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Find video protocols related to scientific articles indexed in Pubmed.
Intramedullary cervical abscess in the setting of aortic valve endocarditis.
Asian Cardiovasc Thorac Ann
PUBLISHED: 12-16-2014
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Spinal cord tissue has a remarkable resistance to infection. An intramedullary abscess is an exceptional complication of infective endocarditis in the post-antibiotic era. We describe the case of a 42-year-old man who presented with fever and cephalea. Two days later, left-side numbness, lack of sphincter control, and a new aortic murmur were noticed. Magnetic resonance imaging demonstrated an 8?×15-mm intramedullary cervical abscess. Transesophageal echocardiography revealed an aortic valve perforation as a result of infective endocarditis. Conservative management was decided for the intramedullary abscess.
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Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application.
Semin Ophthalmol
PUBLISHED: 11-14-2014
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Abstract Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric software using hemoglobin as the reference pigment in the papilla, was used for the analysis. The papilla of these multiple sclerosis patients showed greater pallor, especially in the temporal sector. The software detected the pallor and assigned hemoglobin percentages below normal reference values. Measurements of optic disc hemoglobin levels obtained with the Laguna ONhE software program had good ability to detect optic atrophy and, consequently, axonal loss in multiple sclerosis patients. This new technology is easy to implement in routine clinical practice.
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Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice.
Brain
PUBLISHED: 11-14-2014
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Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients' antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients' antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients' or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients' cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days 13-18), that after acid extraction and characterization with GluN1-expressing human embryonic kidney cells were confirmed to be against the NMDAR. Confocal microscopy and immunoblot analysis of the hippocampus showed progressive decrease of the density of total and synaptic NMDAR clusters and total NMDAR protein concentration (maximal on Day 18), without affecting the post-synaptic density protein 95 (PSD95) and ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These effects occurred in parallel with memory and other behavioural deficits and gradually improved after Day 18, with reversibility of symptoms accompanied by a decrease of brain-bound antibodies and restoration of NMDAR levels. Overall, these findings establish a link between memory and behavioural deficits and antibody-mediated reduction of NMDAR, provide the biological basis by which removal of antibodies and antibody-producing cells improve neurological function, and offer a model for testing experimental therapies in this and similar disorders.
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Frustrated expected reward induces differential transcriptional changes in the mouse brain.
Addict Biol
PUBLISHED: 10-08-2014
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Frustration represents a particular aspect of the addictive process that is related to loss of control when the expected reward is not obtained. We aim to study the consequences of frustrated expected reward on gene expression in the mouse brain. For this purpose, we used an operant model of frustration using palatable food as reward combined with microarrays. Transcriptomic profiles of frontal cortex, ventral striatum and hippocampus were analysed in five groups of mice: (1) positive control receiving palatable food and the cue light as conditioned stimulus; (2) frustrated group only receiving the cue light; (3) extinction learning group that did not receive palatable food nor the light; (4) negative control that never received the reinforcer nor the light during the whole experiment; and (5) yoked that received palatable food passively. Gene expression changes produced by frustration were revealed in the frontal cortex and ventral striatum, but not in the hippocampus. Most of the changes, such as the modification of the dopamine-DARPP-32 signalling pathway, were common in both areas and estimated to have neuronal origin. Extinction learning induced transcriptional changes only in the ventral striatum, with most genes showing down-regulation and without alteration in the dopamine-DARPP-32 signalling pathway. Active palatable food-seeking behaviour induced changes in gene expression in ventral striatum mainly affecting cell communication. In conclusion, frustration behaviour-induced changes in frontal cortex and ventral striatum mainly related to dopamine-DARPP-32 signalling that could play an important role in the loss of behavioural control during the addictive processes.
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Proyecto MercadoFRESCO: A Multi-level, Community-Engaged Corner Store Intervention in East Los Angeles and Boyle Heights.
J Community Health
PUBLISHED: 09-12-2014
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Urban food swamps are typically situated in low-income, minority communities and contribute to overweight and obesity. Changing the food landscape in low income and underserved communities is one strategy to combat the negative health consequences associated with the lack of access to healthy food resources and an abundance of unhealthy food venues. In this paper, we describe Proyecto MercadoFRESCO (Fresh Market Project), a corner store intervention project in East Los Angeles and Boyle Heights in California that used a multi-level approach with a broad range of community, business, and academic partners. These are two neighboring, predominantly Latino communities that have high rates of overweight and obesity. Located in these two communities are approximately 150 corner stores. The project used a community-engaged approach to select, recruit, and convert four corner stores, so that they could become healthy community assets in order to improve residents' access to and awareness of fresh and affordable fruits and vegetables in their immediate neighborhoods. We describe the study framework for the multi-level intervention, which includes having multiple stakeholders, expertise in corner store operations, community and youth engagement strategies, and social marketing campaigns. We also describe the evaluation and survey methodology to determine community and patron impact of the intervention. This paper provides a framework useful to a variety of public health stakeholders for implementing a community-engaged corner store conversion, particularly in an urban food swamp.
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Mediterranean diet and cardiodiabesity: a review.
Nutrients
PUBLISHED: 09-04-2014
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Cardiodiabesity has been used to define and describe the well-known relationship between type 2 Diabetes Mellitus (T2DM), obesity, the metabolic syndrome (MetS) and cardiovascular disease (CVD). The objective of this study was to perform a scientific literature review with a systematic search to examine all the cardiovascular risk factors combined and their relationship with adherence to the Mediterranean Diet (MedDiet) pattern as primary prevention against cardiodiabesity in a holistic approach. Research was conducted using the PubMed database including clinical trials, cross-sectional and prospective cohort studies. Thirty-seven studies were reviewed: fourteen related to obesity, ten to CVD, nine to MetS, and four to T2DM. Indeed 33 provided strong evidence on the association between adherence to a MedDiet and a reduced incidence of collective cardiodiabesity risk in epidemiological studies. This scientific evidence makes the MedDiet pattern very useful for preventive strategies directed at the general population and also highlights the need to consider all these diet-related risk factors and health outcomes together in daily primary care.
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Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ.
Breast Cancer Res.
PUBLISHED: 09-04-2014
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Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS.
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The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.
Hum. Mol. Genet.
