-SITE INFECTIONS IN LOW INCIDENCE SETTINGS.
Perit Dial Int
PUBLISHED: 10-09-2014
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? Background: Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections. ? Objective: To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections. ? Method: Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis. ? Main results: The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p= 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p= 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ? 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients. ? Conclusions: Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI.
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Association between exposure to rotating night shift versus day shift using levels of 6-sulfatoxymelatonin and cortisol and other sex hormones in women.
Chronobiol. Int.
PUBLISHED: 09-13-2014
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The present study aims to compare 6-sulfatoxymelatonin (aMT6s) secretion patterns and levels of cortisol and sex hormones (estradiol, progesterone, DHEA, DHEAS, and testosterone) among rotating night-shift workers and day-shift workers. We performed a cross-sectional study in Cantabria (northern Spain) including 136 women (73 day-shift workers and 63 rotating night-shift workers). Blood and urine samples were obtained after two consecutive working days. Differences in means were estimated using ANCOVA, stratified by menopausal status, ovulation phase, and adjusted for season, age, body mass index, consumption of cigarettes in the last 24?h. aMT6s circadian rhythm was analyzed using the cosinor analysis. The present study showed that rotating night-shift workers had lower excretion of aMT6s than day-shift workers (mesor?=?50.26?ng aMT6s/mg creatinine in women with rotating night shift versus 88.79?ng aMT6s/mg creatinine in women with day shift), lower fluctuation (amplitude?=?45.24?ng aMT6s/mg creatinine in rotating night-shift workers versus 79.71?ng aMT6s/mg creatinine in day-shift workers), and a later acrophase (aMT6s peak time: 08:31 in rotating night-shift workers versus 07:13?h in day-shift workers). Additionally, women with rotating night shift had higher estradiol and progesterone levels, compared to day workers, especially in the follicular phase on the menstrual cycle.
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Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis.
Schizophr. Res.
PUBLISHED: 08-20-2014
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This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3 months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2 kg [SD=4.1] versus 4.3 kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.
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Chitosan-based mucoadhesive films containing 5-aminolevulinic acid for buccal cancer's treatment.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 08-12-2014
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Photodynamic therapy (PDT) is a relatively new method to treat various kinds of tumors, including those of the oral cavity. The topical 5-ALA-PDT treatment for tumors of the oral mucosa is preferred, since when administered systemically, there is a general photosensitization drawback in the patient. However, 5-ALA is a hydrophilic molecule and its penetration and retention is limited by topical route, including oral mucosa. We propose a topical delivery system of chitosan-based mucoadhesive film, aiming to promote greater retention of 5-ALA in tissue. The chitosan (CHT) films (4% w/w) were prepared using the solvent evaporation/casting technique. They were tested without 5-ALA resulting in permeability to water vapor (W.V.P=2.15-8.54gmm/(hcm(2)Pa) swelling ?300.0% (±10.5) at 4h or 24 h and in vitro residence time >24h for all tests. CHT films containing 10.0% (w/w) 5-ALA have resulted in average weight of 0.22g and thickness of 0.608mm as suitable characteristics for oral application. In the presence of CHT films both in vitro permeation and retention of 5-ALA (1.0% or 10.0%) were increased. However, 10.0% 5-ALA presented highest values of permeation and retention (?4 and 17 times respectively, compared to propylene glycol vehicle). On the other hand, in vitro mucoadhesion of CHT films was decreased (18.2-fold and 3.1-fold) by 5-ALA addition (1.0% or 10.0% respectively). However, CHT film containing 10.0% of 5-ALA can be a potential delivery system for topical use in the treatment of tumors of the oral cavity using PDT because it favored the retention of 5-ALA in this tissue and has shown convenient mucoadhesion.
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Shigella: A Highly Virulent and Elusive Pathogen.
Curr Trop Med Rep
PUBLISHED: 08-12-2014
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Despite a significant decrease in Shigella-related mortality, shigellosis continues to carry a significant burden of disease worldwide, particularly in Asia and Africa. Shigella is a highly virulent pathogen comprised of four major species with numerous subtypes. Shigella dysenteriae and Shigella flexneri infections are predominant in resource-limited settings. Clinical presentations range from mild watery diarrhea to severe dysentery with systemic complications such as electrolyte imbalance, seizures and hemolytic uremic syndrome. S. dysenteriae subtype 1, the producer of Shiga toxin, causes the most severe illness and highest mortality. Susceptible strains of Shigella may be effectively treated with inexpensive oral antibiotics such as ampicillin or trimethoprim-sulfamethoxazole. Unfortunately, multidrug resistant strains have emerged that have rendered most antibiotics, including fluoroquinolones and extended-spectrum cephalosporins, ineffective. Management and prevention of shigellosis represents a major public health challenge. The development of an effective vaccine is urgently needed to decrease its global impact.
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Chalcones as positive allosteric modulators of ?7 nicotinic acetylcholine receptors: a new target for a privileged structure.
Eur J Med Chem
PUBLISHED: 07-22-2014
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The ?7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of ?7 nicotinic function. The most potent compound (2,4,2',5'-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.
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Symptoms and reason for a medical visit in lung cancer patients.
Acta Med Port
PUBLISHED: 06-30-2014
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Patients with lung cancer usually present with symptoms at the time of diagnosis, but it is common that neither the doctor nor the patient initially associate them with the possibility of a malignant tumour.
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Hypernociceptive responses following the intratibial inoculation of RM1 prostate cancer cells in mice.
Prostate
PUBLISHED: 06-24-2014
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Pain due to bone metastases of prostatic origin is a relevant clinical issue. We study here the nociceptive responses obtained in mice receiving the intratibial inoculation of RM1 prostate cancer cells.
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Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway.
Pflugers Arch.
PUBLISHED: 06-23-2014
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Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLC? signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.
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Self-assembly and antimicrobial activity of long-chain amide-functionalized ionic liquids in aqueous solution.
Colloids Surf B Biointerfaces
PUBLISHED: 06-20-2014
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Surface active amide-functionalized ionic liquids (ILs) consisting of a long alkyl chain (C6C14) connected to a polar head group (methylimidazolium or pyridinium cation) via an amide functional group were synthesized and their thermal stability, micellar properties and antimicrobial activity in aqueous solution investigated. The incorporation of an amide group increased the thermal stability of the functionalized ionic liquids compared to simple alkyl chain substituted ionic liquids. The surface activity and aggregation behaviour in aqueous solution of amide-functionalized ionic liquids were examined by tensiometry, conductivity and spectrofluorimetry. Amide-functionalized ILs displayed surface activity and their critical micelle concentration (cmc) in aqueous media decreased with the elongation of the alkyl side chain as occurs for typical surfactants. Compared to non-functionalized ILs bearing the same alkyl chain, ionic liquids with an amide moiety possess higher surface activity (pC20) and lower cmc values. The introduction of an amide group in the hydrophobic chain close to the polar head enhances adsorption at the air/water interface and micellization which could be attributed to the H-bonding in the headgroup region. The antimicrobial activity was evaluated against a panel of representative Gram-negative and Gram-positive bacteria and fungi. Amide-functionalized ILs with more than eight carbon atoms in the side chain showed broad antimicrobial activity. Antibacterial activities were found to increase with the alkyl chain length being the C12 homologous the most effective antimicrobial agents. The introduction of an amide group enhanced significantly the antifungal activity as compared to non-functionalized ILs.
