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Find video protocols related to scientific articles indexed in Pubmed.
LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity.
Hum. Mol. Genet.
PUBLISHED: 07-30-2014
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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD), and sequence variations at the LRRK2 locus are associated with increased risk for sporadic PD. LRRK2 contains both GTPase and kinase domains flanked by protein interaction motifs, and mutations associated with familial PD have been described for both catalytic domains. LRRK2 has been implicated in diverse cellular processes, and recent evidence pinpoints to an important role for LRRK2 in modulating a variety of intracellular membrane trafficking pathways. However, the underlying mechanisms are poorly understood. Here, by studying the classical, well-understood, degradative trafficking pathway of the epidermal growth factor receptor (EGFR), we show that LRRK2 regulates endocytic membrane trafficking in an Rab7-dependent manner. Mutant LRRK2 expression causes a slight delay in early-to-late endosomal trafficking, and a pronounced delay in trafficking out of late endosomes, which become aberrantly elongated into tubules. This is accompanied by a delay in EGFR degradation. The LRRK2-mediated deficits in EGFR trafficking and degradation can be reverted upon coexpression of active Rab7 and of a series of proteins involved in bridging the EGFR to Rab7 on late endosomes. Effector pulldown assays indicate that pathogenic LRRK2 decreases Rab7 activity both in cells overexpressing LRRK2, as well as in fibroblasts from pathogenic mutant LRRK2 PD patients when compared with healthy controls. Together, these findings provide novel insights into a previously unknown regulation of Rab7 activity by mutant LRRK2 which impairs membrane trafficking at very late stages of the endocytic pathway.
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A cut-point value of uncarboxylated to carboxylated index is associated with glycemic status markers in type 2 diabetes.
J. Investig. Med.
PUBLISHED: 07-16-2014
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The uncarboxylated osteocalcin (ucOC) has been described as a regulator of glucose metabolism in mice, and it is decreased in human type 2 diabetes mellitus (T2D). Although inversely correlated with serum glucose, insulin, and glycated hemoglobin, it is unclear if ucOC decrement is caused by diabetes or plays a role in the pathogenesis and/or progression of the disease. Whatever the case may be, diabetes affects osteoblast gene expression, and possibly the proportion of ucOC over carboxylated OC (cOC). The association of ucOC/cOC index with glycemic status markers in patients with T2D has not been described before.
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Associations between arsenic species in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico.
Environ. Health Perspect.
PUBLISHED: 06-26-2014
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A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals.
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Tailored nutrition education and food assistance improve adherence to HIV antiretroviral therapy: evidence from Honduras.
AIDS Behav
PUBLISHED: 05-03-2014
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Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.
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Novel insights into the neurobiology underlying LRRK2-linked Parkinson's disease.
Neuropharmacology
PUBLISHED: 01-19-2014
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Mutations in LRRK2 (leucine-rich repeat kinase 2) are found associated with both sporadic and familial Parkinson's disease (PD). Pathogenic mutations are localized to the catalytic domains of LRRK2, including kinase and GTPase domains. Altered catalytic activity correlates with neurotoxicity, indicating that targeting those activities may provide clues as to novel therapeutic strategies for LRRK2-linked PD. However, the cellular readout of such altered catalytic activities remains largely unknown. Recent cell biological studies have started to highlight possible early cellular events which are altered in the presence of pathogenic LRRK2 and may ultimately lead to neuronal demise, and these studies link altered LRRK2 function to various abnormal endolysosomal vesicular trafficking events. This review examines our current knowledge of LRRK2 neurobiology and how pathogenic mutations may lead to neurodegeneration in PD.
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Placental maturity, hypertensive disorders of pregnancy and birth weight.