PUBLISHED: 08-22-2014
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Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to discover putative therapeutic targets. MELAS syndrome is a rare neurodegenerative disease caused by mutations in mitochondrial (mt) DNA affecting mt-tRNA(Leu(UUR)). Patient and cybrid cells exhibit elevated oxidative stress. Moreover, mutant mt-tRNAs(Leu(UUR)) lack the taurine-containing modification normally present at the wobble uridine (U34) of wild-type mt-tRNA(Leu(UUR)), which is considered an etiology of MELAS. However, the molecular mechanism is still unclear. We found that MELAS cybrids exhibit a significant decrease in the steady-state levels of several mt-tRNA-modification enzymes, which is not due to transcriptional regulation. We demonstrated that oxidative stress mediates an NFkB-dependent induction of microRNA-9/9*, which acts as a post-transcriptional negative regulator of the mt-tRNA-modification enzymes GTPBP3, MTO1 and TRMU. Down-regulation of these enzymes by microRNA-9/9* affects the U34 modification status of non-mutant tRNAs and contributes to the MELAS phenotype. Anti-microRNA-9 treatments of MELAS cybrids reverse the phenotype, whereas miR-9 transfection of wild-type cells mimics the effects of siRNA-mediated down-regulation of GTPBP3, MTO1 and TRMU. Our data represent the first evidence that an mt-DNA disease can directly affect microRNA expression. Moreover, we demonstrate that the modification status of mt-tRNAs is dynamic and that cells respond to stress by modulating the expression of mt-tRNA-modifying enzymes. microRNA-9/9* is a crucial player in mitochondria-to-nucleus signaling as it regulates expression of nuclear genes in response to changes in the functional state of mitochondria.
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Clinical practice guidelines for translating pharmacogenomic knowledge to bedside. Focus on anticancer drugs.
Front Pharmacol
PUBLISHED: 08-19-2014
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The development of clinical practice recommendations or guidelines for the clinical use of pharmacogenomics data is an essential issue for improving drug therapy, particularly for drugs with high toxicity and/or narrow therapeutic index such as anticancer drugs. Although pharmacogenomic-based recommendations have been formulated for over 40 anticancer drugs, the number of clinical practice guidelines available is very low. The guidelines already published indicate that pharmacogenomic testing is useful for patient selection, but final dosing adjustment should be carried out on the basis of clinical or analytical parameters rather than on pharmacogenomic information. Patient selection may seem a modest objective, but it constitutes a crucial improvement with regard to the pre-pharmacogenomics situation and it saves patients' lives. However, we should not overstate the current power of pharmacogenomics. At present the pharmacogenomics of anticancer drugs is not sufficiently developed for dose adjustments based on pharmacogenomics only, and no current guidelines recommend such adjustments without considering clinical and/or analytical parameters. This objective, if ever attained, would require the use of available guidelines, further implementation with clinical feedback, plus a combination of genomics and phenomics knowledge.
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Neural Network Analysis of Different Segmentation Strategies of Nerve Fiber Layer Assessment for Glaucoma Diagnosis.
J. Glaucoma
PUBLISHED: 07-24-2014
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To compare the diagnostic performance of different segmentations of the nerve fiber layer (NFL) thickness measurements using an artificial neural network and to define the optimal number of sectors with best diagnostic ability for glaucoma diagnosis.
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Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole.
Biochem. Pharmacol.
PUBLISHED: 07-22-2014
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Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity.
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Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome.
J Neural Transm
PUBLISHED: 07-15-2014
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Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.
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Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for potency, selectivity, and half-life.
J. Biol. Chem.
PUBLISHED: 06-17-2014
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Ion channels are an attractive class of drug targets, but progress in developing inhibitors for therapeutic use has been limited largely due to challenges in identifying subtype selective small molecules. Animal venoms provide an alternative source of ion channel modulators, and the venoms of several species, such as scorpions, spiders and snails, are known to be rich sources of ion channel modulating peptides. Importantly, these peptides often bind to hyper-variable extracellular loops, creating the potential for subtype selectivity rarely achieved with small molecules. We have engineered scorpion venom peptides and incorporated them in fusion proteins to generate highly potent and selective Kv1.3 inhibitors with long in vivo half-lives. Kv1.3 has been reported to play a role in human T cell activation, and therefore, these Kv1.3 inhibitor fusion proteins may have potential for the treatment of autoimmune diseases. Our results support an emerging approach to generating subtype selective therapeutic ion channel inhibitors.
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Effects of genetic deletion of endogenous opioid system components on the reinstatement of cocaine-seeking behavior in mice.
Neuropsychopharmacology
PUBLISHED: 05-30-2014
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The repeated cycles of cessation of consumption and relapse remain the major clinical concern in treating drug addiction. The endogenous opioid system is a crucial component of the reward circuit that participates in the adaptive changes leading to relapse in the addictive processes. We have used genetically modified mice to evaluate the involvement of ?-opioid receptor (MOR) and ?-opioid receptor (DOR) and their main endogenous ligands, the enkephalins derived from proenkephalin (PENK) and prodynorphin (PDYN), in the reinstatement of cocaine-seeking behavior. Constitutive knockout mice of MOR, DOR, PENK, and PDYN, and their wild-type littermates were trained to self-administer cocaine or to seek for palatable food, followed by a period of extinction and finally tested on a cue-induced reinstatement of seeking behavior. The four lines of knockout mice acquired operant cocaine self-administration behavior, although DOR and PENK knockout mice showed less motivation for cocaine than wild-type littermates. Moreover, cue-induced relapse was significantly decreased in MOR and DOR knockout mice. In contrast, PDYN knockout mice showed a slower extinction and increased relapse than wild-type littermates. C-Fos expression analysis revealed differential activation in brain areas related with memory and reward in these knockout mice. No differences were found in any of the four genotypes in operant responding to obtain palatable food, indicating that the changes revealed in knockout mice were not due to unspecific deficit in operant performance. Our results indicate that MOR, DOR, and PDYN have a differential role in cue-induced reinstatement of cocaine-seeking behavior.
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Survival after major cardiac surgery: performance and comparison of predictive ability of EuroSCORE II and logistic EuroSCORE in a sample of Mediterranean population.
Thorac Cardiovasc Surg
PUBLISHED: 05-28-2014
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The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II has been recently introduced to improve mortality prediction in cardiac surgery. We compare the predictive ability of the new EuroSCORE II with that of the original logistic EuroSCORE and we made an evaluation of a sample of our population submitted to major cardiac surgery in the context of a Mediterranean country.
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rpoD gene pyrosequencing for the assessment of Pseudomonas diversity in a water sample from the Woluwe River.
Appl. Environ. Microbiol.