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Impact of the New American and British Guidelines on the Management and Treatment of Dyslipidemia in a Spanish Working Population.
Rev Esp Cardiol (Engl Ed)
PUBLISHED: 06-16-2014
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The guidelines of the American College of Cardiology/American Heart Association and the British National Institute for Health and Clinical Excellence on the management and treatment of dyslipidemia recommend significant changes, such as the abolition of therapeutic targets and the use of new risk tables. This study aimed to evaluate the impact of the use of these new guidelines compared with the application of European guidelines.
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Prolonged QT interval in ST-elevation myocardial infarction and mortality: new prognostic scale with QT, Killip and age.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 06-13-2014
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To analyze the relation between prolonged QT interval and mortality in patients with ST-elevation myocardial infarction and complementarity with Killip, Thrombolysis in Myocardial Infarction (TIMI) and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scales.
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Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: a systematic review and meta-analysis.
J. Neuroimmunol.
PUBLISHED: 06-10-2014
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We aimed to quantify the association of blood interleukin-6 (IL-6) concentrations with poor outcome after stroke and its added predictive value over clinical information. Meta-analysis of 24 studies confirmed this association with a weighted mean difference of 3.443 (1.592-5.294) pg/mL, despite high heterogeneity and publication bias. Individual participant data including 4112 stroke patients showed standardized IL-6 levels in the 4th quartile were independently associated with poor outcome (OR=2.346 (1.814-3.033), p<0.0001). However, the additional predictive value of IL-6 was moderate (IDI=1.5%, NRI=5.35%). Overall these results indicate an unlikely translation of IL-6 into clinical practice for this purpose.
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Enteroaggregative coli: A Pathogen Bridging the North and South.
Curr Trop Med Rep
PUBLISHED: 06-04-2014
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Enteroaggregative Escherichia coli (EAEC) is a heterogeneous emerging enteric pathogen. Identified during the 1980's when EAEC strains where isolated from cases of acute and persistent diarrhea among infants from developing countries and of traveler's diarrhea. Subsequently, EAEC strains were linked with foodborne outbreaks and diarrhea illness in adults and children from industrialized countries, HIV-infected subjects and stunting of malnourished poor children. Nowadays, EAEC is increasingly recognized as a major cause of acute diarrhea in children recurring hospitalization and of traveler's diarrhea worldwide. EAEC strains defining phenotype is the aggregative adherence (AA) pattern on epithelial cells. AggR a transcriptional regulator of several EAEC virulence genes has been a key factor in both understanding EAEC pathogenesis and defining typical EAEC (tEAEC) strains. EAEC virulence genes distribution among these strains is highly variable. Present challenges are the identification of key virulence genes and how they coordinately function in the setting of enteric disease.
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Home Ventilation Therapy in Obstructive Sleep Apnea-Hypopnea Syndrome.
Arch. Bronconeumol.
PUBLISHED: 06-03-2014
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Obstructive sleep apnea-hypopnea is a highly prevalent disease that is often underdiagnosed at present. It has a significant economic and social welfare impact, accounting for a large part of the resources assigned to home respiratory therapies. As part of the 2014 SEPAR Year of the Chronic Patient and Domiciliary Respiratory Care sponsored by the Spanish Society of Pulmonology and Thoracic Surgery, this article reviews the most recent publications on the indications and controversial issues in the treatment of sleep apnea, the latest evidence for indication of various positive pressure devices, and adjustment modes, ranging from the use of empirical formulae or mathematical estimations to modern auto-CPAP equipment, while not forgetting the gold standard of manual titration. Emphasis is placed on the need for monitoring required by patients to ensure treatment adherence and compliance. Finally, other therapies that are not the object of this article are briefly reviewed.
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Study of the effectiveness of first-line treatment in renal cell carcinoma.
Mol Clin Oncol
PUBLISHED: 05-13-2014
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The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P<0.001) were found between the groups. Therefore, it was concluded that the effectiveness of the treatments was reduced compared to previous studies and differences were found in the PP group when classified by first-line drug and histology. Additionally, the influence of prognostic factors on OS and the value of stratifying patients using these factors have been confirmed.
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De novo designed library of linear helical peptides: an exploratory tool in the discovery of protein-protein interaction modulators.
ACS Comb Sci
PUBLISHED: 04-22-2014
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Protein-protein interactions (PPIs) have emerged as important targets for pharmaceutical intervention because of their essential role in numerous physiological and pathological processes, but screening efforts using small-molecules have led to very low hit rates. Linear peptides could represent a quick and effective approach to discover initial PPI hits, particularly if they have inherent ability to adopt specific peptide secondary structures. Here, we address this hypothesis through a linear helical peptide library, composed of four sublibraries, which was designed by theoretical predictions of helicity (Agadir software). The 13-mer peptides of this collection fixes either a combination of three aromatic or two aromatic and one aliphatic residues on one face of the helix (Ac-SSEEX(5)ARNX(9)AAX(12)N-NH2), since these are structural features quite common at PPIs interfaces. The 81 designed peptides were conveniently synthesized by parallel solid-phase methodologies, and the tendency of some representative library components to adopt the intended secondary structure was corroborated through CD and NMR experiments. As proof of concept in the search for PPI modulators, the usefulness of this library was verified on the widely studied p53-MDM2 interaction and on the communication between VEGF and its receptor Flt-1, two PPIs for which a hydrophobic ?-helix is essential for the interaction. We have demonstrated here that, in both cases, selected peptides from the library, containing the right hydrophobic sequence of the hot-spot in one of the protein partners, are able to interact with the complementary protein. Moreover, we have discover some new, quite potent inhibitors of the VEGF-Flt-1 interaction, just by replacing one of the aromatic residues of the initial F(5)Y(9)Y(12) peptide by W, in agreement with previous results on related antiangiogenic peptides. Finally, the HTS evaluation of the full collection on thermoTRPs has led to a few antagonists of TRPV1 and TRPA1 channels, which open new avenues on the way to innovative modulators of these channels.
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Promoter polymorphisms of ST3GAL4 and ST6GAL1 genes and associations with risk of premalignant and malignant lesions of the cervix.
Asian Pac. J. Cancer Prev.
PUBLISHED: 03-11-2014
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Sialyltransferase gene expression is altered in several cancers, including examples in the cervix. Transcriptional regulation of the responsible genes depends on different promoters. We aimed to determine the association of single-nucleotide polymorphisms in the B3 promoter of the ST3GAL4 gene and the P1 promoter of the ST6GAL1 gene with cervical premalignant lesions or cervical cancer. A blood sample and/or cervical scrapes were obtained from 104 women with normal cytology, 154 with premalignant lesions and 100 with cervical cancer. We also included 119 blood samples of random donors. The polymorphisms were identified by sequencing from PCR products. For the B3 promoter, a fragment of 506 bp (from nucleotide -408 to +98) was analyzed, and for the P1 promoter a 490 bp (-326 to +164) fragment. The polymorphism analysis showed that at SNP rs10893506, genotypes CC and CT of the ST3GAL4 B3 promoter were associated with the presence of premalignant lesions (OR=2.89; 95%CI 1.72-4.85) and cervical cancer (OR=2.23; 95%CI 1.27-3.91). We detected only one allele of each polymorphism in the ST6GAL1 P1 promoter. We did not detect any genetic variability in the P1 promoter region in our study population. Our results suggest that the rs10893506 polymorphism -22C/T may increase susceptibility to premalignant and malignant lesions of the cervix.
