Situação imunológica dos profissionais de saúde de um laboratório de pesquisa em relação ao vírus da hepatite B

A Hepatite B continua sendo um sério problema de saúde pública, em particular aos trabalhadores da saúde, que têm risco aumentado de adquirir esta enfermidade, pelo contato com pacientes ou materiais infectados, na ocorrência de acidentes e, não raro, na falta de medidas preventivas. O presente estudo objetivou determinar a prevalência dos marcadores sorológicos da infecção pelo VHB, entre trabalhadores de um instituto de pesquisas, por meio de estudo descritivo e epidemiológico. Foram coletadas 528 amostras de sangue, de janeiro a abril de 2008, para análise dos marcadores sorológicos da hepatite B por técnicas imunoenzimáticas, detectando-se uma prevalência total de 39,7% para algum marcador do VHB, com 0,4% HBsAg⁺; 8,0% anti-HBc⁺/HBs⁺; 2,5% anti-HBc⁺ isolado e 28,8% anti- HBs⁺ isolado. Entre os entrevistados 31,6% eram vacinados contra a hepatite B, havendo entre esses 38,9% de indivíduos não respondedores à vacina e 80,8% suscetíveis, constituídos de indivíduos não vacinados e de não respondedores à vacinação. Esses resultados mostraram a necessidade de cumprir a Norma Regulamentadora 32, do Ministério do Trabalho e Emprego, que versa sobre a segurança do trabalhador em saúde.

Análise da expressão de miRNAs em carcinoma hepatocelular

O carcinoma hepatocelular corresponde à neoplasia maligna primária mais comum do fígado e ao quinto tumor sólido mais frequente no mundo. Altamente letal, permanece como um grave problema de saúde pública em virtude das dificuldades no diagnóstico precoce e na elaboração de medidas terapêuticas efetivas. Estudos recentes no ramo da biologia molecular sugerem que o perfil de miRNAs no carcinoma hepatocelular pode influir consideravelmente na identificação de fatores de riscos associados a oncogenes ou genes supressores. Objetivou-se avaliar a expressão de miRNA 135b, miRNA 181a-5p e miRNA 181a-3p em amostras de Carcinoma Hepatocelular e de Hepatite C Crônica e correlacioná-las de maneira a buscar prováveis biomarcadores relacionados ao mecanismo de carcinogenese. A investigação foi feita em seis pacientes com carcinoma hepatocelular e vinte e quatro casos de Hepatite C Crônica, procedentes do Pará, Norte do Brasil. Todas as amostras de Carcinoma Hepatocelular foram submetidas à microdissecção, para posterior extração do RNA. Para a extração do RNA total e do microRNA foi utilizado o kit AllPrep DNA/RNA FFPE Kit (Qiagen), quantificados pelo equipamento Qubit® 2.0 Fluorometer (Invitrogen) para concentração padrão final de 5ng/μL. Em seguida cDNA foi obtido, utilizando-se TaqMan® MicroRNA Reverse Transcription(AppliedBiosystems). As análises estatísticas foram realizadas nos softwares SPSS 17.0, usando o teste de Mann-Whitney, considerando como significantes valores de p<0,05. Os resultados demonstraram diferenças significativas dos níveis de expressão do miR181a-3p e do miR181a-5p no carcinoma hepatocelular (médias 3,94 e 17,9, respectivamente) em relação à hepatite C crônica (médias de 1,18 e 1,8, respectivamente) com P valor de 0,005 e 0,003. Nesse estudo, observou-se que os miRNAs 181a-3p e 181a-5p, especialmente o 181a-5p, foram significativamente mais expressos nas amostras de carcinoma hepatocelular, quando comparados ao tecido hepático não tumoral com hepatite C crônica. Portanto, os microRNAs possuem características interessantes que os favorecem como possíveis marcadores biológicos no rastreamento de tumores para diagnóstico precoce e terapias alvo selecionadas.

Acidentes de trabalho com material biológico e o seu significado para os profissionais envolvidos

Pós-graduação em Enfermagem (mestrado profissional) - FMB

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

Perfil de mutações de resistência e polimorfismos genéticos em variantes do vírus da hepatite B circulantes na região de Botucatu

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Um Modelo Espacial para a Resposta Imunológica Adaptativa da Hepatite B