PUBLISHED: 05-27-2014
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A water sample from a noncontaminated site at the source of the Woluwe River (Belgium) was analyzed by culture-dependent and -independent methods. Pseudomonas isolates were identified by sequencing and analysis of the rpoD gene. Cultureindependent methods consisted of cloning and pyrosequencing of a Pseudomonas rpoD amplicon from total DNA extracted from the same sample and amplified with selective rpoD gene primers. Among a total of 14,540 reads, 6,228 corresponded to Pseudomonas rpoD gene sequences by a BLAST analysis in the NCBI database. The selection criteria for the reads were sequences longer than 400 bp, an average Q40 value greater than 25, and>85% identity with a Pseudomonas species. Of the 6,228 Pseudomonas rpoD sequences, 5,345 sequences met the established criteria for selection. Sequences were clustered by phylogenetic analysis and by use of the QIIME software package. Representative sequences of each cluster were assigned by BLAST analysis to a known Pseudomonas species when the identity with the type strain was greater than or equal to 96%. Twenty-six species distributed among 12 phylogenetic groups or subgroups within the genus were detected by pyrosequencing. Pseudomonas stutzeri, P. moraviensis, and P. simiae were the only cultured species not detected by pyrosequencing. The predominant phylogenetic group within the Pseudomonas genus was the P. fluorescens group, as determined by culture-dependent and -independent analyses. In all analyses, a high number of putative novel phylospecies was found: 10 were identified in the cultured strains and 246 were detected by pyrosequencing, indicating that the diversity of Pseudomonas species has not been fully described.
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COMT gene and risk for Parkinson's disease: a systematic review and meta-analysis.
Pharmacogenet. Genomics
PUBLISHED: 05-14-2014
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Several single-nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene have been associated with the risk of developing Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on PD risk related with COMT SNPs (mainly rs4680). We also reviewed the possible relationship of COMT SNPs with clinical, neuropharmacological, neurochemical, and neuroimaging features of PD.
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A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients.
Clin. Cancer Res.
PUBLISHED: 05-01-2014
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Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC).
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Potential new diagnostic tool for Alzheimer's disease using a linear discriminant function for Fourier domain optical coherence tomography.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 04-17-2014
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We calculated and validated a linear discriminant function (LDF) for Fourier domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in the detection of Alzheimer's disease (AD).
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Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer.
Tumour Biol.
PUBLISHED: 03-27-2014
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Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an increasingly recognized role in tumour biology. The aim of this study was to explore the role of DUSP6 expression in the prognosis of human non-small cell lung cancer (NSCLC). DUSP6 expression levels were evaluated by real-time quantitative reverse transcription polymerase chain reaction (PCR) in 60 NSCLC samples from patients who underwent pulmonary resection at 12 de Octubre University Hospital. We performed a statistical analysis to investigate the correlation of DUSP6 expression and the clinical outcomes. We found that 66.7 % of the tumour samples show the downregulation of DUSP6 at the messenger RNA (mRNA) levels compared to benign epithelial lung tissues and 55 % of them show at least twofold downregulation of DUSP6 gene expression. Patients were classified into three groups according to their DUSP6 expression levels and those with very low levels (at least twofold downregulation) had the worst outcomes. Using the value of twice below the mean value in benign epithelial lung tissue as a cutoff, the overall survival of patients with very low DUSP6 levels was significantly lower than that in the rest of patients (31.9?±?18.8 months vs. not reached, P?=?0.049). This was most pronounced in adenocarcinoma histology and high-stage tumour samples. Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC.
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A bovine aortic arch in humans.
Indian Heart J
PUBLISHED: 03-23-2014
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We describe a curious congenital variation of human aortic arch (AA) branching pattern termed the "bovine aortic arch". Rather than arising directly from the AA as a separate branch as occurs in the most common AA branching pattern, the left common carotid artery moves to the right and merges from the brachiocephalic trunk. It is the normal AA branching pattern presented in a number of animals (canines, felines or Macaque monkeys) but it has nothing to do with anatomy of AA in ruminant animals, including cattle and buffalo. That is why it is one of the most widely misnomers used in medical literature whose origin is nowadays unknown.
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Relationships between serotonergic and cannabinoid system in depressive-like behavior: a PET study with [11C]-DASB.
J. Neurochem.
PUBLISHED: 03-17-2014
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Chronic stress represents a major environmental risk factor for mood disorders in vulnerable individuals. The neurobiological mechanisms underlying these disorders involve serotonergic and endocannabinoid systems. In this study, we have investigated the relationships between these two neurochemical systems in emotional control using genetic and imaging tools. CB1 cannabinoid receptor knockout mice (KO) and wild-type littermates (WT) were exposed to chronic restraint stress. Depressive-like symptoms (anhedonia and helplessness) were produced by chronic stress exposure in WT mice. CB1 KO mice already showed these depressive-like manifestations in non-stress conditions and the same phenotype was observed after chronic restraint stress. Chronic stress similarly impaired long-term memory in both genotypes. In addition, brain levels of serotonin transporter (5-HTT) were assessed using positron emission tomography. Decreased brain 5-HTT levels were revealed in CB1 KO mice under basal conditions, as well as in WT mice after chronic stress. Our results show that chronic restraint stress induced depressive-like behavioral alterations and brain changes in 5-HTT levels similarly to those revealed in CB1 KO mice in non-stressed conditions. These results underline the relevance of chronic environmental stress on serotonergic and endocannabinoid transmission for the development of depressive symptoms. Chronic restraint stress induces depressive-like behavior and reduced 5-HTT levels in WT mice similar to those revealed in non-stressed CB1-KO mice. Reduced 5-HTT in both genotypes increases synaptic 5-HT concentration. The 5-HT release is modulated through CB1 receptors and the absence of inhibitory CB1 receptor causes decreased inhibition of 5-HT release resulting in high synaptic 5-HT concentration that are not further enhanced by stress.
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Frequency of cocaine self-administration influences drug seeking in the rat: optogenetic evidence for a role of the prelimbic cortex.
Neuropsychopharmacology
PUBLISHED: 03-09-2014
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High-frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to have a role in cocaine seeking. However, their involvement in regulating high-frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect on Low frequency rats. Thus, high-frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.
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A concealed atriopleural fistula resulting from a cardiac stab wound.
Rev Port Cardiol
PUBLISHED: 03-04-2014
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A young male presented with a right parasternal stab wound. The chest radiography was normal and transthoracic echocardiography ruled out pericardial tamponade. He remained hemodynamically stable until three hours later when signs of progressive anemia were observed. Chest computed tomography showed massive right-sided hemothorax. The patient underwent surgery, which revealed an active bleeding atriopleural fistula connecting the right atrium and draining into the right pleura resulting from the negative pressure generated during respiration. This mechanism prevented cardiac tamponade and maintained initial hemodynamically stability.
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Correlation between aneuploidy, apoptotic markers and DNA fragmentation in spermatozoa from normozoospermic patients.