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A rosemary extract enriched in carnosic acid improves circulating adipocytokines and modulates key metabolic sensors in lean Zucker rats: Critical and contrasting differences in the obese genotype.
Mol Nutr Food Res
PUBLISHED: 02-20-2014
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Carnosic acid (CA) and rosemary extracts (REs) have antiobesity effects but the mechanisms are not understood. We investigated some of the potential mechanisms contributing to the metabolic effects of an RE enriched in CA.
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Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-19-2014
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To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT).
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Role of beta-defensin 2 and interleukin-4 receptor as stroke outcome biomarkers.
J. Neurochem.
PUBLISHED: 02-11-2014
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Acute ischemic stroke is a complex disease with huge interindividual evolution variability that makes challenging the prediction of an adverse outcome. Our aim was to study the association of bloodstream signatures to early neurological outcome after stroke, by combining a subpooling of samples strategy with protein array discovery approach. Plasma samples from 36 acute stroke patients (< 4.5 h from onset) were equally pooled within outcome groups: worsening, stability, and improvement (n = 3 pools of four patients each, for each outcome group). These nine pools were screened using a 177 antibodies library, and 35 proteins were found altered regarding outcome classification (p < 0.1). Processes of inflammation, immune response, coagulation, and apoptosis were regulated by these proteins. Ten representative candidates, mainly cytokines and chemokines, were assayed for replication in individual baseline plasma samples from 80 new stroke patients: ?-defensin2, MIP-3b, plasminogen activator inhibitor 1 active, ?-cell-attracting chemokine 1, Exodus-2, interleukin-4 receptor (IL-4R), IL-12p40, leukemia inhibitor factor, MIP-1b, and tumor necrosis factor-related weak inducer of apoptosis. Multivariate logistic regression analysis showed ?-defensin 2 (ORadj 4.87 [1.13-20.91] p = 0.033) and IL-4R (ORadj 3.52 [1.03-12.08] p = 0.045) as independent predictors of worsening at 24 h after adjustment by clinical variables. Both biomarkers improve the prediction by 19% as compared to clinical information, suggesting a potential role for risk stratification in acute thrombolyzed stroke patients. Early neurological deterioration after stroke is not easily predictable. The use of blood biomarkers might help in decision-making processes regarding this complication. By combining a sub-pooling of samples strategy with protein array discovery approach, we have found two new biomarkers: beta-defensin-2 and interleukin-4 receptor. Both biomarkers improve the prediction of poor-outcome over clinical variables in the acute phase of stroke.
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Exploring the Phe-Gly dipeptide-derived piperazinone scaffold in the search for antagonists of the thrombin receptor PAR1.
Molecules
PUBLISHED: 02-04-2014
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A series of Phe-Gly dipeptide-derived piperazinones containing an aromatic urea moiety and a basic amino acid has been synthesized and evaluated as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cells. The synthetic strategy involves coupling of a protected basic amino acid benzyl amide to 1,2- and 1,2,4-substituted-piperazinone derivatives, through a carbonylmethyl group at the N1-position, followed by formation of an aromatic urea at the exocyclic moiety linked at the C2 position of the piperazine ring and removal of protecting groups. None of the compounds showed activity in the biological evaluation.
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Content and evolution of potential furfural compounds in commercial milk-based infant formula powder after opening the packet.
Food Chem
PUBLISHED: 01-23-2014
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Potential furfural compounds were examined by RP-HPLC-DAD in 20 commercial milk-based powdered infant formula (IF) brands from local markets from Paris, France; DF, Mexico; Copenhagen, Denmark; England, UK; and Barcelona, Spain. We traced the evolution of these compounds after the packets had been opened at 0, 30 and 70 days of storage at room temperature (?25 °C; minimum 23 °C and maximum 25.5 °C). All formula brands were analysed during the first 3-5 months of their shelf life. The mean values of all IFs for potential 5-hydroxymethyl-2-furaldehyde (HMF)+2-furaldehyde (F) were 1115.2 ?g/100 g (just opened), 1157.6 ?g/100 g (30 days) and 1344.5 ?g/100 g of product (70 days). In general, slight increases of potential furfural contents were observed in most of the studied IFs, which suggests that the Maillard reaction increases after opening the packets. The main furfural compound found was HMF, as expected. The range of potential HMF consumed for an infant about 6 months old feeding only on formula was estimated between 0.63 mg and 3.25 mg per day.
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Gender and hemispheric differences in temporal lobe epilepsy: a VBM study.
Seizure
PUBLISHED: 01-22-2014
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Gender differences are recognized in the functional and anatomical organization of the human brain. Differences between genders are probably expressed early in life, when differential rates of cerebral maturation occur. Sexual dimorphism has been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). Several voxel-based morphometry (VBM) studies have shown that TLE-MTS extends beyond mesial temporal structures, and that there are differences in the extent of anatomical damage between hemispheres, although none have approached gender differences. Our aim was to investigate gender differences and anatomical abnormalities in TLE-MTS.
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Dosimetric characteristics of a new unit for electronic skin brachytherapy.
J Contemp Brachytherapy
PUBLISHED: 01-15-2014
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Brachytherapy with radioactive high dose rate (HDR) (192)Ir source is applied to small skin cancer lesions, using surface applicators, i.e. Leipzig or Valencia type. New developments in the field of radiotherapy for skin cancer include electronic brachytherapy. This technique involves the placement of an HDR X-ray source close to the skin, therefore combining the benefits of brachytherapy with the reduced shielding requirements and targeted energy of low energy X-rays. Recently, the Esteya(®) Electronic Brachytherapy System (Esteya EBS, Elekta AB-Nucletron, Stockholm, Sweden) has been developed specifically for HDR brachytherapy treatment of surface lesions. The system provides radionuclide free HDR brachytherapy by means of a small 69.5 kV X-ray source. The purpose of this study is to obtain the dosimetric characterization required for clinical implementation, providing the detailed methodology to perform the commissioning.
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An extension of the Theory of Planned Behavior to predict willingness to pay for the conservation of an urban park.
J. Environ. Manage.
PUBLISHED: 01-11-2014
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This paper relates the concept of moral obligation and the components of the Theory of Planned Behavior to determine their influence on the willingness to pay of visitors for park conservation. The sample consists of 190 visitors to an urban Spanish park. The mean willingness to pay estimated was 12.67€ per year. The results also indicated that moral norm was the major factor in predicting behavioral intention, followed by attitudes. The new relations established between the components of the Theory of Planned Behavior show that social norms significantly determine the attitudes, moral norms and perceived behavioral control of individuals. The proportion of explained variance shows that the inclusion of moral norms improves the explanatory power of the original model of the Theory of Planned Behavior (32-40%). Community-based social marketing and local campaigns are the main strategies that should be followed by land managers with the objective of promoting responsible, pro-environmental attitudes as well as a greater willingness to pay for this type of goods.