Hypertens Pregnancy
PUBLISHED: 12-04-2013
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Objectives: To compare maturity of placentas from women with hypertensive disorders with those from normotensive pregnancies and to determine the relationship between placental maturity (PM) and the diagnosis of small-for-gestational-age (SGA) in the newborns. Materials and methods: We examined placental stained specimens from women with normotensive pregnancies (n?=?100), diagnosis of gestational hypertension (n?=?38), mild (n?=?10), or severe preeclampsia (n?=?34) in an optical microscope. Placental Maturity Index (PMI) was calculated as the number of vasculo-syncytial membranes (VSM) in 1?mm(2) divided by VSM thickness (µm). Hypermaturity was defined as >90th percentile of the PMI from placentas of normotensive pregnancies. Newborns were classified as SGA, adequate-for-gestational-age (AGA) or large-for-gestational-age (<10th, 10-90th, and >90th percentile from weight for gestational age reference tables, respectively). Results: PMI in preeclamptic women (taking together mild and severe preeclampsia, PMI?=?43.4?±?1.6) was significantly higher than in normotensive women (PMI?=?36?±?2, p?=?0.045). Hypermaturity was more frequent (p?
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A direct interaction between Leucine-rich Repeat Kinase 2 and specific ?-tubulin isoforms regulates tubulin acetylation.
J. Biol. Chem.
PUBLISHED: 11-25-2013
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Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2, are a common cause of Parkinsons disease. LRRK2 has been suggested to influence the cytoskeleton as LRRK2 mutants reduce neurite outgrowth and cause an accumulation of hyperphosphorylated tau. This might cause alterations in the dynamic instability of microtubules suggested to contribute to the pathogenesis of Parkinsons disease. Here, we describe a direct interaction between LRRK2 and ?-tubulin. This interaction is conferred by the LRRK2 Roc domain and is disrupted by the familial R1441G mutation and artificial Roc domain mutations that mimic autophosphorylation. LRRK2 selectively interacts with three ?-tubulin isoforms: TUBB, TUBB4 and TUBB6, one of which (TUBB4) is mutated in the movement disorder dystonia type 4 (DYT4). Binding specificity is determined by lysine-362 and alanine-364 of ?-tubulin. Molecular modelling was used to map the interaction surface to the luminal face of microtubule protofibrils in close proximity to the lysine-40 acetylation site in ?-tubulin. This location is predicted to be poorly accessible within mature stabilized microtubules, but exposed in dynamic microtubule populations. Consistent with this finding, endogenous LRRK2 displays a preferential localization to dynamic microtubules within growth cones, rather than adjacent axonal microtubule bundles. This interaction is functionally relevant to microtubule dynamics, as mouse embryonic fibroblasts derived from LRRK2 knockout mice display increased microtubule acetylation. Taken together, our data shed light on the nature of the LRRK2-tubulin interaction, and indicate that alterations in microtubule stability caused by changes in LRRK2 might contribute to the pathogenesis of Parkinsons disease.
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Regional vulnerability of hippocampal subfields and memory deficits in Parkinsons disease.
Hippocampus
PUBLISHED: 03-29-2013
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Neuropathological studies show the hippocampus is affected in Parkinsons disease (PD), with the second subfield of the cornu armonis (CA2) being the most involved. Our aims were to assess in vivo volumes of different hippocampal subfields in patients with PD with and without visual hallucinations using MRI and test their association with verbal learning and long-term recall. A total of 18 nondemented PD patients, 18 nondemented PD patients with visual hallucinations and 18 neurologically unimpaired elderly controls matched by age and gender were enrolled in this study. We assessed the volumes of seven hippocampal subfields on MRI, including the cornu armonis (CA) sectors, subiculum, presubiculum, and the dentate gyrus (DG) using a novel technique that enables automated volumetry. The CA2-3 and CA4-DG subfields were significantly smaller in both groups of patients, while the subiculum was only reduced in PD patients with visual hallucinations, compared to controls. Significant correlations were found between learning performance and CA2-3 as well as CA4-DG volumes in the whole patient sample. These data show there is regional atrophy of specific hippocampal subfields in PD, which is more severe and further extends to the subiculum in patients with visual hallucinations. Our findings indicate that learning deficits are associated with volume loss in subfields that act as input regions in the hippocampal circuit, suggesting that degeneration in these regions could be responsible for cognitive dysfunction in PD.