This paper proposed a two-dimensional spatial model to describe the adaptive immune response for viral hepatitis B. This model considered six populations: healthy hepatocytes T, infected hepatocytes Y , hepatitis B virus V , innate immune system I, active immune system X and memory cells, X. First, a compartmental model was constructed and its equilibrium solutions and also the threshold values related to the stability of each solution were obtained. Using this model, we was able to reproduce the different trends observed for the disease, which are: individuals that eliminate the infection without forming immune response, patients with acute and chronic carriers. By including dispersion of defense cells of the immune system and virus (spatial model), we analyze two situations: homogeneous model, in which the model parameters are the same at all points of the network, and heterogeneous model, which characterizes cells more permeable and less permeable to virus invasion. For the two spatial models (homogeneous and heterogeneous) the times relatead to the viral erradication and/or virus invasion and persistence becoming smaller in relation to the compartmental model. The results also showed that for the set of values used in the simulations and if the two diffusion rates are different from zero, the model is sensitive to variations in the rate of viral spread and not dependent on the dispersion of memory cells. Finally, the heterogeneous model when compared to the homogeneous model shows that the infection can be spatially limited depending on the type of the cell involved in the infection process

Pesquisa de genomas virais em primatas não humanos do novo mundo por metagenômica

Pós-graduação em Medicina Veterinária - FMVZ

Síntese de aminochalconas e análogos arílicos como agentes antivirais, antifúngicos e inibidores de mieloperoxidase

Pós-graduação em Química - IBILCE

Systematic analysis of protein-detergent complexes applying dynamic light scattering to optimize solutions for crystallization trials

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Lack of reproductive toxicity in adult male rats exposed to interferon-alpha

Interferon-alpha (IFN- α ), a type I IFN, is a protein with antiviral, antiproliferative, and immunoregulatory activities, widely used in the treatment of several types of cancers as well as hepatitis B and C. Decrease of libido and erectile dysfunction are commonly reported by male patients during treatment of chronic hepatitis C with IFN- α . However, IFN therapy-associated underlying factors attributed to sexual dysfunction are still not well defined. Currently, there are few studies investigating the effects of IFN on male reproductive system functions. Given that, the aim of the present investigation was to examine effects of subchronic exposure to IFN- α (5 × 10(4) U/kg and 10 × 10(4) U/kg, 30 d) on serum hormones, sperm parameters, fertility, and testicular and epididymal hystopathology and morphometry in adult male Wistar rats. None of the evaluated parameters was markedly altered by IFN- α . Thus, our results suggest that exposure to IFN- α , in this experimental design, did not adversely affect sperm quality and fertile capacity of male rats.

Leprosy reactions: coinfections as a possible risk factor

OBJECTIVE: This study aimed to determine the frequency of coinfections in leprosy patients and whether there is a relationship between the presence of coinfections and the development of leprosy reactional episodes. METHOD: A cross-sectional study based on an analysis of the medical records of the patients who were treated at the Leprosy Clinics of the Ribeirao Preto Medical School, University of Sao Paulo, was conducted from 2000 to 2010. Information was recorded regarding the age, sex, clinical status, WHO classification, treatment, presence of reactions and coinfections. Focal and systemic infections were diagnosed based on the history, physical examination, and laboratory tests. Multinomial logistic regression was used to evaluate the associations between the leprosy reactions and the patients' gender, age, WHO classification and coinfections. RESULTS: Two hundred twenty-five patients were studied. Most of these patients were males (155/225 = 68.8%) of an average age of 49.31 +/- 15.92 years, and the most prevalent clinical manifestation was the multibacillary (MB) form (n = 146), followed by the paucibacillary (PB) form (n = 79). Erythema nodosum leprosum (ENL) was more prevalent (78/122 = 63.9%) than the reversal reaction (RR) (44/122 = 36.1%), especially in the MB patients (OR 5.07; CI 2.86-8.99; p<0.0001) who exhibited coinfections (OR 2.26; CI 1.56-3.27; p<0.0001). Eighty-eight (88/225 = 39.1%) patients exhibited coinfections. Oral coinfections were the most prevalent (40/88 = 45.5%), followed by urinary tract infections (17/88 = 19.3%), sinusopathy (6/88 = 6.8%), hepatitis C (6/88 = 6.8%), and hepatitis B (6/88 = 6.8%). CONCLUSIONS: Coinfections may be involved in the development and maintenance of leprosy reactions.

Evaluation of tropical water sources and mollusks in southern Brazil using microbiological, biochemical, and chemical parameters