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Micellization of sodium laurylethoxysulfate (SLES) and short chain imidazolium ionic liquids in aqueous solution.
J Colloid Interface Sci
PUBLISHED: 01-10-2014
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In the present study the interactions between an anionic surfactant sodium laurylethoxysulfate (SLES) and three short chain imidazolium (1-butyl-3-methylimidazolium) based ionic liquids (bmim-octyl SO4, bmim-methyl SO4 and bmim-BF4) in aqueous solution have been investigated. Generally when a surfactant is dissolved in a hydrophilic ionic liquid aqueous solution the critical micelle concentration (cmc) obtained is attributed to the surfactant because the ionic liquid (IL) is considered to be only a cosolvent. However, some short hydrophilic ionic liquids posses surface activity in aqueous solution and behave like a surfactant. In that case mixed aggregates between surfactant and ionic liquid can be formed. The three SLES/IL systems here studied have been treated as typical binary surfactant mixtures in aqueous solution. Surface tension measurements have revealed that mixed aggregates and monolayers of surfactant and ionic liquid instead of single surfactant are responsible for the surface active properties of these aqueous solutions. From the Regular Solution Theory, negative interaction parameters (?) for mixed aggregates and monolayers have been found for all SLES/IL mole ratios indicating synergism between the anionic surfactant and the ionic liquids.
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Testosterone response to competition in males is unrelated to opponent familiarity or threat appraisal.
Front Psychol
PUBLISHED: 01-01-2014
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It has been proposed in the literature that the testosterone (T) response to competition in humans may be modulated by cognitive variables. In a previous experiment with a female sample we have reported that opponent familiarity and threat appraisal moderated the T response to competition in women. With this experiment we aim to investigate if these variables have the same impact on males T response to competition, extending the previous findings in our lab. Forty male participants (20 dyads) were recruited to engage in a same sex, face to face competition using the Number Tracking Test as a competitive task. Levels of T, cortisol (C) and dehydroepiandrosterone (DHEA) were measured before and 20 min after the competition. Results show that losers report higher levels of threat than winners and increased their T levels after the competition, however this T change was not predicted by opponent familiarity or threat appraisal. No variation was detected for C and DHEA levels. These findings suggest that there could be sex differences for the moderators/mediators of the T response to competition in humans.
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Challenge and threat motivation: effects on superficial and elaborative information processing.
Front Psychol
PUBLISHED: 01-01-2014
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This paper integrates the motivational states of challenge and threat within a dual processing perspective. Previous research has demonstrated that individuals experience a challenge state when individuals have sufficient resources to cope with the demands of a task (Blascovich et al., 1993). Because the experience of resource availability has been shown to be associated with superficial processing (Garcia-Marques and Mackie, 2007), we tested the hypothesis that challenge is associated with superficial processing in two persuasion experiments. Experiment 1 revealed that inducing attitudes of participants in a challenge state was not sensitive to the quality of arguments presented. Experiment 2 demonstrated that the effect occurs even when task engagement, manipulated by the presence (vs. the absence) of a task observer (Blascovich et al., 1993), is high. The implications of these results for the biopsychosocial model model and the cognitive and motivational literature are discussed.
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Magnetic biocatalysts and their uses to obtain biodiesel and biosurfactants.
Front Chem
PUBLISHED: 01-01-2014
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Nanobiocatalysis, as the synergistic combination of nanotechnology and biocatalysis, is rapidly emerging as a new frontier of biotechnology. The use of immobilized enzymes in industrial applications often presents advantages over their soluble counterparts, mainly in view of stability, reusability and simpler operational processing. Because of their singular properties, such as biocompatibility, large and modifiable surface and easy recovery, iron oxide magnetic nanoparticles (MNPs) are attractive super-paramagnetic materials that serve as a support for enzyme immobilization and facilitate separations by applying an external magnetic field. Cross-linked enzyme aggregates (CLEAs) have several benefits in the context of industrial applications since they can be cheaply and easily prepared from unpurified enzyme extracts and show improved storage and operational stability against denaturation by heat and organic solvents. In this work, by using the aforementioned advantages of MNPs of magnetite and CLEAs, we prepared two robust magnetically-separable types of nanobiocatalysts by binding either soluble enzyme onto the surface of MNPs functionalized with amino groups or by cross-linking aggregates of enzyme among them and to MNPs to obtain magnetic CLEAs. For this purpose the lipase B of Candida antarctica (CALB) was used. The hydrolytic and biosynthetic activities of the resulting magnetic nanobiocatalysts were assessed in aqueous and organic media. Thus, the hydrolysis of triglycerides and the transesterification reactions to synthesize biodiesel and biosurfactants were studied using magnetic CLEAs of CALB. The efficiency and easy performance of this magnetic biocatalysis validates this proof of concept and sets the basis for the application of magnetic CLEAs at industrial scale.
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A rosemary extract rich in carnosic acid selectively modulates caecum microbiota and inhibits ?-glucosidase activity, altering fiber and short chain fatty acids fecal excretion in lean and obese female rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity.
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Fluorescent Molecular Peroxidation Products: A Prognostic Biomarker of Early Neurologic Deterioration After Thrombolysis.
Stroke
PUBLISHED: 12-12-2013
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Fluorescent molecular peroxidation products (FMPPs) are considered potential markers of molecular oxidative damage and may provoke increased permeability and disruption of the blood-brain barrier. This study aimed to determine the value of FMPPs as a biomarker to predict neurological worsening related to early hemorrhagic transformation.
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B-type natriuretic peptides and mortality after stroke: A systematic review and meta-analysis.
Neurology
PUBLISHED: 11-01-2013
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To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information.
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Down-regulation of CaV1.2 channels during hypertension: how fewer CaV1.2 channels allow more Ca2+ into hypertensive arterial smooth muscle.
J. Physiol. (Lond.)
PUBLISHED: 10-28-2013
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Abstract? Hypertension is a clinical syndrome characterized by increased arterial tone. Although the mechanisms are varied, the generally accepted view is that increased CaV1.2 channel function is a common feature of this pathological condition. Here, we investigated the mechanisms underlying vascular dysfunction in a mouse model of genetic hypertension. Contrary to expectation, we found that whole-cell CaV1.2 currents (ICa) were lower in hypertensive (BPH line) than normotensive (BPN line) myocytes. However, local CaV1.2 sparklet activity was higher in BPH cells, suggesting that the relatively low ICa in these cells was produced by a few hyperactive CaV1.2 channels. Furthermore, our data suggest that while the lower expression of the pore-forming ?1c subunit of CaV1.2 currents underlies the lower ICa in BPH myocytes, the increased sparklet activity was due to a different composition in the auxiliary subunits of the CaV1.2 complexes. ICa currents in BPN cells were produced by channels composed of ?1c/?2?/?3 subunits, while in BPH myocytes currents were probably generated by the opening of channels formed by ?1c/?2?/?2 subunits. In addition, Ca(2+) sparks evoked large conductance, Ca(2+)-activated K(+) (BK) currents of lower magnitude in BPH than in BPN myocytes, because BK channels were less sensitive to Ca(2+). Our data are consistent with a model in which a decrease in the global number of CaV1.2 currents coexist with the existence of a subpopulation of highly active channels that dominate the resting Ca(2+) influx. The decrease in BK channel activity makes the hyperpolarizing brake ineffective and leads BPH myocytes to a more contracted resting state.