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Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.
Chem. Res. Toxicol.
PUBLISHED: 12-21-2011
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Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and ?-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an automated workflow as a simple, sensitive, and time and money saving procedure for rapid identification of the GST-T1 and GST-M1 positive or null genotypes.
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Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function.
Alcohol. Clin. Exp. Res.
PUBLISHED: 09-06-2011
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Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico.
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[A clinical guideline for diagnosis and treatment of hydrocele in childhood].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 04-26-2011
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To develop a guideline available to the medical staff of the first and second level of care, which includes recommendations based on the best available evidence about diagnosis and management of hydrocele in the pediatric patient.
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Cytotoxicity of functionalized carbon nanotubes in J774A macrophages.
Nanomedicine
PUBLISHED: 04-06-2011
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Cytotoxicity of carbon nanotubes (CNTs) is a prime concern for its use as antigen carriers. Here we evaluated the cytotoxic effect of unpurified (UP-CNTs), purified (P-CNTs), fluorescein isothiocyanate-functionalized (FITC-CNTs), and Entamoeba histolytica 220-kDa lectin-functionalized CNTs (L220-CNTs) in J774A macrophage (MOs) cell line. Cell viability and apoptosis were analyzed by MTT and TUNEL assays, respectively. Cyclooxygenase-2 (COX-2) was analyzed by reverse transcription-polymerase chain reaction. Cytotoxicity at 6.0 mg/L was higher with UP-CNTs > P-CNTs > FITC-CNTs, showing a decrease in cell viability and an increase in apoptosis. In contrast, MOs interacted with L220-CNTs showed an increase in cell viability without signs of apoptosis. Although UP-CNTs and P-CNTs exhibited COX-2 induction with 6.0 mg/L, functionalized CNTs were able to induce COX-2 at concentrations as low as 0.06 mg/L. These results suggest that functionalization decreases toxicity, and that L220-CNTs may be an excellent candidate for the production of a nanovaccine against amebiasis.
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[Glycosylated haemoglobin A1c compared to fasting plasma glucose in outpatients referred to a medical laboratory].
Rev Salud Publica (Bogota)
PUBLISHED: 02-23-2011
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Comparing haemoglobin A glycosylate (HbA1c) at different cutoff points for blood glucose measurement to the fasting plasma glucose (FPG) test in outpatients visiting a medical laboratory in the city of Medellin between March and April 2010.
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Production of first generation adenoviral vectors for preclinical protocols: amplification, purification and functional titration.
J. Biosci. Bioeng.
PUBLISHED: 01-07-2011
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Gene therapy represents a promising approach in the treatment of several diseases. Currently, the ideal vector has yet to be designed; though, adenoviral vectors (Ad-v) have provided the most utilized tool for gene transfer due principally to their simple production, among other specific characteristics. Ad-v viability represents a critical variable that may be affected by storage or shipping conditions and therefore it is advisable to be assessed previously to protocol performance. The present work is unique in this matter, as the complete detailed process to obtain Ad-v of preclinical grade is explained. Amplification in permissive HEK-293 cells, purification in CsCl gradients in a period of 10 h, spectrophotometric titration of viral particles (VP) and titration of infectious units (IU), yielding batches of Ad?Gal, AdGFP, AdHuPA and AdMMP8, of approximately 10¹³-10¹? VP and 10¹²-10¹³ IU were carried out. In vivo functionality of therapeutic AdHuPA and AdMMP8 was evidenced in rats presenting CCl?-induced fibrosis, as more than 60% of fibrosis was eliminated in livers after systemic delivery through iliac vein in comparison with irrelevant Ad?Gal. Time required to accomplish the whole Ad-v production steps, including IU titration was 20 to 30 days. We conclude that production of Ad-v following standard operating procedures assuring vector functionality and the possibility to effectively evaluate experimental gene therapy results, leaving aside the use of high-cost commercial kits or sophisticated instrumentation, can be performed in a conventional laboratory of cell culture.