Reprod. Biomed. Online
PUBLISHED: 03-04-2014
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Genetic and biochemical sperm integrity is essential to ensure the reproductive competence. However, spermatogenesis involves physiological changes that could endanger sperm integrity. DNA protamination and apoptosis have been studied extensively. Furthermore, elevated rates of aneuploidy and DNA injury correlate with reproductive failures. Consequently, this study applied the conventional spermiogram method in combination with molecular tests to assess genetic integrity in ejaculate from normozoospermic patients with implantation failure by retrospectively analysing aneuploidy (chromosomes 18, X, Y), DNA fragmentation, externalization of phosphatidylserine and mitochondrial membrane potential status before and after magnetic activated cell sorting (MACS). Aneuploid, apoptotic and DNA-injured spermatozoa decreased significantly after MACS. A positive correlation was detected between reduction of aneuploidy and decreased DNA damage, but no correlation was determined with apoptotic markers. The interactions between apoptotic markers, DNA integrity and aneuploidy, and the effect of MACS on these parameters, remain unknown. In conclusion, use of MACS reduced aneuploidy, DNA fragmentation and apoptosis. A postulated mechanism relating aneuploidy and DNA injury is discussed; on the contrary, cell death markers could not be related. An 'apoptotic-like' route could explain this situation.
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Protein tyrosine phosphatase PTPN22 +1858C/T polymorphism is associated with active vitiligo.
Exp Ther Med
PUBLISHED: 02-21-2014
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Vitiligo is characterized by a skin depigmentation disorder resulting from an autoimmune response targeting melanocytes. Within the genetic factors involved in the development of the vitiligo immune response, various genes in the major histocompatibility complex (MHC) and non-MHC loci have been considered to be risk factors. The PTPN22 gene encodes for a lymphoid protein tyrosine phosphatase, a regulator of the activation and development of T-cells. The +1858C/T polymorphism has been associated to autoimmune disease susceptibility in different populations and could be implicated in the onset of vitiligo. To assess the possible association between the presence of PTPN22 +1858C/T and vitiligo, 187 patients with vitiligo and 223 control subjects were analyzed in the study. Genomic DNA was isolated using the salting-out method and samples were subjected to polymerase chain reaction-restriction fragment length polymorphism in order to detect the PTPN22 +1858C/T polymorphism. Causal associations were determined by ?(2) test and their respective odds ratio (OR) was assessed in a 2×2 contingency table. The results showed an association between active vitiligo and the allele T load [P=0.0418; OR, 2.5706; 95% confidence interval (CI), 1.0040-6.5816], and active vitiligo-CT genotype (P=0.0389, OR, 2.6548; 95% CI, 1.0191-6.9156). In conclusion, the present data indicates a possible association between the PTPN22 +1858C/T genotype and a significant susceptibility of developing an active form of vitiligo.
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PITX3 and risk for Parkinson's disease: a systematic review and meta-analysis.
Eur. Neurol.
PUBLISHED: 02-15-2014
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Several single nucleotide polymorphisms (SNPs) in the PITX3 gene have been associated with the risk for Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on the risk of PD related with these polymorphisms.
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Phase II Trial of Target-guided Personalized Chemotherapy in First-line Metastatic Colorectal Cancer.
Am. J. Clin. Oncol.
PUBLISHED: 02-13-2014
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The aim of this study was to investigate the feasibility and efficacy of personalizing treatment of patients with advanced untreated colorectal cancer (CRC).
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NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis.
BMC Neurol
PUBLISHED: 02-12-2014
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A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population.
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Gene variants and haplotypes modifying transcription factor binding sites in the human cyclooxygenase 1 and 2 (PTGS1 and PTGS2) genes.
Curr. Drug Metab.
PUBLISHED: 01-18-2014
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Cyclooxygenases (prostaglandin-endoperoxide synthases, (EC 1.14.99.1) 1 and 2 (COX-1 and COX-2)) are key enzymes with a highly functional and pharmacological relevance. Genetic variations in the corresponding genes PTGS1 and PTGS2 are related to diverse human disorders and adverse drug reactions. Although COX-2 is highly inducible, most genetic association studies have focused on coding region gene variants. The aim of this study is to analyze the genetic variants modifying transcription factor binding sites in human PTGS genes based on the combined use of bioinformatics with 1,000 genomes data and replication by next generation sequencing. Updated information on gene sequences and variants was obtained from the 1,000 genomes website and from a replication sequencing study. Of the 570 upstream PTGS1 gene variants, 43 altered binding sites, either by disrupting existing sequences or by creating new binding sites. The most relevant are the SNP rs72769722, which creates a new binding site for NFKB, and the SNPs rs73559017 and rs76403914, both disrupting binding sites for CDX1. Of the 682 upstream PTGS2 gene variants, 31 altered binding sites, the most relevant being rs689466 and rs20417, which disrupt binding sequences for MYB and E2F, respectively; rs689462 which creates a new binding site for POU3F2; and a haplotype combining the SNPs rs34984585+rs10911904, which creates a new binding site for SRY. This study provides a detailed catalog of variant and invariant transcription factor binding sites for PTGS genes and related haplotypes. This information can be useful to identify potential genetic targets for studies related to COX enzymes.
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Genomic and pharmacogenomic biomarkers of Parkinson's disease.
Curr. Drug Metab.
PUBLISHED: 01-18-2014
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The relative role of genetic and environmental factors in the pathogenesis of Parkinson's disease (PD) has been the matter of investigation and debate, especially in the last 30 years. The possible interaction between genetic and environmental factors led to a great number of association studies between single nucleotide polymorphisms (SNPs) of many candidate genes and PD risk. In this study we summarized and critically reviewed the results of studies published on this issue, with especial reference to those reported in the last 5 years. Many studies provided conflicting findings and, when positive associations were identified, associations were weak. Polymorphisms related with activation or detoxification of drugs and xenobiotics, such as CYP1A1, CYP1A2, CYP19A1, CYP1B1, CYP2C9, CYP2C19, CYP2E1, CYP2D6, NAT2, GSTM1, GSTM3, GSTO1, GSTP1, PON1, PON2, ABCB1 and ADH genes have not been demonstrated convincingly a definitive association with the risk of developing PD. Nor did polymorphisms in genes related to dopamine or serotonin DRD, DAT, TH, DDC, DBH, MAO, COMT, SLC6A4, MTR, MTHFR, oxidative stress NOQ1, NOQ2, mEPHX, HFE, GPX, CAT, mnSOD, HFE, HO-1, HO-2, NFE2L2, KEAP1, inflammatory processes, ILs, TNF, ACT, NOS, HNMT, ABP1, HRHs, trophic and growth factors BDNF, FGF, or mitochondrial metabolism and function. In addition we analyzed other putative relations and genes associated with monogenic familial PD.Taking together the results of candidate gene association studies and genome wide association studies, only some SNPs of the MAPT, SNCA, HLA and GBA genes seem to be the most likely associated with PD risk.