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Selection of recombinant antibodies by phage display technology and application for detection of allergenic Brazil nut (Bertholletia excelsa) in processed foods.
J. Agric. Food Chem.
PUBLISHED: 10-18-2013
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Current immunological methods for detection of Brazil nut allergens in foods are based on polyclonal antibodies raised in animals. Phage display technology allows the procurement of high-affinity antibodies avoiding animal immunization steps and therefore attaining the principle of replacement supported by animal welfare guidelines. In this study, we screened Tomlinson I and J libraries for specific binders against Brazil nut by employing a Brazil nut protein extract and a purified Brazil nut 2S globulin, and we successfully isolated a phage single chain variable fragment (named BE95) that specifically recognizes Brazil nut proteins. The selected phage scFv was further used as affinity probe to develop an indirect phage-ELISA for detection of Brazil nut in experimental binary mixtures and in commercial food products, with a limit of detection of 5 mg g(-1). This study describes for the first time the isolation of recombinant antibody fragments specific for an allergenic tree nut protein from a naïve library and paves the way to develop new immunoassays for food analysis based on probes that can be produced in vitro when required and do not rely on animal immunization.
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Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors.
Int. J. Neuropsychopharmacol.
PUBLISHED: 10-08-2013
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Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.
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Persistent bloody diarrhoea without fever associated with diffusely adherent Escherichia coli in a young child.
J. Med. Microbiol.
PUBLISHED: 09-11-2013
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Diffusely adherent Escherichia coli (DAEC) is thought to cause diarrhoea in children, and so too are other diarrhoeagenic E. coli (DEC); however, the evidence base is inconclusive. DEC pathotypes are differentiated on the basis of their pathogenic features, and thus cannot be quickly identified on selective culture media. Molecular techniques, not readily available in most clinical laboratories, are required to differentiate DEC strains from non-pathogenic E. coli in the stool flora. We report a case of persistent bloody diarrhoea, without fever, in a previously healthy 21-month infant from whom we isolated five DAEC strains. The childs stools movements were loose, with gross blood and mucus; fresh mount analysis revealed numerous faecal leukocytes and erythrocytes. Response to antimicrobial treatment with trimethoprim-sulfamethoxazole was poor despite susceptibility in vitro. Although the patient improved with azithromycin, blood was present in the patients stools for over 30 days. The severe diarrhoea in this patient might be explained by the fact that these DAEC isolates harboured a siderophore receptor, which allows the bacteria to use iron derived from haem compounds that promote its multiplication. The isolates also induced in vitro secretion of several immunomodulatory cytokines that may account for the patients loose stools and faecal leukocytes. DAEC may play a greater role than suspected in afebrile children with bloody diarrhoea.
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From brain to blood: New biomarkers for ischemic stroke prognosis.
J Proteomics
PUBLISHED: 08-12-2013
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Despite being ischemic stroke a leading cause of death and functional disability, there are no other accurate tools to predict outcome of patients beyond clinical variables such as age and stroke severity. In this scenario, defining protein changes associated with acute ischemic brain damage might help to identify new biomarker candidates for stroke prognosis. By means of mass spectrometry-based proteomics, we identified 51 proteins which levels were altered in the infarcted area of the human brain after stroke. Among 8 selected protein candidates, circulating levels of gelsolin, dihydropyrimidinase-related protein 2 and cystatin A were independent predictors of poor outcome. Logistic regression models including these innovative biomarkers significantly improved the predictive value with respect to the only use of clinical variables in both discrimination and reclassification analyses. Our results indicate that early blood determination of these three biomarkers might predict outcome of patients and might help in decision-making processes related to ischemic stroke management.
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A proteomic and metabolomic approach for understanding the role of the flor yeast mitochondria in the velum formation.
Int. J. Food Microbiol.
PUBLISHED: 08-07-2013
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Saccharomyces cerevisiae "flor" yeast shows a strong tolerance to high ethanol concentrations and develops a velum (biofilm) on the wine surface after the alcoholic fermentation of grape must. This velum remains along several years during the so called "biological aging" process in the elaboration of some special wines carried out in specific regions around the world and it contributes to the typical organoleptic characteristics of these wines. In order to grow in this condition, flor yeast has to elaborate a response where the mitochondrial function is essential. The objective of this study is to elucidate the role of the mitochondria in the response of a flor yeast, S. cerevisiae G1, growing in a controlled velum formation condition. For this purpose, proteome and metabolome were characterized by comparing data with those from an initial fermentative condition used as reference. The obtained proteomic profiles show more mitochondrial proteins related with the ethanol resistance (13), cell respiration (18), mitochondrial genome maintenance (13), and apoptosis (2) detected under the velum formation condition. Also, the finger-printing obtained by means of the exo-metabolites directly related with the quality of fermented beverages and quantified in the velum condition shows important differences from those obtained in the reference condition.
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Occurrence of potentially pathogenic nontuberculous mycobacteria in Mexican household potable water: a pilot study.
BMC Res Notes
PUBLISHED: 07-20-2013
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Nontuberculous mycobacteria (NTM) are environmental opportunistic pathogens found in natural and human-engineered waters, including drinking water distribution systems and household plumbing. This pilot study examined the frequency of occurrence of NTM in household potable water samples in Mexico City. Potable water samples were collected from the "main house faucet" and kitchen faucet. The presence of aerobic-mesophilic bacteria (AMB), total coliforms (TC), fecal coliforms (FC) and NTM species were determined. Mycobacteria species were identified by PCR restriction enzyme pattern analysis (PRA) of the 65-kDa heat shock protein gene (hsp65) and sequencing of the hypervariable region 2 (V2) of the 16S rRNA gene and of the rpoB gene.
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Avian-specific real-time PCR assay for authenticity control in farm animal feeds and pet foods.
Food Chem
PUBLISHED: 07-07-2013
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A highly sensitive TaqMan real-time PCR assay targeting the mitochondrial 12S rRNA gene was developed for detection of an avian-specific DNA fragment (68bp) in farm animal and pet feeds. The specificity of the assay was verified against a wide representation of animal and plant species. Applicability assessment of the avian real-time PCR was conducted through representative analysis of two types of compound feeds: industrial farm animal feeds (n=60) subjected to extreme temperatures, and commercial dog and cat feeds (n=210). Results obtained demonstrated the suitability of the real-time PCR assay to detect the presence of low percentages of highly processed avian material in the feed samples analysed. Although quantification results were well reproducible under the experimental conditions tested, an accurate estimation of the target content in feeds is impossible in practice. Nevertheless, the method may be useful as an alternative tool for traceability purposes within the framework of feed control.
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Genus-specific PCR assay for screening Arcobacter spp. in chicken meat.
J. Sci. Food Agric.
PUBLISHED: 07-05-2013
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The number of emerging pathogenic species described within the genus Arcobacter has increased rapidly during the last few years. In this work a genus-specific polymerase chain reaction (PCR) assay was developed for detection of the species of Arcobacter most commonly associated with foods. The assay uses primers designed to amplify an 85 bp DNA fragment on the 16S rRNA gene and was applied to the detection of Arcobacter spp. in retail chicken meat.