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The functional class evaluated in rheumatoid arthritis is associated with soluble TGF-?1 serum levels but not with G915C (Arg25Pro) TGF-?1 polymorphism.
Rheumatol. Int.
PUBLISHED: 07-29-2010
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The influence of genetic factors in rheumatoid arthritis (RA) has been described, including several cytokine genes such as transforming growth factor ? (TGF-?) with regulatory effects on lymphocytes, dendritic cells, macrophages, chondrocytes, and osteoblasts, which are important in the RA pathogenesis. The G915C TGF-?1 polymorphism has been associated with soluble TGF-?1 (sTGF-?) serum levels. Thus, we studied the association of G915C (Arg25Pro) TGF-?1 polymorphism with sTGF-?1 serum levels in RA. We enrolled 120 RA patients and 120 control subjects (CS). The G915C TGF-?1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and sTGF-?1 serum levels were quantified using an ELISA kit. The genotype frequency of G915C TGF-?1 polymorphism in RA and CS was G/G (91.7%), G/C (8.3%), C/C (0%) and G/G (85.8%), G/C (14.2%), C/C (0%), respectively, without significant differences. Moreover, the G/G TGF-?1 genotype carriers presented the highest disability index evaluated for the Spanish HAQ-DI score (P < 0.001). In addition, the sTGF-?1 serum levels were higher in RA (182.2 ng/mL) than CS (160.2 ng/mL), there was not significant difference. However, we found a positive correlation between the sTGF-?1 serum levels and the functional class (r = 0.472, P = 0.023). In conclusion, the G915C (Arg25Pro) TGF-?1 polymorphism is not associated with RA, but the sTGF-?1 serum levels are related with the functional class in RA.
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Evolution of the crashworthiness and aggressivity of the Spanish car fleet.
Accid Anal Prev
PUBLISHED: 03-18-2010
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This paper investigates the relationship between a passenger cars year of registration and its crashworthiness and aggressivity in real-world crashes. Crashworthiness is defined as the ability of a car to protect its own occupants, and has been evaluated in single and two-car crashes. Aggressivity is defined as the ability to protect users travelling in other vehicles, and has been evaluated only in two-car crashes. The dependent variable is defined as the proportion of injured drivers who are killed or seriously injured; following previous research, we refer to this magnitude as injury severity. A decrease in the injury severity of a driver is interpreted as an improvement in the crashworthiness of their car; similarly, a decrease in the injury severity of the opponent driver is regarded as an improvement in aggressivity. Data have been extracted from the Spanish Road Accident Database, which contains information on every accident registered by the police in which at least one person was injured. Two types of regression models have been used: logistic regression models in single-car crashes, and generalised estimating equations (GEE) models in two-car crashes. GEE allow to take account of the correlation between the injury severities of drivers involved in the same crash. The independent variables considered have been: year of registration of the subject car (crashworthiness component), year of registration of the opponent car (aggressivity component), and several factors related to road, driver and environment. Our models confirm that crashworthiness has largely improved in two-car crashes: when crashing into the average opponent car, drivers of cars registered before 1985 have a significantly higher probability of being killed or seriously injured than drivers of cars registered in 2000-2005 (odds ratio: 1.80; 95% confidence interval: 1.61; 2.01). In single-car crashes, the improvement in crashworthiness is very slight (odds ratio: 1.04; 95% confidence interval: 0.93; 1.16). On the other hand, we have also found a significant worsening in aggressivity in two-car crashes: the driver of the average car has a significantly lower probability of being killed or seriously injured when crashing into a car registered before 1985, than when crashing into a car registered in 2000-2005 (odds ratio: 0.52; 95% confidence interval: 0.45; 0.60). Our results are consistent with a large amount of previous research that has reported significant improvements in the protection of car occupants. They also add to some recent studies that have found a worsening in the aggressivity of modern cars. This trend may be reflecting the impact of differences in masses and travel speeds, as well as the influence of consumer choices. The precise reasons have to be investigated. Also, the causes have to be found for so large a discrepancy between crashworthiness in single and two-car crashes.
