DQB1*0602 confers genetic susceptibility to multiple sclerosis in Afro-Brazilians

We studied the distribution of the HLA-DRB1, -DQA1 and -DQB1 alleles in 44 Afro-Brazilian patients with multiple sclerosis and 88 controls. Although no significant differences were found between the patients and controls for the DRB1 and DQA1 alleles, the HLA-DQB1*0602 allele was positively associated with multiple sclerosis (45.0% vs. 17.0%, Pc=0.024, RR=3.31). The positive extended haplotypes for DQB1*0602 were more frequent in patients than controls, although the differences were not statistically significant in any of them. These results in Afro-Brazilians are in line with other studies which have found DQB1*0602 to be associated with the disease in the absence of the DRB1*1501 allele. We therefore think that the association with the disease in this ethnic group is more allelic than haplotypic.     

Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.     

Hemostatic coronary risk factors in a healthy population of Maracaibo,Venezuela

The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.     

Drosophila dSAP18 is a nuclear protein that associates with chromosomes and the nuclear matrix, and interacts with pinin, a protein factor involved in RNA splicing

SAP18 is a highly conserved protein that was proposed to be involved in multiple cellular processes from autophagy to gene regulation and mRNA processing. In this paper we show that, in Drosophila, dSAP18 is a predominantly nuclear protein that associates to both chromosomes and the nuclear matrix. dSAP18 becomes nuclear early during development, at the onset of cellularization, and remains so all through embryo development. dSAP18 is also nuclear in salivary glands, ovaries and cultured S2 cells. Here we also show that dSAP18 forms a complex with the Drosophila homolog of pinin (dPnn), a protein factor involved in mRNA splicing. dSAP18-dPnn interaction was confirmed in vivo, through co-immunoprecipitation experiments, as well as in vitro, through GST pull-down assays. These results are discussed in the context of the possible functions played by SAP18.     

Beta-alanine potentiation of [3H]flunitrazepam binding to rat spinal cord homogenates

The effect of beta-alanine, gamma-aminobutyric acid (GABA), and other functionally related amino acids on [3H]flunitrazepam binding to rat spinal cord homogenates was studied. beta-Alanine potentiated [3H]flunitrazepam binding by 40% and GABA by 88%. Taurine increased the binding by 19%. Hypotaurine produced an 11% increase. No significant effect was seen in glycine, alanine, serine, valine or the dipeptide carnosine. The beta-alanine increase in [3H]flunitrazepam binding was completely inhibited by 10 microM strychnine, whereas the GABA increase required 0.1 mM strychnine to be fully suppressed. Results suggest that beta-alanine specifically potentiates binding of [3H]flunitrazepam in rat spinal cord homogenates.     

Effects of overexpansion on stents' recoil, symmetry/asymmetry, and neointimal hyperplasia in aortas of hypercholesterolemic rabbits.

BACKGROUND: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. OBJECTIVES: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. METHODS: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. RESULTS: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28+/-0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10+/-0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. CONCLUSIONS: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion.     

Postnatal naltrindole treatments induce behavioural modifications in preweanling rats

To investigate the physiological role of the delta-opioid receptor during the preweanling period, we have studied the effects of chronic (daily injections from birth to postnatal day 19) and acute treatments with the selective delta-antagonist naltrindole (1 mg/kg), on behavioural and nociceptive responses in 20-day old male rats. Behavioural testing was performed using an open field paradigm. Acute naltrindole induced significant decreases in external and total ambulation (horizontal activity) and rearing behaviour (vertical activity), as well as a significant increase in grooming frequency. In animals chronically treated with naltrindole there was an increase in total ambulation one day after the discontinuation of the treatment. In a test of nociception (tail immersion) no significant effect of chronic naltrindole treatment on baseline latencies or of acute naltrindole on latency quotients (post-treatment latency/pre-treatment latency) were found. However, chronic naltrindole administration significantly decreased the latency quotients. The results show that the delta-opioid receptor participates in the tonic regulation of motor activity during the preweanling period and might be involved in certain aspects of stress responsiveness.     

Replenishment of glutathione levels improves mucosal function in experimental acute colitis

Because reactive oxygen species (ROS) have been implicated as mediators of inflammatory bowel disease (IBD), the purpose of the present work was to determine the functional role of mucosal GSH in the trinitrobenzenesulfonic acid in 50% ethanol (TNBS+ethanol)-induced colitis in rats. Mucosal samples were taken to evaluate the temporal relationship between the extent of injury, the levels of glutathione (GSH) during acute colitis induced by TNBS+ethanol, and the effect of N-acetylcysteine (NAC) administration. In vitro assays revealed the interaction of TNBS with GSH leading to the almost instantaneous disappearance of GSH, while the reductive metabolism of TNBS by GSSG reductase generated ROS. Mucosal samples from TNBS+ethanol-treated rats indicated a direct correlation between GSH depletion and injury detected as soon as 30 minutes after TNBS+ethanol administration that persisted 24 hours post treatment. Although, short term depletion of mucosal GSH per se by diethylmaleate did not result in mucosal injury, the oral administration of NAC (40 mM) 4 hours after TNBS+ethanol treatment increased GSH stores (2-fold), decreasing the extent of mucosal injury (60-70%) examined at 24 hours post treatment. However, an equimolar dose of dithiothreitol failed to increase GSH levels and protect mucosa from TNBS+ethanol-induced injury. Interestingly, GSH levels in TNBS+ethanol-treated rats recovered by 1-2 weeks, an effect that was accounted for by an increase of gamma-glutamylcysteine synthetase (gamma-GCS) activity due to an induction of gamma-GCS-heavy subunit chain mRNA. Thus, TNBS promotes two independent mechanisms of injury, GSH depletion and ROS generation, both being required for the manifestation of mucosal injury as GSH limitation renders intestine susceptible to the TNBS-induced ROS overgeneration. Accordingly, in vivo administration of NAC attenuates the acute colitis through increased mucosal GSH levels, suggesting that GSH precursors may be of relevance in the acute relapse of IBD.