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CORRELATION BETWEEN GLYCEMIC CONTROL AND THE INCIDENCE OF PERITONEAL AND CATHETER TUNNEL AND EXIT-SITE INFECTIONS IN DIABETIC PATIENTS UNDERGOING PERITONEAL DIALYSIS.
Perit Dial Int
PUBLISHED: 07-01-2013
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Diabetes mellitus, especially if complicated by poor glycemic control, portends an increased risk of infection. The significance of this association in the case of diabetic patients undergoing peritoneal dialysis (PD) has not been assessed.
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High resolution TaqMan real-time PCR approach to detect hazelnut DNA encoding for ITS rDNA in foods.
Food Chem
PUBLISHED: 05-02-2013
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A broad range of foods have been described as causing allergies, but the majority of allergic reactions can be ascribed to a limited number of food components. Recent extensive surveys showed how tree nuts, particularly hazelnut (Corylus avellana L.) seeds, rank amongst the most important sources of food allergy. In order to protect the allergic consumer, efficient and reliable methods are required for the detection of allergenic ingredients. For this purpose, we have developed a real-time polymerase chain reaction (PCR) for detection of hazelnut in commercial food products. In this way a specific hazelnut primer pair based on the ITS marker (70 bp) and a nuclease (TaqMan) probe labelled with FAM and BHQ were designed. Sensibility of real-time PCR was determined by analysis of raw and heat treated hazelnut-wheat flour mixtures with a range of detection of 0.1-100,000 ppm. Practical applicability of the real-time PCR assay developed for determining hazelnut in different food matrices was investigated by analyzing 179 commercial foodstuffs comprising snacks, biscuits, chocolates, bonbons, creams, nut bars, ice creams, precooked meals, breads, beverages, yogurts, cereals, meat products, rice cake and nougat. From the total of samples analyzed, 40 commercial food products that didnt declare hazelnut nor traces on the label were found to contain hazelnut. The real-time PCR method proposed herein due to its high sensitivity facilitates the detection of hazelnut traces in commercial food products and can also be useful for monitoring the effectiveness of cleaning processes and as consequence, can help to prevent the food allergic consumer from unintentional ingestion of hidden allergens.
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Nutraceuticals for older people: facts, fictions and gaps in knowledge.
Maturitas
PUBLISHED: 05-02-2013
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In the last decades nutraceuticals have entered the health market as an easy and attractive means of preventing diseases. These products are of interest for an increasingly health-concerned society and may be especially relevant for preventing or delaying a number of age-related diseases, i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Nutraceuticals are marketed in a variety of forms, composition and potential applications which have made their definition ambiguous and their use uncontrolled and poorly funded. Although epidemiological, animal and in vitro studies have given evidence of the potential benefits of some of these nutraceuticals or of their components, definitive proof of their effects in appropriate human clinical trials is still lacking in most cases, more critically among people above 65 years of age. We cover the well-established nutraceuticals (polyvitamins, omega-3 fatty acids, etc.) and will focus on many other novel commercial nutraceuticals where the scientific evidence is more limited (food extracts, polyphenols, carotenoids, etc.). Solid scientific evidence has been reported only for a few nutraceuticals, which have some health claims approved by the European Food Safety Authority (EFSA). Further well-designed trials are needed to improve the current knowledge on the health benefits of nutraceuticals in the elderly. Overall, there are some facts, a lot of fiction and many gaps in the knowledge of nutraceutical benefits.
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Highly functionalized 2-oxopiperazine-based peptidomimetics: An approach to PAR1 antagonists.
Eur J Med Chem
PUBLISHED: 04-08-2013
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A series of pseudodipeptide-based chiral 1,3,4,5-tetrasubstituted-2-oxopiperazines has been designed and synthesized as potential PAR1 antagonists. These highly functionalized piperazines were synthesized from aromatic and basic amino acid derived ?[CH(CN)NH]pseudodipeptides through a four step pathway that involves reduction of the cyano group to build the 2-oxopiperazine ring, followed by selective functionalization at the N4-, N1-positions, and at the exocyclic moiety at position C5. This regioselective functionalization required the fine tuning of reaction conditions. All new compounds were screened as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cell lines. Some of the compounds displayed moderate PAR1 antagonist activity, while, others were cytotoxic at ?M concentration. No correlation was observed between both types of activities.
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Hemolytic anemia after mitral valve repair: a case report.
BMC Res Notes
PUBLISHED: 03-25-2013
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Hemolytic anemia after mitral valve repair is still an underestimated complication because it is a rare condition and there are few described case reports in the literature. The mechanism responsible for hemolysis most commonly involves a regurgitant jet and it appears to be independent of its severity as assessed by echocardiography. Patients may experience severe symptoms with only moderate regurgitant jets.
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Sweet wine production by two osmotolerant Saccharomyces cerevisiae strains.
J. Food Sci.
PUBLISHED: 03-01-2013
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The use of Saccharomyces cerevisiae to produce sweet wine is difficult because yeast is affected by a hyperosmotic stress due to the high sugar concentrations in the fermenting must. One possible alternative could be the coimmobilization of the osmotolerant yeast strains S. cerevisiae X4 and X5 on Penicillium chrysogenum strain H3 (GRAS) for the partial fermentation of raisin musts. This immobilized has been, namely, as yeast biocapsules. Traditional sweet wine (that is, without fermentation of the must) and must partially fermented by free yeast cells were also used for comparison. Partially fermented sweet wines showed higher concentration of the volatile compounds than traditionally produced wines. The wines obtained by immobilized yeast cells reached minor concentrations of major alcohols than wines by free cells. The consumption of specific nitrogen compounds was dependent on yeast strain and the cellular immobilization. A principal component analysis shows that the compounds related to the response to osmotic stress (glycerol, acetaldehyde, acetoin, and butanediol) clearly differentiate the wines obtained with free yeasts but not the wines obtained with immobilized yeasts.
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Immunological biomarkers improve the accuracy of clinical risk models of infection in the acute phase of ischemic stroke.
Cerebrovasc. Dis.
PUBLISHED: 02-28-2013
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Infection is an independent risk factor for adverse outcome in stroke patients. The risk of developing an infection in this setting is partly related to a stroke-induced immunodepression, in which a shift to a predominant Th2 (immunosuppressive) phenotype has been postulated to play a major role. Our aim was to study whether clinical variables or changes in plasma cytokine expression can predict poststroke infections.
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One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
Pharmacol. Res.
PUBLISHED: 02-20-2013
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Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8 mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1? and TNF-? was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.
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Aggregation behavior and antimicrobial activity of ester-functionalized imidazolium- and pyridinium-based ionic liquids in aqueous solution.