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A reliable method of liquid chromatography for the quantification of acetaminophen and identification of its toxic metabolite N-acetyl-p-benzoquinoneimine for application in pediatric studies.
Biomed. Chromatogr.
PUBLISHED: 03-10-2010
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The aim of the present study was to develop a simple, selective and reliable method to quantify acetaminophen and its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) for pediatric studies using 100?µL plasma samples, by reverse-phase HPLC and UV detection. The assay was performed using a C?? column and an isocratic elution with water-methanol-formic acid (70:30:0.15; v/v/v) as mobile phase. Linearity of the method was assayed in the range of 1-30?µg/mL for acetaminophen and 10-200 µg/mL for NAPQI, with a correlation coefficient r?=?0.999 for both compounds, and inter- and intra-day coefficients of variation of less than 13%. Several commonly co-administered drugs were analyzed for selectivity and no interference with the determinations was observed. The detection and quantification limits for acetaminophen and NAPQI were 0.1 and 1?µg/mL, and 0.1 and 10?µg/mL respectively. The present method can be used to monitor acetaminophen levels using 100 µL plasma samples, which may be helpful when very small samples need to be analyzed, as in pharmacokinetics determination or drug monitoring in plasma in children. This assay is also able to detect the NAPQI for drug monitoring in patients diagnosed with acetaminophen intoxication.
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Frontal and associative visual areas related to visual hallucinations in dementia with Lewy bodies and Parkinsons disease with dementia.
Mov. Disord.
PUBLISHED: 02-23-2010
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Visual Hallucinations (VH) are among the core features of Dementia with Lewy Bodies (DLB), but are also very frequent in demented patients with Parkinsons Disease (PDD). The purpose of this study was to investigate the pattern of gray matter and cognitive impairment underlying VH in DLB and PDD. We applied voxel-based morphometry and behavioral assessment to 12 clinically diagnosed DLB patients and 15 PDD patients. Subjects with VH showed greater gray matter loss than non-hallucinators, specifically in the right inferior frontal gyrus (BA 45) in the DLB patients and in the left orbitofrontal lobe (BA 10) in the PDD patients. Comparing the two subgroups with VH, DLB patients had greater decrease of the bilateral premotor area (BA 6) than PDD patients. Furthermore, decreased volume in associative visual areas, namely left precuneus and inferior frontal lobe, correlated with VH in the DLB but not in PDD patients. VH were related to impaired verbal fluency, inhibitory control of attention and visuoperception in the DLB group and to visual memory in the PDD group. In conclusion, DLB and PDD patients with VH had more frontal gray matter atrophy than non-hallucinators, the impairment being greater in the DLB group. The patterns of structural and functional correlations were different in both pathologies.
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Differential progression of brain atrophy in Parkinsons disease with and without visual hallucinations.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 12-03-2009
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To determine the course of cognitive deficits and the regional progression of brain atrophy in patients with Parkinsons disease (PD) with and without visual hallucinations (VH).
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Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population: unusual high frequency of CYP2E1*c2 allele.
Alcohol. Clin. Exp. Res.
PUBLISHED: 10-23-2009
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Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out.
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Effects of exposure to pesticides during pregnancy on placental maturity and weight of newborns: a cross-sectional pilot study in women from the Chihuahua State, Mexico.