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Perception of the usefulness of drug/gene pairs and barriers for pharmacogenomics in Latin America.
Curr. Drug Metab.
PUBLISHED: 01-18-2014
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Pharmacogenetics and Pharmacogenomics areas are currently emerging fields focused to manage pharmacotherapy that may prevent undertreatment while avoiding associated drug toxicity in patients. Large international differences in the awareness and in the use of pharmacogenomic testing are presumed, but not well assessed to date. In the present study we review the awareness of Latin American scientific community about pharmacogenomic testing and the perceived barriers for their clinical application. In order to that, we have compiled information from 9 countries of the region using a structured survey which is compared with surveys previously performed in USA and Spain. The most relevant group of barriers was related to the need for clear guidelines for the use of pharmacogenomics in clinical practice, followed by insufficient awareness about pharmacogenomics among clinicians and the absence of regulatory institutions that facilitate the use of pharmacogenetic tests. The higher ranked pairs were TPMT/thioguanine, TPMT/azathioprine, CYP2C9/warfarin, UGT1A1/irinotecan, CYP2D6/amitriptiline, CYP2C19/citalopram and CYP2D6/clozapine. The lower ranked pairs were SLCO1B1/simvastatin, CYP2D6/metoprolol and GP6D/chloroquine. Compared with USA and Spanish surveys, 25 pairs were of lower importance for Latin American respondents. Only CYP2C19/esomeprazole, CYP2C19/omeprazole, CYP2C19/celecoxib and G6PD/dapsone were ranked higher or similarly to the USA and Spanish surveys. Integration of pharmacogenomics in clinical practice needs training of healthcare professionals and citizens, but in addition legal and regulatory guidelines and safeguards will be needed. We propose that the approach offered by pharmacogenomics should be incorporated into the decision-making plans in Latin America.
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Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-16-2014
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To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD).
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The solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, rs3794087 variant and assessment risk for restless legs syndrome.
Sleep Med.
PUBLISHED: 01-16-2014
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A glutamatergic dysfunction has been postulated to play a role in restless legs syndrome (RLS) pathophysiology, as glutamate concentrations have been found to increase in the thalamus of RLS patients. The aim of our study was to investigate the possible association between the single nucleotide polymorphism (SNP) rs3794087 in the solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, related with glutamate transport and the risk for RLS.
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SLC1A2 rs3794087 variant and risk for migraine.
J. Neurol. Sci.
PUBLISHED: 01-14-2014
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Glutamate has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism rs3794087 in the SLC1A2 gene (EATT2 or GLT-1; chromosome 11p13-p12 involved in glutamate transport) and the risk for migraine and for triggering migraine attacks by alcohol.
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Successful retrieval of an irretrievable jugular tesio catheter using a fogarty arterial embolectomy catheter.
Vasc Endovascular Surg
PUBLISHED: 01-09-2014
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Long life expectancy and wide development of therapies have increased the number of patients under artificial treatment for lost kidney function or dialysis. Different options for vascular access are suitable for receiving this therapy. The use of tunneled catheters has consequently increased complications related to its use. A difficult retrieval of catheters caused by a hard fibrin sheath along its trajectory is a common drawback. Herein, we report a woman with suspicion of hemodialysis catheter infection and an irretrievable Tesio catheter. A novel technique using a Fogarty arterial catheter allowed a successful retrieval and avoided an aggressive management.
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Pregnenolone can protect the brain from cannabis intoxication.
Science
PUBLISHED: 01-04-2014
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Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), ?(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
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Drug and xenobiotic biotransformation in the blood-brain barrier: a neglected issue.
Front Cell Neurosci
PUBLISHED: 01-01-2014
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Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB) has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to the BBB as a drug-metabolizing barrier. The presence of drug-metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.
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Genome Analysis of Environmental and Clinical P. aeruginosa Isolates from Sequence Type-1146.
PLoS ONE
PUBLISHED: 01-01-2014
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The genomes of Pseudomonas aeruginosa isolates of the new sequence type ST-1146, three environmental (P37, P47 and P49) and one clinical (SD9) isolates, with differences in their antibiotic susceptibility profiles have been sequenced and analysed. The genomes were mapped against P. aeruginosa PAO1-UW and UCBPP-PA14. The allelic profiles showed that the highest number of differences were in "Related to phage, transposon or plasmid" and "Secreted factors" categories. The clinical isolate showed a number of exclusive alleles greater than that for the environmental isolates. The phage Pf1 region in isolate SD9 accumulated the highest number of nucleotide substitutions. The ORF analysis of the four genomes assembled de novo indicated that the number of isolate-specific genes was higher in isolate SD9 (132 genes) than in isolates P37 (24 genes), P47 (16 genes) and P49 (21 genes). CRISPR elements were found in all isolates and SD9 showed differences in the spacer region. Genes related to bacteriophages F116 and H66 were found only in isolate SD9. Genome comparisons indicated that the isolates of ST-1146 are close related, and most genes implicated in pathogenicity are highly conserved, suggesting a genetic potential for infectivity in the environmental isolates similar to the clinical one. Phage-related genes are responsible of the main differences among the genomes of ST-1146 isolates. The role of bacteriophages has to be considered in the adaptation processes of isolates to the host and in microevolution studies.
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An association study between Heme oxygenase-1 genetic variants and Parkinson's disease.
Front Cell Neurosci
PUBLISHED: 01-01-2014
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The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT) n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT) n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk.
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Mitochondrial DAMPs induce endotoxin tolerance in human monocytes: an observation in patients with myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Monocyte exposure to mitochondrial Danger Associated Molecular Patterns (DAMPs), including mitochondrial DNA (mtDNA), induces a transient state in which these cells are refractory to further endotoxin stimulation. In this context, IRAK-M up-regulation and impaired p65 activity were observed. This phenomenon, termed endotoxin tolerance (ET), is characterized by decreased production of cytokines in response to the pro-inflammatory stimulus. We also show that monocytes isolated from patients with myocardial infarction (MI) exhibited high levels of circulating mtDNA, which correlated with ET status. Moreover, a significant incidence of infection was observed in those patients with a strong tolerant phenotype. The present data extend our current understanding of the implications of endotoxin tolerance. Furthermore, our data suggest that the levels of mitochondrial antigens in plasma, such as plasma mtDNA, should be useful as a marker of increased risk of susceptibility to nosocomial infections in MI and in other pathologies involving tissue damage.
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Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.
PLoS ONE
PUBLISHED: 01-01-2014
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Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13 × 10(-6)), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.
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Variability in histamine receptor genes HRH1, HRH2 and HRH4 in patients with hypersensitivity to NSAIDs.