Langmuir
PUBLISHED: 02-11-2013
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Two series of long chain imidazolium- and pyridinium-based ionic liquids containing an ester functional group in the alkyl side chain, 3-methyl-1-alkyloxycarbonylmethylimidazolium bromides (C(n)EMeImBr) and 1-alkyloxycarbonylmethylpyridinium bromides (C(n)EPyrBr), were synthesized and their thermal stability, aggregation behavior in aqueous medium, and antimicrobial activity investigated. The introduction of an ester group decreased the thermal stability of the functionalized ILs compared to simple alkyl chain containing ILs (1-alkyl-3-methylimidazolium bromides and 1-alkylpyridinium bromides). Tensiometry, conductimetry, and spectrofluorimetry were applied to study the self-aggregation of the amphiphilic ILs in aqueous solution. The ILs investigated displayed surface activity and the characteristic chain length dependence of the micellization process of surfactants. As compared to simple alkyl chain containing ILs bearing the same hydrocarbon chain, ester-functionalized ILs possess higher adsorption efficiency (pC(20)) and significantly lower critical micelle concentration (cmc) and surface tension at the cmc (?(cmc)), indicating that the incorporation of an ester group promotes adsorption at the air/water interface and micelle formation. The antimicrobial activity was evaluated against Gram-negative and Gram-positive bacteria and fungi. ILs containing more than eight carbon atoms in the alkyl chain showed antimicrobial activity. Their efficiency as antimicrobial agents increased with the hydrophobicity of the amphiphilic cation being the C(12) homologous the most active compounds. The incorporation of an ester group particularly increased the biological activity against fungi.
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Prognostic value of plasma chitotriosidase activity in acute stroke patients.
Int J Stroke
PUBLISHED: 02-05-2013
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Chitotriosidase, a component of innate immunity, constitutes a sensitive parameter of macrophage activation and its elevated plasma activity reflects an inflammatory response. Given the deleterious effects of inflammation in brain ischemia, we aimed to assess the prognostic value of chitotriosidase activity in acute stroke patients.
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Double treatment with paricalcitol-associated calcifediol and cardiovascular risk biomarkers in haemodialysis.
Nefrologia
PUBLISHED: 02-01-2013
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The deficit of 25-hydroxyvitamin D (25OHD) associated with secondary hyperparathyroidism (SHPT) is a frequent finding in chronic kidney disease (CKD) patients on haemodialysis (HD). These events are associated with increased morbidity and mortality rates of cardiovascular (CV) origin. Adequate 25OHD serum levels as well as the use of selective vitamin D receptor activators (VDRA) have been shown to have beneficial and independent effects on bone mineral metabolism and cardiovascular risk. Currently, there is still controversy regarding the type of supplementation needed by CKD patients on HD.
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Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence.
Curr. Pharm. Des.
PUBLISHED: 01-30-2013
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Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of foodstuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol- based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of potential benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called Resveratrol Paradox, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently available evidence regarding resveratrols effects on humans obtained from randomized clinical trials. In addition, we will provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug.
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Bioavailability of the major bioactive diterpenoids in a rosemary extract: metabolic profile in the intestine, liver, plasma, and brain of Zucker rats.
Mol Nutr Food Res
PUBLISHED: 01-18-2013
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Carnosic acid (CA) and derived diterpenes abundant in rosemary extracts (REs) exert anti-obesity effects. The aim of this study was to investigate the bioavailability of these compounds in a rat model of obesity.
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Solvent-free synthesis of ?-amino nitrile-derived ureas.
Org. Lett.
PUBLISHED: 01-15-2013
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An efficient and environmentally friendly methodology for the solvent-free synthesis of ?-amino nitrile derived ureas from ?-amino acid based amino nitriles has been developed. At room temperature no epimerization was observed in the resulting ureas, but under microwave heating, epimerization occurred at the chiral center bearing the cyano group.
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Highly functionalized 1,2-diamino compounds through reductive amination of amino acid-derived ?-keto esters.
PLoS ONE
PUBLISHED: 01-07-2013
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1,2-Diamine derivatives are valuable building blocks to heterocyclic compounds and important precursors of biologically relevant compounds. In this respect, amino acid-derived ?-keto esters are a suitable starting point for the synthesis of ?,?-diamino ester derivatives through a two-step reductive amination procedure with either simple amines or ?-amino esters. AcOH and NaBH(3)CN are the additive and reducing agents of choice. The stereoselectivity of the reaction is still an issue, due to the slow imine-enamine equilibria through which the reaction occurs, affording mixtures of diastereoisomers that can be chromatographically separated. Transformation of the ?,?-diamino esters into pyrrolidinone derivatives allows the configuration assignment of the linear compounds, and constitutes an example of their potential application in the generation of molecular diversity.
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Biological effects of T315I-mutated BCR-ABL in an embryonic stem cell-derived hematopoiesis model.
Exp. Hematol.
PUBLISHED: 01-05-2013
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The occurrence of T315I mutation during the course of targeted therapies of chronic myeloid leukemia is a major concern because it confers resistance to all currently approved tyrosine kinase inhibitors. The exact phenotype of the hematopoietic stem cell and the hierarchical level of the occurrence of this mutation in leukemic hematopoiesis has not been determined. To study the effects of T315I-mutated breakpoint cluster region-abelson (BCR-ABL) in a primitive hematopoietic stem cell, we have used the murine embryonic stem cell (mESC)-derived hematopoiesis model. Native and T315I-mutated BCR-ABL were introduced retrovirally in mESC-derived embryonic bodies followed by induction of hematopoiesis. In several experiments, T315I-mutated and nonmutated BCR-ABL-transduced embryonic bodies rapidly generated hematopoietic cells on OP-9 feeders, with evidence of hematopoietic stem cell markers. After injection into NOD/SCID mice, these cells induced myeloid and lymphoid leukemias, whereas transplantation of control (nontransduced) hematopoietic cells failed to produce any hematopoietic reconstitution in vivo. Moreover, the expression of native and T315I-mutated BCR-ABL conferred to mESC-derived hematopoietic cells a self-renewal capacity demonstrated by the generation of leukemias after secondary transplantations. Secondary leukemias were more aggressive with evidence of extramedullary tumors. The expression of stem cell regulator Musashi-2 was found to be increased in bone marrow of leukemic mice. These data show that T315I-mutated BCR-ABL is functional at the stem cell level, conferring to mESC-derived leukemic cells a long-term hematopoietic repopulation ability. This model could be of interest to test the efficiency of drugs at the stem cell level in leukemias with T315I mutation.
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Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far.
Evid Based Complement Alternat Med
PUBLISHED: 01-04-2013
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The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2-20? ? M. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo.
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Incidence, clinical presentation, and antimicrobial resistance trends in Salmonella and Shigella infections from children in Yucatan, Mexico.
