Absence of the tag polymorphism for the risk haplotype HLA-DR2 for multiple sclerosis in Wixárika subjects from Mexico.

The HLA-DRB1*15:01 allele has a demonstrated risk for the development of multiple sclerosis (MS) in most populations around the world. The single nucleotide polymorphism (SNP) rs3129934 is found in linkage disequilibrium with the risk haplotype formed by the HLA-DRB1*15:01 and HLA-DQB1*06:02 alleles, and it is considered a reliable marker of the presence of this haplotype. Native Americans have a null or low prevalence of MS. In this study, we sought to identify the frequency of rs3129934 in the Wixárika ethnic group as well as in Mestizo (mixed race) patients with MS and in controls from western Mexico. Through real-time polymerase chain reaction (PCR) using TaqMan probes, we analyzed the allele and genotype frequencies of rs3129934 in Mestizo individuals with and without MS and in 73 Wixárika subjects from the state of Jalisco, Mexico. The Wixárika subjects were homozygote for the C allele of rs3129934. The allele and genotype frequency in Mestizos with MS was similar to that of other MS populations with Caucasian ancestry. The absence of the T risk allele rs3129934 (associated with the haplotype HLA-DRB1*15:01, HLA-DQ1*06:02) in this sample of Wixárika subjects is consistent with the unreported MS in this Amerindian group, related to absence of such paramount genetic risk factor.

Association of SOD1 gene variants (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) with plasma protein levels in vitiligo patients and their analysis in silico.

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.

Nutritional Status in Patients with Probable Alzheimer's Disease: Effect of Rivastigmine.

IMPORTANCE: Altough disease-modifying factors such as malnutrition and diet have been associated with Alzheimer's disease (AD), little is known about the effects of pharmacological therapies on the nutritional status of AD patients. OBJECTIVE: To evaluate the nutritional status, prealbumin, and albumin serum levels and several anthropometric measurements in patients with probable moderate-stage AD, with and without rivastigmine drug treatment. STUDY DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: 34 patients were included, 17 with rivastigmine treatment and 17 without pharmacological treatment, over 60 years of both sexes. MEASUREMENTS: The nutritional status was evaluated using the Mini Nutritional Assessment (MNA). Albumin and prealbumin (transthyretin) levels and anthropometric evaluation were assessed using standard methods. RESULTS: A polarity of malnutrition was detected in the untreated group. According to the MNA survey, the risk of malnutrition is higher without rivastigmine treatment (p = 0.0001). There are a less loss of appetite, less psychological stress, greater mobility and independence in those patients receiving rivastigmine (p = 0.003, 0.008, 0.016 and 0.018, respectively). The body mass index does not show a statistical difference, however, categorizing it for older adults, this index was improved in those receiving rivastigmine (p = 0.016). The serum levels of albumin and prealbumin showed no significant statistical difference between the groups. CONCLUSION: Rivastigmine treatment shows a protective effect on malnutrition in patients with moderate-stage AD.

Effect of melatonin administration on the PER1 and BMAL1 clock genes in patients with Parkinson's disease.

Sleep disorders are a widespread condition in patients with Parkinson's disease (PD), which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. The aim of this study was to evaluate the effect of melatonin (MEL) on the PER1 and BMAL1 clock genes in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial pilot study was conducted in 26 patients with stage 1-3 PD according to the Hoehn & Yahr scale, who received either 25 mg of MEL or a placebo at noon and 30 min before bedtime for three months. The relative expression of the PER1 and BMAL1 genes was measured, as well as the presence of daytime, nocturnal, and global sleepiness, and the progression of PD. The levels of the PER1 and BMAL1 genes at baseline were 0.9 (0.1-3) vs. 0.56 (0.1-2.5), respectively; while after the intervention with MEL or placebo the BMAL1 levels increased to 2.5 (0-3.70) vs. 2.2 (0.10-3.30), respectively (d = 0.387). Fifty percent (50 %) of patients had daytime sleepiness and sixty-five percent (65 %) had abnormal nighttime sleepiness, yet neither group showed changes after the intervention. Patients with PD exhibited an alteration in the levels of the clock genes: MEL increased the levels of BMAL1, but the PER1 levels remained unchanged.

[Effectiveness of the modify tomographic severity index in patients with severe acute pancreatitis.]. / Eficacia del índice de gravedad tomográficomodificado en enfermos con pancreatitisaguda grave.