Pharmacogenomics
PUBLISHED: 11-19-2013
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Histamine plays an important role in the pathogenesis of allergic diseases. Genetic variations in histamine receptors (HRH) may influence the expression of allergic diseases. This study analyzes the association between HRH variants and NSAID hypersensitivity reactions.
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Draft Genome Sequence of Pseudomonas azotifigens Strain DSM 17556T (6H33bT), a Nitrogen Fixer Strain Isolated from a Compost Pile.
Genome Announc
PUBLISHED: 11-02-2013
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Pseudomonas azotifigens strain 6H33b(T) is a nitrogen fixer isolated from a hyperthermal compost pile in 2005 by Hatayama and collaborators. Here we report the draft genome, which has an estimated size of 5.0 Mb, exhibits an average G+C content of 66.73%, and is predicted to encode 4,536 protein-coding genes and 100 RNA genes.
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Influence of cataract surgery on repeatability and measurements of spectral domain optical coherence tomography.
Br J Ophthalmol
PUBLISHED: 10-30-2013
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To evaluate the effect of uncomplicated cataract phacoemulsification on the measurements of macular and retinal nerve fibre layer (RNFL) in healthy subjects using two spectral domain (SD) optical coherence tomography (OCT) instruments-Cirrus OCT (Zeiss) and Spectralis OCT (Heidelberg)-and to assess the reliability of the measurements obtained with these two devices before and after cataract surgery.
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Retinal segmentation as noninvasive technique to demonstrate hyperplasia in ataxia of Charlevoix-Saguenay.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-12-2013
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To present a new retinal layer segmentation technique for evaluation of nerve fiber hyperplasia in patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
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E1a promotes c-Myc-dependent replicative stress: Implications in glioblastoma radiosensitization.
Cell Cycle
PUBLISHED: 10-11-2013
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The E1a gene from adenovirus is known to be a potent inducer of chemo/radiosensitivity in a wide range of tumors. However, the molecular bases of its radiosensitizer properties are still poorly understood. In an attempt to study this effect, U87MG cells, derived from a radio-resistant tumor as glioblastoma, where infected with lentivirus carrying E1a gene developing an acute sensitivity to ionizing radiation. The induction of radiosensitivity correlated with a marked G 2/M phase accumulation and a potent apoptotic response. Our findings demonstrate that c-Myc plays a pivotal role in E1a-associated radiosensitivity through the induction of a replicative stress situation, as our data support by genetic approaches, based in interference and overexpression in U87MG cells. In fact, we present evidence showing that Chk1 is a novel transcriptional target of E1a gene through the effect exerted by this adenoviral protein onto c-Myc. Moreover, c-Myc upregulation also explains the marked phosphorylation of H2AX associated to E1a expression in the absence of DNA damage. Indeed, all these observations were applicable to other experimental models, such as T98G, LN-405 and A172, rendering the same pattern in terms of radiosensitivity, cell cycle distribution, upregulation of Chk1, c-Myc, and phosphorylation pattern of H2AX. In summary, our data propose a novel mechanism to explain how E1a mediates radiosensitivity through the signaling axis E1a?c-Myc? replicative stress situation. This novel mechanism of E1a-mediated radiosensitivity could be the key to open new possibilities in the current therapy of glioblastoma.
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Diagnostic ability of a new method for measuring haemoglobin levels in the optic nerve head in multiple sclerosis patients.
Br J Ophthalmol
PUBLISHED: 09-30-2013
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To evaluate a new method for measuring haemoglobin (Hb) levels and quantifying the colour changes in the optic nerve head of multiple sclerosis (MS) patients to detect axonal loss and consequently optic disc atrophy.
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Artificial Neural Network Techniques to Improve the Ability of Optical Coherence Tomography to Detect Optic Neuritis.
Semin Ophthalmol
PUBLISHED: 08-20-2013
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ABSTRACT Purpose: To analyze the ability of Spectralis optical coherence tomography (OCT) to detect multiple sclerosis (MS) and to distinguish MS eyes with antecedent optic neuritis (ON). To analyze the capability of artificial neural network (ANN) techniques to improve the diagnostic precision. Methods: MS patients and controls were enrolled (n?=?217). OCT was used to determine the 768 retinal nerve fiber layer thicknesses. Sensitivity and specificity were evaluated to test the ability of OCT to discriminate between MS and healthy eyes, and between MS with and without antecedent ON using ANN. Results: Using ANN technique multilayer perceptrons, OCT could detect MS with a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic precision of 88.5%. Compared with the OCT-provided parameters, the ANN had a better sensitivity-specificity balance. Conclusions: ANN technique improves the capability of Spectralis OCT to detect MS disease and to distinguish MS eyes with or without antecedent ON.
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No association of the SLC1A2 rs3794087 allele with risk for essential tremor in the Spanish population.
Pharmacogenet. Genomics
PUBLISHED: 08-17-2013
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A recent genome-wide association study and other replication studies have suggested that the rs3794087 single nucleotide polymorphism in the solute carrier family 1 - glial affinity glutamate transporter-member 2 (SLC1A2) gene is associated with an increased risk for essential tremor (ET), and a replication study in an Asian cohort has shown a decreased risk for ET associated with the rs3794087T allele. We tried to replicate this association in a White Spanish population.
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Draft Genome Sequence of Pseudomonas stutzeri Strain B1SMN1, a Nitrogen-Fixing and Naphthalene-Degrading Strain Isolated from Wastewater.
Genome Announc
PUBLISHED: 08-10-2013
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Pseudomonas stutzeri strain B1SMN1 is a naphthalene-degrading and simultaneously nitrogen-fixing strain isolated from a wastewater sample taken at a lagooning treatment plant in Menorca (Balearic Islands, Spain). Here we report the draft genome sequence of P. stutzeri B1SMN1. It is composed of a chromosome of an estimated size of 5.2 Mb and two plasmids of 44,324 bp and 56,118 bp.
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Electropysiologic evaluation of the visual pathway in patients with multiple sclerosis.
J Clin Neurophysiol
PUBLISHED: 08-06-2013
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To evaluate the ability of visual evoked potentials and pattern electroretinograms (PERG) to detect subclinical axonal damage in patients during the early diagnostic stage of multiple sclerosis (MS). The authors also compared the ability of optical coherence tomography (OCT), PERG, and visual evoked potentials to detect axonal loss in MS patients and correlated the functional and structural properties of the retinal nerve fiber layer.
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Metabolic considerations of drugs in the treatment of allergic diseases.
Expert Opin Drug Metab Toxicol
PUBLISHED: 08-01-2013
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The clinical management of allergic diseases involves a number of drugs, most of which are extensively metabolized. This review aims to analyze the metabolism and the clinical implications of altered metabolism for these drugs.