Hum Exp Toxicol
PUBLISHED: 09-10-2009
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It is known that pesticides cross the placental barrier and can cause alterations in the development of placental structures resulting in adverse effects in reproduction. The objectives of this study were to investigate the effects of pesticide exposure during pregnancy on placental maturity and to evaluate the relationship between placental maturity, gestational age and birth weight. We collected the placentas from singleton pregnancies from women exposed (n = 9) and non-exposed (n = 45 full-term and n = 31 preterm) to pesticides as evaluated geographically, by questionnaire and by acetylcholinesterase levels. Placental morphometry from the central and peripheral regions was examined by microscopy and staining with hematoxylin and eosin. The placental maturity index (PMI) was estimated by dividing the number of epithelial plates in terminal villi to their thickness in 1 mm(2) of the placental parenchyma. Gestational age, birth weight and the following characteristics of the mother were also recorded: pre-pregnancy body mass index, weight gain during pregnancy and hemoglobin concentrations. Birth weight and the gestational age were correlated with PMI (r = .54 and r = .44, respectively; p < .01). Pesticide exposure was associated with a higher PMI (beta = 7.38, p = .01) after adjusting by variables related to placental maturity. In conclusion, the results suggest a relationship between prenatal exposure to pesticides and placental maturity and may potentially affect the nutrient transport from the mother to the fetus.
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[Expression of muscarinic cholinergic receptors in human term placenta].
Ginecol Obstet Mex
PUBLISHED: 08-18-2009
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Studies in the human term placenta have shown that muscarinic cholinergic receptors M1-M4 are located in the sincitiotrofoblasto in the basement membrane and in the brush border membrane of the villi. However, in both studies the methodology has not been implicated microscopy methods to reveal its location.
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Correlations between gray matter reductions and cognitive deficits in dementia with Lewy Bodies and Parkinsons disease with dementia.
Mov. Disord.
PUBLISHED: 07-02-2009
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There is controversy regarding whether Dementia with Lewy Bodies (DLB) and Parkinsons disease with dementia (PDD) may or not be different manifestations of the same disorder. The purpose of the present study was to investigate possible correlations between brain structure and neuropsychological functions in clinically diagnosed patients with DLB and PDD. The study sample consisted of 12 consecutively referred DLB patients, 16 PDD patients, and 16 healthy control subjects recruited from an outpatient setting, who underwent MRI and neuropsychological assessment. Voxel-based morphometry results showed that DLB patients had greater gray matter atrophy in the right superior frontal gyrus, the right premotor area and the right inferior frontal lobe compared to PDD. Furthermore, the anterior cingulate and prefrontal volume correlated with performance on the Continuous Performance Test while the right hippocampus and amygdala volume correlated with Visual Memory Test in the DLB group. In conclusion, DLB patients had more fronto-temporal gray matter atrophy than PDD patients and these reductions correlated with neuropsychological impairment.
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Neuroanatomical substrate of visuospatial and visuoperceptual impairment in Parkinsons disease.
Mov. Disord.
PUBLISHED: 05-05-2009
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To determine magnetic resonance imaging patterns of gray matter (GM) atrophy underlying visuospatial and visuoperceptual impairment in Parkinsons disease (PD), we applied voxel-based morphometry to 36 nondemented PD patients and correlated their whole brain GM density with performance on three visuospatial and visuoperceptual tests. In addition, group comparisons between patients and 20 healthy controls were also performed. Correlations between visuospatial performance and GM density were found in the superior parietal lobules and the superior occipital gyrus of PD patients. Poor performance on visuoperceptual tests was also found to be significantly associated with GM decreases in the fusiform, the parahippocampus, and the middle occipital gyrus. Finally, group comparisons between controls and patients showed widespread GM cortical reductions in PD, involving posterior temporal and parietal regions. Taken together, these findings suggest that visuospatial and visuoperceptual dysfunctions reflect structural GM changes in temporo-parietal cortical regions of PD patients.
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Comparative bioavailability of propafenone after administration of a magistral suspension vs. commercial tablets in healthy volunteers.
