CNS access of selected H3-antagonists: ex vivo binding study in rats

Inflammation Research -     

Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients

Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.     

HIV prevalence among female sex workers,drug users and men who have sex with men in Brazil: A Systematic Review and Meta-analysis

Background  

The Brazilian response towards AIDS epidemic is well known, but the absence of a systematic review of vulnerable populations ─ men who have sex with men (MSM), female sex workers (FSW), and drug users (DU) remains a main gap in the available literature. Our goal was to conduct a systematic review and meta-analysis of studies assessing HIV prevalence among MSM, FSW and DU, calculating a combined pooled prevalence and summarizing factors associated the pooled prevalence for each group.     

Adherence to antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome among drug users: a systematic review

AIMS: Adherence to highly active antiretroviral therapy (HAART) is a key predictor of survival for human immunodeficiency virus (HIV)-infected people. Suboptimal adherence among marginalized populations such as HIV-positive drug users could be associated with clinical failure and the emergence of viral resistance. OBJECTIVE: To conduct a systematic review of studies assessing adherence to HAART among HIV-positive drug users (DU) and identify factors associated with non-adherence to HIV treatment. DATA SOURCES: Seven electronic databases were searched for peer-reviewed papers published in English, French, Spanish or Portuguese, from 1996 to 2007. STUDY SELECTION AND DATA ABSTRACTION: Studies were excluded if they presented only qualitative data, were reviews themselves or assessed other populations without disaggregating data on DU. Findings on adherence were extracted and summarized. DATA SYNTHESIS: Forty-one studies were considered, which studied a total of 15 194 patients, the majority of whom were HIV-positive DU (n = 11 628, 76.5%). Twenty-two studies assessed adherence using patient self-reports, eight used pharmacy records, three used electronic monitoring [i.e. Medication Event Monitoring Systems (MEMS) caps], six studies used a combination of patient self-report, clinical data and MEMS-caps, and two analyzed secondary data. Overall, active substance use was associated with poor adherence, as well as depression and low social support. Higher adherence was found in patents receiving care in structured settings (e.g. directly observed therapy) and/or drug addiction treatment (especially substitution therapy). CONCLUSION: While lower than other populations-especially among users of stimulants, incarcerated DU and patients with psychiatric comorbidities-adherence to HAART among HIV-positive DU can be achieved. Better adherence was identified among those engaged in comprehensive services providing HIV and addiction treatment with psychosocial support.     

Adherence to Antiretroviral Therapy Among HIV-Infected Drug Users: A Meta-Analysis

We conducted a meta-analysis of studies assessing adherence to highly active antiretroviral therapy (HAART) and a qualitative systematic review of factors associated with better HAART outcomes among HIV+ drug users (DU). Thirty-eight studies were considered, which analyzed 14,960 patients (11,394 HIV+ DU, 76.2%). Overall adherence (pooled percent of DU classified as adherent in each study) was 0.60 (95% CI: 0.52–0.68), similar to levels identified by studies conducted with HIV+ patients who are not drug users. Time frame used to measure adherence was an independent predictor of inter-study heterogeneity. The systematic review identified better HAART outcomes among former DU, those with less severe psychiatric conditions, those receiving opioid substitution therapy and/or psychosocial support. Patients initiating HAART with lower viral load and higher CD4 counts, and those without co-infections also had better treatment outcomes. Our findings suggest that HIV+ DU tend to be inappropriately assumed to be less adherent and unlikely to achieve desirable treatment outcomes, when compared to their non-DU cohort.     

Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27

Cytogenetic, molecular and functional analysis has shown that chromosome region 6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in several solid and hematologic malignancies. We have cloned at 6q27 and characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated in tumor tissues, but its expression is significantly reduced in 30% of primary ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4 and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When tumors were induced by RNASE6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/H6cl2T cells, derived from a human/mouse monochromosomic hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4 clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40-immortalized cell line, transfected with RNASE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may be a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.