Chromosomal Distribution of Schizophrenia Susceptibility Loci

In order to find the chromosomal distribution of polymorphic loci associated with the schizophrenia risk, the present study was carried out. Meta-analysis studies with information of genetic polymorphisms and schizophrenia risk were identified and used for the present study. There were 39 loci associated with schizophrenia risk. Statistical analysis revealed that the schizophrenia susceptible loci distributed non-randomly on human chromosomes. Human chromosome segments 6p21.1-p22.3 (P?<?0.001) bear significantly higher number of susceptible loci.     

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces the only known form of secretion of active interleukin-1β and interleukin-18. Although the importance of interleukin-1β in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid-interleukin-1β and grouped the participants based on current periodontal disease classifications. We review data on 4910 European-Americans that correlate 16 polymorphisms in the interleukin-1B region with high gingival crevicular fluid-interleukin-1β levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase-1 inhibitor, VX-765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.     

Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination

Despite considerable evidence that cell activation enhances human immunodeficiency virus-type 1 (HIV-1) replication in vitro, there is very little data on the role of immune activation on in vivo HIV-1 replication. In this study, we examined the effect of influenza vaccination on HIV-1 replication in the peripheral blood of 20 study subjects, and in 14 control subjects who did not receive influenza vaccination. Blood was obtained from each subject on three occasions during the month before vaccination and again on three occasions during the following month. Over the study period, there was little change in levels of proviral DNA in peripheral blood mononuclear cells (PBMCs). However, peak PBMC viral RNA levels after influenza vaccination were significantly increased over the mean of prevaccination values. This change was not observed to the same extent in unvaccinated controls. Therefore, this is the first report showing that HIV-1 replication can increase in temporal association with influenza vaccination. Our results suggest that continued immunologic (antigenic) stimulation may result in increased virus load in vivo. To address the appropriateness of influenza vaccination in HIV-infected patients, expanded studies will be required to examine specific and generalized immune responses to vaccination, and differences in patient response based on disease stage.     

Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori eradication

AIM: To determine the efficacy of two quintupleregimens for eradication of Helicobacter pylori(H. pylori) in patients who failed previous therapies.METHODS: This prospective, open-label, randomized controlled trial was a phase Ⅱ study conducted from April 2011 to March 2012 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia who failed previous H. pylori eradication with a ten-day quadruple therapy were enrolled. A random block method was used to assign patients to one of two treatment groups. Patients in the first group were treated with 240 mg bismuth subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500 mg tinidazole(BOACT group). Patients in the second group received a regimen containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500 mg metronidazole and 200 mg ofloxacin(BOTMO group). Both regimens were given twice daily for a duration of seven days. The eradication was confirmed by a 14 C urea breath test 12 wk after completion of therapy. Patient compliance and drug side effects were evaluated at the end of the treatment period. The success rates were calculated by intention-to-treat and per-protocol analyses.RESULTS: A total of 205 patients completed the course of treatment, with three patients excluded due to drug intolerance. The mean age of patients did not differ between the BOACT and BOTMO groups(41.6 ± 12.2 years vs 39.6 ± 11.8 years), and no significant differences were found between the two groups in terms of age, sex, smoking habits or the initial eradication regimen. The intention-to-treat and perprotocol eradication rates were significantly higher in the BOTMO group(86.5%, 95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the BOACT group(75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively)(P 0.05). Univariate analyses for both groups did not show any association of sex, smoking and initial therapeutic regimen witheradiation rate(P 0.05 for all). Significantly more patients experienced side effects in the BOACT group compared to the BOTMO group(77.4% vs 36.6%, P 0.01). This difference was exemplified by increases in headache and taste disturbance(P 0.05).CONCLUSION: Quintuple therapy with a BOTMO regimen is an alternative second-line rescue therapy for Iranian patients with failed first-line eradication treatment of H. pylori.