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Accumulation of mitochondrial DNA deletions within dopaminergic neurons triggers neuroprotective mechanisms.
Brain
PUBLISHED: 07-26-2013
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Acquired alterations in mitochondrial DNA are believed to play a pathogenic role in Parkinsons disease. In particular, accumulation of mitochondrial DNA deletions has been observed in substantia nigra pars compacta dopaminergic neurons from patients with Parkinsons disease and aged individuals. Also, mutations in mitochondrial DNA polymerase gamma result in multiple mitochondrial DNA deletions that can be associated with levodopa-responsive parkinsonism and severe substantia nigra pars compacta dopaminergic neurodegeneration. However, whether mitochondrial DNA deletions play a causative role in the demise of dopaminergic neurons remains unknown. Here we assessed the potential pathogenic effects of mitochondrial DNA deletions on the dopaminergic nigrostriatal system by using mutant mice possessing a proofreading-deficient form of mitochondrial DNA polymerase gamma (POLGD257A), which results in a time-dependent accumulation of mitochondrial DNA deletions in several tissues, including the brain. In these animals, we assessed the occurrence of mitochondrial DNA deletions within individual substantia nigra pars compacta dopaminergic neurons, by laser capture microdissection and quantitative real-time polymerase chain reaction, and determined the potential deleterious effects of such mitochondrial DNA alterations on mitochondrial function and dopaminergic neuronal integrity, by cytochrome c oxidase histochemistry and quantitative morphology. Nigral dopaminergic neurons from POLGD257A mice accumulate mitochondrial DNA deletions to a similar extent (?40-60%) as patients with Parkinsons disease and aged individuals. Despite such high levels of mitochondrial DNA deletions, the majority of substantia nigra pars compacta dopaminergic neurons from these animals did not exhibit mitochondrial dysfunction or degeneration. Only a few individual substantia nigra pars compacta neurons appeared as cytochrome c oxidase-negative, which exhibited higher levels of mitochondrial DNA deletions than cytochrome c oxidase-positive cells (60.38±3.92% versus 45.18±2.83%). Survival of dopaminergic neurons in POLGD257A mice was associated with increased mitochondrial DNA copy number, enhanced mitochondrial cristae network, improved mitochondrial respiration, decreased exacerbation of mitochondria-derived reactive oxygen species, greater striatal dopamine levels and resistance to parkinsonian mitochondrial neurotoxins. These results indicate that primary accumulation of mitochondrial DNA deletions within substantia nigra pars compacta dopaminergic neurons, at an extent similar to that observed in patients with Parkinsons disease, do not kill dopaminergic neurons but trigger neuroprotective compensatory mechanisms at a mitochondrial level that may account for the high pathogenic threshold of mitochondrial DNA deletions in these cells.
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Effect of cataract surgery on optical coherence tomography measurements and repeatability in patients with non-insulin-dependent diabetes mellitus.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 07-18-2013
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To evaluate the effect of uncomplicated cataract phacoemulsification on macular and retinal nerve fiber layer (RNFL) thickness using two spectral-domain optical coherence tomography (OCT) instruments, Cirrus OCT and Spectralis OCT, in patients having non-insulin-dependent diabetes mellitus (NIDDM) without retinopathy, and to assess the reliability of the OCT measurements before and after cataract surgery.
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Amplatzer Amulet left atrial appendage occluder entrapment through mitral valve.
Can J Cardiol
PUBLISHED: 07-01-2013
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We report on a 77-year-old woman in whom percutaneous left atrial appendage (LAA) closure was performed. The patient had a left atrial myxoma resection 3 years previously, and 2 years later, she suffered a transient ischemic attack. Atrial fibrillation was detected and anticoagulation therapy was established. An episode of intracranial bleeding forced interruption of anticoagulation. Thus, percutaneous LAA closure with an Amplatzer Amulet LAA Occluder (St Jude Medical) was proposed. During the procedure, the LAA occluder migrated and became trapped in the mitral valve. Secondary massive mitral regurgitation and hemodynamic instability forced emergent cardiac surgery. Successful removal of the Amplatzer Amulet LAA Occluder was achieved.
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Distribution of Retinal Layer Atrophy in Patients With Parkinson Disease and Association With Disease Severity and Duration.
Am. J. Ophthalmol.
PUBLISHED: 06-19-2013
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To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity.
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Retinal Layer Segmentation in Patients with Multiple Sclerosis Using Spectral Domain Optical Coherence Tomography.
Ophthalmology
PUBLISHED: 06-15-2013
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To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS.
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Genetic diversity of clinical Pseudomonas aeruginosa isolates in a public hospital in Spain.
BMC Microbiol.
PUBLISHED: 06-13-2013
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Pseudomonas aeruginosa is an important nosocomial pathogen that exhibits multiple resistances to antibiotics with increasing frequency, making patient treatment more difficult. The aim of the study is to ascertain the population structure of this clinical pathogen in the Hospital Son Llàtzer, Spain.
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Pseudomonas aestusnigri sp. nov., isolated from crude oil-contaminated intertidal sand samples after the Prestige oil spill.
Syst. Appl. Microbiol.
PUBLISHED: 06-11-2013
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Strains VGXO14(T) and Vi1 were isolated from the Atlantic intertidal shore from Galicia, Spain, after the Prestige oil spill. Both strains were Gram-negative rod-shaped bacteria with one polar inserted flagellum, strictly aerobic, and able to grow at 18-37°C, pH 6-10 and 2-10% NaCl. A preliminary analysis of the 16S rRNA and the partial rpoD gene sequences indicated that these strains belonged to the Pseudomonas genus but were distinct from any known Pseudomonas species. A polyphasic taxonomic approach including phylogenetic, chemotaxonomic, phenotypic and genotypic data confirmed that the strains belonged to the Pseudomonas pertucinogena group. In a multilocus sequence analysis, the similarity of VGXO14(T) and Vi1 to the closest type strain of the group, Pseudomonas pachastrellae, was 90.4%, which was lower than the threshold of 97% established to discriminate species in the Pseudomonas genus. The DNA-DNA hybridisation similarity between strains VGXO14(T) and Vi1 was 79.6%, but below 70% with the type strains in the P. pertucinogena group. Therefore, the strains should be classified within the genus Pseudomonas as a novel species, for which the name Pseudomonas aestusnigri is proposed. The type strain is VGXO14(T) (=CCUG 64165(T)=CECT 8317(T)).
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Neuro-ophthalmologic evaluation, quality of life, and functional disability in patients with MS.
Neurology
PUBLISHED: 05-24-2013
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To evaluate correlations between longitudinal changes in neuro-ophthalmologic measures and quality of life (QOL) and disability in patients with multiple sclerosis (MS), using optical coherence tomography (OCT), visual evoked potentials (VEP), and visual field examination.