INTRODUCTION: Acute pancreatitis (AP) is a very important cause of morbidity and mortality in Mexico.In 2001 AP was the 17th cause of death. Since 1994,the computed tomography (CT) scan was accepted for the screening of the severity (a) according to the Computed Tomography Severity Index (CTSI). In 2004 Mortele et al., developed a new tomography classification, Modified Computed Tomography Severity Index (MCTSI) including pancreatic and extra pancreatic disease, obtaining a very good correlation with those with organ failure. This study proposes compare the tomography classifications as indicators of severity. METHODS: Cross-sectional study. Were included 30 patients with acute pancreatitis; APACHE II >= 8, non improvement with medical treatment and with initial mild pancreatitis,with addition of signs of complication in the first 72 hours of evolution, under CT scan, CTSIM and CTSI were compared. Statistical analysis using X2 test was calculated, kappa concordance coefficient(k) for the severity classifications. RESULTS: AP prevalence was 51.07%.Of the 30 patients including,19 man with mean age of 39.0 years (18-58 years),and 11 woman, with mean age of 50.9 years (22-82 years). The main causes were biliary pancreatitis in 16 cases (53.3%), and the second was alcohol,8 cases (26.7%). The kappa concordance coefficient for both tomography scans was 0.48 (p <= 0.003). For the CTSIM and CTSI sensitivity was 61% vs. 38%,specificity 66% vs. 100% and positive predictive value of 81% vs. 100%, respectively. CONCLUSIONS: The CTSIM is more useful for the screening in patients with severe acute pancreatitis than CTSI.

Anabolic androgenic steroids induce micronuclei in buccal mucosa cells of bodybuilders.

OBJECTIVE: To evaluate genotoxicity of anabolic androgenic steroids (AAS) in male bodybuilders by a micronucleus assay in buccal mucosa cells. METHODS: 11 male bodybuilders volunteered to participate in this study and two groups were formed: group 1 (n = 6), without AAS consumption and group 2 (n = 5), with AAS consumption. A sample of buccal epithelium was taken from each participant once a week for 6 weeks. Samples were fixed, stained and analysed by a light microscope, and 2000 cells were counted from each slide. Results are expressed as micronucleated cells (MNC) per 1000 cells and were analysed by the Mann-Whitney U test and Wilcoxon's test. RESULTS: A marked increased in MNC was seen in bodybuilders with AAS consumption compared with those without AAS consumption (mean (SD) 4.1 (2.4) MNC/1000 cells vs 0.4 (0.4) MNC/1000 cells, respectively; p<0.004). Intragroup comparisons showed no differences in the MNC frequencies during the sampling time in group 1, whereas the MNC frequency in group 2 varied significantly, reaching the highest MNC frequencies in the third and fourth week of sampling (5.9 (2.4) MNC/1000 cells; 5.8 (1.8) MNC/1000 cells, respectively); frequency in the first sampled week was 1.1 (0.1) MNC/1000 cells. Significant differences in all sampled weeks were found between the two groups. CONCLUSION: AAS consumption increased the frequency of MNC from buccal mucosa in bodybuilders.

Neuronal death and tumor necrosis factor-alpha response to glutamate-induced excitotoxicity in the cerebral cortex of neonatal rats.

Neuronal death and lactate dehydrogenase (LDH) activity were evaluated in the cerebral cortices of neonatal rats after exposure to monosodium L-glutamate (MSG) to induce neuroexcitotoxicity. A time-response profile for tumor necrosis factor-alpha (TNF-alpha) expression was drawn, with measurements taken every 6 h after the first dose of MSG during the first 8 postnatal days, and at days 10 and 14 after birth. An increase in neuronal loss accompanied by high LDH activity and high TNF-alpha levels was observed at 8 and 10 days. These results indicate that neuronal loss may occur via an apoptosis-like mechanism directed selectively against neurons that express glutamate receptors, mainly the N-methyl-D-aspartate, which it may be strengthen by high TNF-alpha levels through a feedback mechanism to induce cell death via apoptosis.

[Effect of potassium iodide on the immune response in the sporotrichosis.]. / Efecto del yoduro de potasio sobre la respuesta inmune en la esporotricosis.

Potassium iodide (KI), the specific treatment for sporotrichosis, apparently does not have a direct action on Sporothrix schenckii. The spontaneous healing and the variability of the clinical presentation in the disease have strengthened the idea that the KI rather interacts with the immune response of the host. The phagocytic process is inefficient in individuals with sporotrichosis in whom the microbicidal mechanism of halogenation fails to control the disease. There is evidence that blocking of free radicals decreases in the presence of KI. Humoral and cellular immunity are present in sporotrichosis but its participation is uncertain; it is yet to be determined if in this mycosis the KI influences other processes or factors of immune response.