Arzneimittelforschung
PUBLISHED: 05-01-2009
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Propafenone (CAS 34183-22-7) is an effective antiarrhythmic drug used in children, although in some countries no specific pediatric formulation is available. The aim of this study is to compare the relative bioavailability of a magistral (MAG) preparation of propafenone versus its commercial (COM) presentation in a group of 16 Mexican healthy volunteers. Bioavailability was determined after crossover administration of the drugs, through a randomized two-phase trial. All volunteers had normal hepatic and renal functions, determined clinically at the beginning of the study, and received 150 mg of either COM (tablets) or MAG (suspension). Blood samples were drawn for a 24-h post-dose analysis by HPLC to measure plasma levels of propafenone. Subjects (mean 25.9 +/- 5.3 years and 66.1 +/- 12.4 kg) had the following pharmacokinetic parameters: Cmax 189.9 +/- 20.92 ng/mL, Tmax 1.5 h, AUC 322.4 +/- 36.28 ng x ml(-1) x h for COM. Values for MAG were Cmax 225.8 +/- 24.38 ng/mL, Tmax 1.7 h and AUC 359.3 +/- 27.90 ng x ml(-1) x h. These values yielded a relative bioavailability of 111.42% for MAG compared with COM. No electrocardiographic changes were recorded in any subject with respect to the baseline value, in both treatment schemes. Therefore, propafenone suspension prepared as a magistral formulation may be used as an alternative drug in pediatric patients.
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Structural brain correlates of verbal fluency in Parkinsons disease.
Neuroreport
PUBLISHED: 04-08-2009
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Verbal fluency tests are often used to assess cognitive dysfunction in Parkinsons disease. These tests have been found to be impaired even in initial stages of this illness. We applied voxel-based morphometry to investigate the neuroanatomic substrates of semantic and phonemic fluency impairment. Correlations between gray matter density and semantic as well as phonemic fluency performance were performed in 32 nondemented Parkinsons disease patients. We found that gray matter of temporal, frontal and cerebellar areas correlated with semantic fluency scores. In contrast, no gray matter correlations were found for phonemic fluency or for general cognitive functions. These results suggest that semantic fluency impairment is reflecting structural gray matter changes in regions involved in language networks.
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[Dental fluorosis in 6-13-year-old children attending public schools in Medellín, Colombia].
Rev Salud Publica (Bogota)
PUBLISHED: 01-19-2009
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This study was aimed at determining dental fluorosis prevalence and severity amongst 6-13-year-old students residing in Medellin, Colombia.
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Establishment of a cut-point value of serum TNF-alpha levels in the metabolic syndrome.
J. Clin. Lab. Anal.
PUBLISHED: 01-14-2009
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Cardiovascular diseases and type 2 diabetes are the major causes of mortality in Mexico. Metabolic syndrome (MS) is a cluster of factors that increase the risk to develop such diseases. Previous studies have shown that MS is associated with high tumor necrosis factor (TNF-alpha) levels. In fact, TNF-alpha has been proposed to be a useful marker for clinical diagnosis of inflammation at an early stage. Therefore, we analyzed TNF-alpha concentrations in Mexican individuals with or without MS and related these levels to the associated MS components. Clinical, anthropometric, and biochemical data were analyzed in 41 healthy and 39 MS individuals. Individuals were similarly grouped by age and gender.The serum TNF-alpha levels measured by a highly sensitive enzyme-linked immunosorbent assay (ELISA) kit were increased significantly in MS subjects compared with healthy individuals (P<0.001). The assay showed 78.1% sensitivity and 61.5% specificity with a cut-point level of 1.36 pg/mL. TNF-alpha levels higher than the cut-point value were correlated with insulin resistance indices. These findings support the hypothesis that serum TNF-alpha concentration could be a useful marker for early MS diagnosis. Nevertheless, we suggest the establishment of specific cut-point values in each studied population to evaluate potential clinical applications.
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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.