Seroprevalence of Hepatitis B virus infection among an afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.

Amino acids of the alpha1B-adrenergic receptor involved in agonist binding: differences in docking catecholamines to receptor subtypes.

Site-directed mutagenesis and molecular dynamics analysis of the 3-D model of the alpha1B-adrenergic receptor (AR) were combined to identify the molecular determinants of the receptor involved in catecholamine binding. Our results indicate that the three conserved serines in the fifth transmembrane domain (TMD) of the alpha1B-AR play a distinct role in catecholamine binding versus receptor activation. In addition to the amino acids D125 in TMDIII and S207 in TMDV directly involved in ligand binding, our findings identify a large number of polar residues playing an important role in the activation process of the alpha1B-AR thus providing new insights into the structure/function relationship of G protein-coupled receptors.

Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis

While dementia affects 6-10% of persons 65 years or older, industrialized countries have witnessed an alarming rise in obesity. However, obesity's influence on dementia remains poorly understood. The conducted a systematic review and meta-analysis. PUBMED search (1995-2007) resulted in 10 relevant prospective cohort studies of older adults (40-80 years at baseline) with end points being dementia and predictors including adiposity measures, such as body mass index (BMI) and waist circumference (WC). There was a significant U-shaped association between BMI and dementia (P= 0.034), with dementia risk increased for obesity and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for underweight, overweight and obesity compared with normal weight in relation to incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimer's disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31) and were stronger in studies with long follow-up (>10 years) and young baseline age (

Human immunodeficiency virus type- 1 subtypes of infected patients in Espírito Santo, Brazil

Genetic variability of human immunodeficiency virus type - 1(HIV-1) is a potential threat for both diagnosis and treatment of HIV/AIDS, as well as the development of effective vaccines. Up to now, HIV subtypes circulating among HIV-positive patients in the state of Espírito Santo were not known. In the present study, blood samples from 100 therapy-naïve HIV-1 infected patients were collected and the HIV subtype was determined through the Heteroduplex Mobility Assay (HMA). Ninety-seven out of 100 studied samples were subtyped by HMA, 73 samples (75.2%) were from subtype B, 9 (9.3%) from subtype F, 3 (3.1%) from subtype C, 6 (6.2%) Benv/Fgag, and another 6 (6.2%) Fenv/Bgag, what suggests that recombinant viruses were present in the studied samples. Twenty-eight percent of the subtype B samples were represented by the Brazilian B" subtype, which were identified by RFLP with Fok I. Data presented here demonstrate that the epidemiological characteristics of the HIV epidemic in the state of Espírito Santo are similar to those from the other Southeastern states and helped to better understand the genetic polymorphism of HIV in Brazil.

Comparison of the epidemiology, profile of mutations, and clinical response to antiretrovirals among subtypes B and F of the human immunodeficiency virus type 1

The authors compared demographic aspects and profile of mutations in 80 patients with subtypes B and F of human immunodeficiency type 1 (HIV-1). Genotyping of the pol region of the reverse transcriptase was performed using the ViroSeqTM Genotyping System. A total of 61 (76.2%) patients had subtype B and 19 (23.8%) subtype F of the HIV-1. Subtype F tended to be more frequent in heterosexuals and women with a low educational level, but without statistical significance. The frequency of mutations related to nucleoside reverse transcriptase inhibitors and protease inhibitors (PI) was the same in the two subtypes, but mutations related to PI at the codons 63, 77, and 71 were more frequent in subtype B, while mutations at the codons 36 and 20 predominated in subtype F. Sixty-two of the 80 patients infected with subtypes B and F were submitted to antiretroviral therapy for an average of 18-22 months. Undetectable viral loads at the end of follow-up were similar in the two groups, representing 63.8% of subtype B and 73.3% of subtype F (p = 0.715). CD4 lymphocyte counts before and after treatment were similar in the two groups. This study, despite pointing to possible epidemiological and genetic differences among subtypes B and F of HIV-1, suggests that the use of highly active antiretroviral therapy is equally effective against these subtypes.

Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil

This study aimed to analyze human immunodeficiency virus (HIV) mutation profiles related to antiretroviral resistance following therapeutic failure, and the distribution of hiv subtypes in the Northeast Region of Brazil. A total of 576 blood samples from AIDS patients presenting therapeutic failure between 2002 and 2004 were analyzed. The genotyping kit viroSeq® was used to perform viral amplification in order to identify mutations related to hiv pol gene resistance. An index of 91.1% of the patients presented mutations for nucleoside reverse transcriptase inhibitors (nrti), 58.7% for non-nucleoside reverse transcriptase inhibitors (nnrti), and 94.8% for protease inhibitors (pi). The most prevalent mutations were 184V and 215E for nrti, 103N and 190A for nnrti. Most mutations associated with PIs were secondary, but significant frequencies were observed in codons 90 (25.2%), 82 (21.1%), and 30 (16.2%). The resistance index to one class of antiretrovirals was 14%, to two classes of antiretrovirals 61%, and to three classes 18.9%. Subtype B was the most prevalent (82.4%) followed by subtype F (11.8%). The prevalence of mutations related to nrti and nnrti was the same in the two subtypes, but codon analysis related to PI showed a higher frequency of mutations in codon 63 in subtype B and in codon 36 in subtype F. The present study showed that there was a high frequency of primary mutations, which offered resistance to nrti and nnrti. Monitoring patients with treatment failure is an important tool for aiding physicians in rescue therapy.

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010.

Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. METHODS: Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. RESULTS: From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. CONCLUSIONS: The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.

Blastocystis subtypes in irritable bowel syndrome and inflammatory bowel disease in Ankara, Turkey

Blastocystis infection has been reported to be associated with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and chronic diarrhoea. The availability of data on the subtypes of Blastocystis found in these patient groups would be of interest in understanding the significance of Blastocystis infection in chronic illness. In this study, we identify Blastocystis subtypes found in patients presenting with IBS, IBD, chronic diarrhoea and asymptomatic patients in Ankara, Turkey. Blastocystis was detected in 11 symptomatic patients by microscopy and 19 by stool culture. Stool culture was more sensitive than microscopy in identifying Blastocystis. Using standard nomenclature adopted in 2007, Blastocystis sp. subtype 3 was the most common in all groups, followed by Blastocystis sp. subtype 2. Identical subtypes of Blastocystis are found in patients with IBS, IBD and chronic diarrhoea. These particular subtypes show low host specificity and are carried by humans and some farm animals. The subtypes of Blastocystis that are commonly found in rodents and certain wild birds were not found in these patients. We suggest a model in which the severity of enteric protozoan infection may be mediated by host factors.

Seroprevalence of HBV, HCV and HIV co-infection in selected individuals from state of São Paulo, Brazil

Few studies are available on hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection in populations living in small and medium-sized Brazilian cities. We evaluated the seroprevalence of these viruses in selected individuals from a clinic of infectology, who were referred to the University Regional Hospital of the West Region of state of São Paulo, Brazil. Among a total of 7,021 individuals seen in the clinic following receipt of preliminary ELISA results or having the suggested clinical signs of viral hepatitis or HIV, 1,228 were systematically screened. Isolated or associated HBsAg, HCV and HIV antibodies were found in 44.9% of the subjects. Anti-HIV antibodies were found in 24.7% of the patients, 20.3% of whom had an HIV monoinfection and 4.4% of whom were co-infected with hepatitis viruses (HCV: 4%; HBV: 0.4%). Anti-HCV antibodies were found in 14% of the patients and 5.9% had anti-HBsAg antibodies. HCV infection affected males more than females (p < 0.05) and individuals > 50-years old had an increased prevalence of anti-HCV compared to HIV (p = 0.0001) or HBV (p = 0.0063). HCV-RNA was detected in 73.5% of the samples with a predominance of genotype 1 (72.5%). A significant percentage (44.9%) of the selected individuals was positive for antibodies against HBV, HCV and/or HIV; these patients would otherwise have remained undiagnosed.

HBV markers in haemodialysis Brazilian patients: a prospective 12-month follow-up

The aim of this study was to determine the prevalence and the incidence of hepatitis B virus (HBV) among haemodialysis (HD) subjects and to evaluate whether testing for serological markers at the time of admission is suitable for HBV screening in this population. One hundred twenty-three patients belonging to two HD centres from São Paulo, Brazil, were tested prospectively. HBV DNA was detected by polymerase chain reaction (PCR) in each of the prospective subjects (n = 123) during one year. Additionally, all samples (n = 1,476) were analysed for HBV serological markers. The prevalence of hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and HBV DNA were 34.1%, 15.4% and 8.1%, respectively, while the incidence was null. Fluctuation in HBV serology was observed in one patient. Only 37.8% (17/45) of cases responded to the HBV vaccine. Our results suggest that employing more than one HBV marker and repeated follow-up evaluations may improve HBV screening in HD units.

Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients

In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80%) of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14) after treatment (AT) with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored.

The alpha 1a and alpha 1b-adrenergic receptor subtypes: molecular mechanisms of receptor activation and of drug action.

In this chapter we summarize some aspects of the structure-functional relationship of the alpha 1a and alpha 1b-adrenergic receptor subtypes related to the receptor activation process as well as the effect of different alpha-blockers on the constitutive activity of the receptor. Molecular modeling of the alpha 1a and alpha 1b-adrenergic receptor subtypes and computational simulation of receptor dynamics were useful to interpret the experimental findings derived from site directed mutagenesis studies.

Co-infections associated with human immunodeficiency virus type 1 in pregnant women from southern Brazil: high rate of intraepithelial cervical lesions

Human immunodeficiency virus type 1 (HIV-positive) pregnant women require specific prophylactic and therapeutic approaches. The efficacy of established approaches is further challenged by co-infection with other sexually transmitted diseases (STDs). The objective of this study was to determine the prevalence of co-infections in pregnant women infected with different HIV-1 subtypes and to relate these findings, together with additional demographic and clinical parameters, to maternal and infant outcomes. Blood samples from pregnant women were collected and tested for syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). Human papillomavirus (HPV) diagnosis was evaluated by the presence of alterations in the cervical epithelium detected through a cytopathological exam. Medical charts provided patient data for the mothers and children. Statistical analyses were conducted with STATA 9.0. We found a prevalence of 10.8% for HCV, 2.3% for chronic HBV, 3.1% for syphilis and 40.8% for HPV. Of those co-infected with HPV, 52.9% presented high-grade intraepithelial lesions or in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores were similar between co-infected and non-co-infected women. The presence of other STDs did not impact maternal and concept outcomes. More than half of the patients presenting cervical cytology abnormalities suggestive of HPV had high-grade squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate of these lesions.

Antiviral therapy against chronic hepatitis B in Brazil: high rates of lamivudine resistance mutations and correlation with HBV genotypes

The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).