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Neural networks to identify multiple sclerosis with optical coherence tomography.
Acta Ophthalmol
PUBLISHED: 05-07-2013
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Purpose:  To compare axonal loss in ganglion cells detected with spectral-domain optical coherence tomography (OCT) in eyes of patients with multiple sclerosis (MS) versus healthy control subjects using an artificial neural network (ANN). To analyse the capability of the ANN technique to improve the detection of retinal nerve fibre layer (RNFL) damage in patients with multiple sclerosis. Methods:  Patients with multiple sclerosis (n?=?106) and age-matched healthy subjects (n?=?115) were enrolled. The Spectralis OCT system was used to obtain the circumpapillary RNFL thickness in both eyes. The 768 RNFL thickness measurements provided by the Spectralis OCT were performed to obtain thickness measurements from 24 uniformly divided locations around the peripapillary RNFL. The performance of the ANN technique for identifying RNFL loss in patients with multiple sclerosis was evaluated. Receiver-operating characteristic (ROC) curves were used to display the ability of the test to discriminate between MS and healthy eyes in our population. ROC curves obtained using ANN and parameters provided by OCT (mean and 6 sector thicknesses) were compared. Results:  The capability of the ANN technique to detect RNFL loss in patients with multiple sclerosis compared with healthy subjects was good. The area under the ROC curve was 0.945. Compared with the OCT-provided parameters, the ANN had the largest area under the ROC curve. Conclusions:  Measurements of RNFL thickness obtained with Spectralis OCT have a good ability to differentiate between healthy and individuals with multiple sclerosis. Based on the area under the ROC curve, the ANN performed better than any single OCT parameter.
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Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice.
Exp. Physiol.
PUBLISHED: 04-26-2013
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What is the central question of this study? We explored whether experimental cancer-induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles,and whether signalling pathways, proteasome and oxidative stress influence that process. What is the main finding and what is its importance? In cancer cachectic mice, MRC complexes and oxygen consumption were decreased in the diaphragm and gastrocnemius. Blockade of nuclear factor-?B and mitogen-activated protein kinase actions partly restored the muscle mass and force and corrected the MRC dysfunction,while concomitantly reducing tumour burden. Antioxidants improved mitochondrial oxygen consumption without eliciting effects on the loss of muscle mass and force or the tumour size,whereas bortezomib reduced tumour burden without influencing muscle mass and strength or MRC function. Abnormalities in mitochondrial content, morphology and function have been reported in several muscle-wasting conditions. We specifically explored whether experimental cancer-induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles, and whether signalling pathways, proteasomes and oxidative stress may influence that process. We evaluated complex I, II and IV enzyme activities (specific activity assays) and MRC oxygen consumption (polarographic measurements) in diaphragm and gastrocnemius of cachectic mice bearing the LP07 lung tumour, with and without treatment with N-acetylcysteine, bortezomib and nuclear factor-?B (sulfasalazine) and mitogen-activated protein kinases (MAPK, U0126) inhibitors (n = 10 per group for all groups). Whole-body and muscle weights and limb muscle force were also assessed in all rodents at baseline and after 1 month. Compared with control animals, cancer cachectic mice showed a significant reduction in body weight gain, smaller sizes of the diaphragm and gastrocnemius, lower muscle strength, decreased activity of complexes I, II and IV and decreased oxygen consumption in both muscles. Blockade of nuclear factor-?B and MAPK actions restored muscle mass and force and corrected the MRC dysfunction in both muscles, while partly reducing tumour burden. Antioxidants improved mitochondrial oxygen uptake without eliciting significant effects on the loss of muscle mass and force or tumour size, whereas the proteasome inhibitor reduced tumour burden without significantly influencing muscle mass and strength or mitochondrial function. In conclusion, nuclear factor-?B and MAPK signalling pathways modulate muscle mass and performance and MRC function of respiratory and limb muscles in this model of experimental cancer cachexia, thus offering targets for therapeutic intervention.
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Role of color Doppler imaging in early diagnosis and prediction of progression in glaucoma.
Biomed Res Int
PUBLISHED: 04-22-2013
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This longitudinal and prospective study analyzes the ability of orbital blood flow measured by color Doppler imaging (CDI) to predict glaucoma progression in patients with glaucoma risk factors. Patients with normal perimetry but having glaucoma risk factors and patients in the initial phase of glaucoma were prospectively included in the study and divided, after a five-year follow-up, into two groups: "Progression" and "No Progression" based on the changes in the Moorfields regression analysis (MRA) classification of Heidelberg retina tomograph (HRT). An orbital CDI was performed in all patients and the parameters obtained were correlated with changes in HRT. A logistic discrimination function (LDF) was calculated for ophthalmic artery (OA) and central retinal artery (CRA) parameters. Receiver operating characteristics curves (ROC) were used to assess the usefulness of LDFs to predict glaucomatous progression. A total of 71 eyes were included. End-diastolic velocity, time-averaged velocity, and resistive index in the OA and CRA were significantly different (P < 0.05) between the Progression and No Progression groups. The area under the ROC curves calculated for both LDFs was of 0.695 (OA) and 0.624 (CRA). More studies are needed to evaluate the ability of CDI to perform early diagnosis and to predict progression in glaucoma in eyes.
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Anti-Parkinsons disease drugs and pharmacogenetic considerations.
Expert Opin Drug Metab Toxicol
PUBLISHED: 04-09-2013
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The development of pharmacogenetic-based clinical practice guidelines for the use of anti-Parkinsons disease drugs requires, as a pre-requisite, the identification and validation of genetic biomarkers. These biomarkers are then used as surrogate endpoints. This review analyzes potential genetic biomarkers which can be used to improve anti-Parkinsons disease therapy.
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Genes involved in hemorrhagic transformations that follow recombinant t-PA treatment in stroke patients.
Pharmacogenomics
PUBLISHED: 04-06-2013
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Despite the benefits of recombinant t-PA (rt-PA) for stroke patients some of them suffer from adverse hemorrhagic transformations (HTs) following treatment. Our objective is to study the transcriptomics of HTs patients.
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LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis.
BMC Neurol
PUBLISHED: 04-03-2013
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Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent.
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Reproducibility and repeatability of Cirrus and Spectralis Fourier-domain optical coherence tomography of healthy and epiretinal membrane eyes.
Retina (Philadelphia, Pa.)
PUBLISHED: 03-30-2013
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To evaluate the accuracy and reproducibility of retinal thickness measurements in healthy and epiretinal membranes (ERM) eyes by Cirrus and Spectralis Fourier-domain optical coherence tomography devices.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.