Use of topical ketanserin for the treatment of ulcers in leprosy patients.

A comparative study was carried out in which 66 leprosy patients with ulcers were randomly divided in two groups of 33 patients each: Group A (experimental group) was treated with ketanserin gel (2%) and group B with clioquinol cream and/or Lassar paste during a three month period. At the end of the study, when ulcer sizes in the two groups were compared, the group treated with topical ketanserin showed superior results (p < 0.001 using Kolmogorov-Smirnov's test). We conclude that the drug is useful as coadjuavant treatment for healing ulcers in these patients.

Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide.

Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.

HIF-1α expression in the hippocampus and peripheral macrophages after glutamate-induced excitotoxicity.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a master transcription factor that regulates the response to hypoxia and ischemia and induces the expression of various genes, including vascular endothelial growth factor (VEGF) and erythropoietin (EPO). This study shows the systemic response of increased HIF-1α, EPO, and VEGF mRNA and protein. In addition, VEGF expression was increased in neurons and over-expressed in glial cells in a model of neuroexcitotoxicity in the hippocampus, in which rats were neonatally exposed to high glutamate concentrations. Simultaneous increases in HIF-1α, EPO and VEGF mRNA in peritoneal macrophages were also observed. Our study is consistent with the hypothesis that these genes exert a protective effect in response to neurotoxicity.

Expression of HIF-1 alpha, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia.

OBJECTIVES: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. DESIGN AND METHODS: The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. RESULTS: An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. CONCLUSIONS: HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.

Drug-resistance mutations in antiretroviral-naïve patients with established HIV-1 infection in Mexico.

OBJECTIVES: To describe the prevalence of baseline drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naïve patients from Mexico with established HIV-1 infection. METHODS: Resistance testing was performed on plasma samples from antiretroviral-naïve patients. Data on mutations associated with antiretroviral drug resistance were obtained using Stanford software (http://hivdb.stanford.edu). RESULTS: Ninety-six treatment-naïve individuals were enrolled in the study during 2002-2003. Of these, 83 patients (86%) had at least one resistance mutation and 15 (16%) had drug resistance. At baseline, the mean plasma viral load was 299 834 HIV-1 RNA copies/mL, and at follow-up it was 37 620 copies/mL (P<0.0001). Primary mutations in the reverse transcriptase region were observed in 15% of patients. For nucleoside inhibitors, mutations T215Y/C and F77L (3%) and D67N/S, T69N and M184V (2%), were detected. For nonnucleoside inhibitors, mutations K103N/R (6%), Y181C (3%) and G190A (2%) were detected. Overall, 6% of patients showed resistance to delavirdine and nevirapine, 4% to efavirenz, and 2% to lamivudine and nelfinavir. Twelve patients showed no response to treatment and three of these patients had antiretroviral drug resistance. CONCLUSIONS: The prevalence of baseline drug-resistance mutations found in this study was similar to that found in previous reports for newly HIV-infected individuals, although access to and management of antiretrovirals in Mexico are different.

[Effects of health legislation against HIV in blood donation in Guadalajara, Mexico]. / Efecto de la legislación sanitaria contra el VIH en la donación de sangre en Guadalajara, México.

In México, since may 1986, the mandatory detection of antibodies against HIV in blood and derivates for the use by humans was legislated, one year later the prohibition of blood trade took effect. The impact of the Sanitary Normativity in the seroprevalence of anti HIV antibodies between blood donors one year before and one year after it took result was compared. A sample was taken from 4743 serums of donors of 6 blood banks in Guadalajara between june 1986 and june 1988; 4020 in the first year and 723 the next. In all the samples the presence of anti HIV antibodies was determined by the ELISA assay and the positive ones were confirmed by indirect immunofluorescence and by Western blot. During the first year, the seroprevalence fluctuated between 2.02 and 30.15 percent depending on different factors, differing from the second year where the seroprevalence was 0.14 percent. It is concluded that the mandatory detection of antibodies against HIV and the prohibition of blood trade, have been definitive factors to decrease the incidence of HIV in blood donors.

Use of topical ketanserin for the treatment of ulcers in leprosy patients.

A comparative study was carried out in which 66 leprosy patients with ulcers were randomly divided in two groups of 33 patients each: Group A (experimental group) was treated with ketanserin gel (2%) and group B with clioquinol cream and/or Lassar paste during a three month period. At the end of the study, when ulcer sizes in the two groups were compared, the group treated with topical ketanserin showed superior results (p < 0.001 using Kolmogorov-Smirnov's test). We conclude that the drug is useful as coadjuavant treatment for healing ulcers in these patients.