Florianopolis, a city located in the Santa Catarina State in southern Brazil, is the national leading producer of bivalve mollusks. The quality of bivalve mollusks is closely related to the sanitary conditions of surrounding waters where they are cultivated. Presently, cultivation areas receive large amounts of effluents derived mainly from treated and non-treated domestic, rural, and urban sewage. This contributes to the contamination of mollusks with trace metals, pesticides, other organic compounds, and human pathogens such as viruses, bacteria, and protozoan. The aim of this study was to perform a thorough diagnosis of the shellfish growing areas in Florianopolis, on the coast of Santa Catarina. The contamination levels of seawater, sediments, and oysters were evaluated for their microbiological, biochemical, and chemical parameters at five sea sites in Florianopolis, namely three regular oyster cultivation areas (Sites 1, 2, and oyster supplier), a polluted site (Site 3), and a heavily polluted site (Site 4). Samples were evaluated at day zero and after 14 days. Seawater and sediment samples were collected just once, at the end of the experiment. Antioxidant defenses, which may occur in contaminated environments in response to the increased production of reactive oxygen species (ROS) by organisms, were analyzed in oysters, as well as organic compounds (in oysters and sediment samples) and microbiological contamination (in oysters and seawater samples). The results showed the presence of the following contaminants: fecal coliforms in seawater samples (four sites), human adenovirus (all sites), human noroviruses GI and GII (two sites), Hepatitis A viruses (one site), JC Polyomavirus in an oyster sample from the oyster supplier, Giardia duodenalis cysts, and Cryptosporidium sp oocysts (one site). Among organochlorine pesticides, only DDT (dichlorodiphenyltrichloroethane) and HCH (hexachlorocyclohexane) were detected in some sediment and oysters samples in very low levels; site 4 had the highest concentrations of total aliphatic hydrocarbons. PAHs, and linear alkylbenzenes (LABs) found either in oysters or in sediment samples. The major concentration of fecal sterol coprostanol was found at site 4, followed by site 3. After 14 days of allocation in the four selected sites, there was a significant difference in the enzymes analyzed at the monitored spots. The detection of different contaminants in oysters, seawater, and sediment samples in the present study shows the impact untreated or inadequately treated effluents have on coastal areas. These results highlight the need for public investment in adequate wastewater treatment and adequate treatment of oysters, ensuring safe areas for shellfish production as well as healthier bivalve mollusks for consumption.

Protease Inhibitor and Metabolic Alteration

Protease inhibitors (PIs), part of HAART (Highly Active Antiretroviral Therap) are selective, competitive inhibitors of protease, a crucial enzyme to viral maturation, infection and replication. A lipodystrophic syndrome has been reported in individuals treated with HAART, and associated to hyperglycemia, hypercholesterolemia, hypertrigliceridemia, hyperlipidemia, hypertension and hypreinsulinemia. The HAART-associated metabolic abnormalities were first associated with protease inhibitors, Ritonavir mostly, but the mechamisns that underlie these metabolic alterations are to date, not completely understood. Since Pis are candidate to be the drug of choice for other diseases treatment, such as the Hepatitis C, malaria and some types of cancer, it seems to be important to clarify the metabolic alterations associated to PIs. Wistar rats were treated twice a week with 30mg/kg Ritonavir for 4 and 8 weeks. Total cholesterol, HDL, LDL, VLDL, triglycerides and glycemic levels were measured by the end of each period of time selected. To avoid confunding effects of food intake, the animals were fasted 16 hours before. Our results showed rapid increase in serum triglycerides, total cholesterol, LDL-C and glycemic levels. No significant differences were observed for HDL-C or VLDL serum levels. Our study addresses the importance to observe the possible family history of dyslipidemia or diabetes, and control any other cardiovascular and diabetes risk factors when using protease inhibitors

Viral contamination during sequential phacoemulsification surgeries in an experimental model

Purpose: To determine the incidence of Piry virus contamination among surgical instruments used with disposable accessories for phacoemulsification during sequential surgeries. Methods: An experimental model was created with 4 pigs' eyes that were contaminated with Piry virus and 4 pigs' eyes that were not contaminated. Phacoemulsification was performed on the eyes, alternating between the contaminated and non-contaminated eyes. From one surgery to another, the operating fields, gloves, scalpel, tweezers, needles, syringes, tips and bag collector from the phacoemulsification machine were exchanged; only the hand piece and the irrigation and aspiration systems were maintained. Results: In the collector bag, three samples from the contaminated eyes (3/4) were positive, and two samples from the non-contaminated (2/4) eyes were also positive; at the tip, one sample from the contaminated eyes (1/4) and two samples of the noncontaminated eyes (2/4) yielded positive results. In the irrigation system, one sample from a non-contaminated eye (1/4) was positive, and in the aspiration system, two samples from contaminated eyes (2/4) and two samples from non-contaminated eyes (2/4) were positive. In the gloves, the samples were positive in two samples from the non-contaminated eyes (2/4) and in two samples from the contaminated eyes (2/4). In the scalpel samples, three contaminated eyes (3/4) and none of the non-contaminated eyes (0/4) were positive; finally, two samples from the anterior chambers of the non-contaminated eyes gathered after surgery were positive. Conclusions: In two non-contaminated eyes, the presence of genetic material was detected after phacoemulsification surgery, demonstrating that the transmission of the genetic material of the Piry virus occurred at some point during the surgery on these non-contaminated eyes when the hand piece and irrigation and aspiration systems were reused between surgeries.