Front Microbiol
PUBLISHED: 01-01-2013
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Background: Salmonella and Shigella cause significant morbidity and mortality among children worldwide. Increased antimicrobial resistance results in greater burden of disease. Materials and Methods: From 2005 to 2011, Salmonella and Shigella isolates collected from ill children at a major hospital in Yucatan, Mexico, were subjected to serotyping and antimicrobial susceptibility testing by disk diffusion and agar dilution. The identification of bla CTX, bla CMY, bla SHV, bla TEM, and bla OXA and qnr resistance genes was conducted by PCR and sequencing. Results: Among 2344 children with acute gastroenteritis, salmonellosis decreased from 17.7% in 2005 to 11.2% in 2011 (p < 0.001). In contrast, shigellosis increased from 8.3% in 2010 to 12.1% in 2011. Compared to children with Salmonella, those with Shigella had significantly more bloody stools (59 vs 36%, p < 0.001), dehydration (27 vs 15%, p = 0.031), and seizures (11 vs 3%, p = 0.03). In Salmonella (n = 365), there was a significant decrease in resistance to ampicillin (43 to 16%, p < 0.001), trimethoprim-sulfamethoxazole (44 to 26%, p = 0.014), and extended-spectrum cephalosporins (27 to 10%, p = 0.009). Reduced susceptibility to ciprofloxacin in Salmonella rose from 30 to 41% (p < 0.001). All ceftriaxone-resistant isolates harbored the bla CMY-2 gene. qnr genes were found in 42 (36%) of the 117 Salmonella isolates with a ciprofloxacin MIC ? 0.125 ?g/ml. Four were qnrA1 and 38 were qnrB19. Resistance to ampicillin (40%) and trimethoprim-sulfamethoxazole (58%) was common in Shigella (n = 218), but isolates remained fully susceptible to ceftriaxone and ciprofloxacin. Conclusion: Illness from Salmonella has decreased while severe Shigella infections have increased among children with gastroenteritis in the Yucatan Peninsula. While Shigella resistance to clinically important antibiotics remained unchanged, resistance to most of these, except ciprofloxacin, declined in Salmonella. bla CMY-2 and qnr genes are common in Salmonella isolates.
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Threat perception and familiarity moderate the androgen response to competition in women.
Front Psychol
PUBLISHED: 01-01-2013
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Social interactions elicit androgen responses whose function has been posited to be the adjustment of androgen-dependent behaviors to social context. The activation of this androgen response is known to be mediated and moderated by psychological factors. In this study we tested the hypothesis that the testosterone (T) changes after a competition are not simply related to its outcome, but rather to the way the subject evaluates the event. In particular we tested two evaluative dimensions of a social interaction: familiarity with the opponent and the subjective evaluation of the outcome as threat or challenge. Challenge/threat occurs in goal relevant situations and represent different motivational states arising from the individuals subjective evaluation of the interplay between the task demands and coping resources possessed. For challenge the coping resources exceed the task demands, while threat represents a state where coping resources are insufficient to meet the task demands. In this experiment women competed in pairs, against a same sex opponent using the number tracking test as a competitive task. Losers appraised the competition outcome as more threatening than winners, and displayed higher post-competition T levels than winners. No differences were found either for cortisol (C) or for dehydroepiandrosterone. Threat, familiarity with the opponent and T response were associated only in the loser condition. Moderation analysis suggests that for the women that lost the competition the effect of threat on T is moderated by familiarity with the opponent.
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Strawberry processing does not affect the production and urinary excretion of urolithins, ellagic acid metabolites, in humans.
J. Agric. Food Chem.
PUBLISHED: 12-14-2011
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The study of fruit and vegetable processing and its effects on the levels of health-promoting constituents and their bioavailability and metabolism is very relevant to understanding the role of these constituents in human health. Strawberry polyphenols, and particularly ellagitannins and ellagic acid, have been associated with the health benefits of this berry for humans. These compounds are transformed into urolithins by the gut microbiota, and these metabolites exert several biological activities that could be responsible for the health effects of strawberries. Processing potentially increases the extraction of ellagitannins from the strawberry achenes and the release of ellagic acid from ellagitannins. It is of interest to evaluate the effect of processing on strawberry ellagitannin microbial metabolism compared with fresh strawberries. This study shows that no significant differences in the production and excretion of urolithins were found between the intake of fresh strawberries and that of a thermally processed strawberry puree containing the same amount of strawberries. Processing increases the amount of free ellagic acid 2.5-fold, but this had no effect on the transformation in urolithins by the gut microbiota or in the excretion of urolithin metabolites (urolithin glucuronides) in urine, showing that the release of ellagic acid from ellagitannins is not a relevant factor affecting the microbial metabolism. All of the volunteers produced urolithin A, but only 3 of 20 volunteers produced and excreted urolithin B. It is confirmed that some volunteers were efficient producers of urolithins, whereas other produced much lower amounts. These results show that processing does not modify the potential health effects of strawberry polyphenols.
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Analysis of protein fractions and some minerals present in chan (Hyptis suaveolens L.) seeds.
J. Food Sci.
PUBLISHED: 12-02-2011
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Chan (Hyptis suaveolens L.) seeds have been used as food as well as in traditional medicine in several countries of America, Asia and Africa. Chan seed protein content was 13.9% on dry weight basis. Analysis of its protein composition showed 39% globulins, 36% glutelins, 24% albumins, and 1% prolamins. By defatting the flour with chloroform/methanol, it increased the extracted proteins and improved the protein band resolution after SDS-PAGE, showing 5 albumin bands, 8 globulin bands, and 2 prolamin and glutelin bands. The aromatic amino acid content in chan seeds is higher than those of other grains including maize, with good levels of branched chain amino acids. In general, except for lysine, it has a well-balanced amino acid composition, providing a good supply of almost all the essential amino acids for the different age groups. Magnesium content was high, whereas calcium, potassium, and phosphorous were in the average range when compared to barley, oat, rice, and wheat. The present results indicate that seeds from the chan plant could be relevant because of their nutritional properties and they have the potential to be widely used in the production of high-quality food.
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Immunologic diseases and brain tumors.
Inflamm Allergy Drug Targets
PUBLISHED: 11-29-2011
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To do a bibliographic review of the given association of atopic [AD] and immunological diseases with central nerve system tumors [CNST] described a few years ago and to know the knowledge available. It gives an overview of the studies describing this association, and those explaining its mechanism. A negative association of AD with CNST stands out in case-control studies, which is not observed in cohort studies. The greatest association is seen for gliomas and is less significant for meningiomas. A clearer definition for the AD under study, tumour types, and the exact biochemical and clinical parameters to help diagnoses are the recommended as well as to establish an aetiologic and temporal relationship between AD and CNST.
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Postpartum amaurosis in a woman with severe preeclampsia.
Indian J Crit Care Med
PUBLISHED: 11-02-2011
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The maternal and perinatal fetal prognosis of preeclampsia depends on the gestational age of the fetus at onset, the severity of the disease, the quality of care, and the presence of pre-existent medical conditions. One of the uncommon effects of severe preeclampsia on the eye is sudden loss of vision. The present case report is of a woman with severe preeclampsia exacerbated by delivery that coursed with difficult-to-control arterial hypertension and reversible cortical amaurosis without impaired consciousness or seizures.
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[Clinical outcomes of 2 pediatric patients with Gauchers disease in enzyme replacement therapy for 9 years].
Med Clin (Barc)
PUBLISHED: 10-10-2011
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We report two cases of type 1 Gauchers disease in childhood and their outcomes after 9 years of enzyme replacement therapy. The first case concerns a 6-year-old boy who was diagnosed with Gauchers disease after developing petechial exanthema, thrombocytopenia, anemia and hepatosplenomegaly, coinciding with chickenpox. The second case involves a 9-year-old girl who was referred to our unit. She had hepatosplenomegaly since 4-month-old and subsequently developed thrombocytopenia. Both patients have the N370S/L444P mutation. Enzyme replacement therapy was started with 60 U/kg imiglucerase every 2 weeks at the age of 6 and 9 years, respectively. In both patients, the therapeutic goals were achieved and maintained throughout treatment with a dose of 30 U/kg.
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