Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

Pathological and molecular analysis of Turkey coronavirus replication in captive wild Turkey embryos (broad-breasted bronze breeder)

The degree of genetic and pathologic variation exhibited by a turkey Coronavirus (TCoV) strain was investigated after nine serial passages in 25-day-old turkey embryos obtained from wild broad-breasted bronze breeders. In spite of spleen, liver, kidneys, cloacal bursa and thymus have been collected and analysed, the main histopathological changes were only documented in the intestine sections. Microscopic lesions were characterized as mild enteritis, low degree of enterocyte vacuolization and detachment of the intestinal villous after five consecutive passages and were considered absent in the last passages. Genealogic analysis based on S1 and S2 DNA sequences suggested that Brazilian isolate might be considered as originated from TCoV strains circulating in the United States, as 100% identity with TCoV-Gl strain. Although S1 S2 sequences from each passage revealed no significant point mutations, and no correlation could be speculate between S2 nucleotide changes and pathologic features in infected embryos. This is the first demonstration of wild turkey embryos as a model for TCoV isolation and propagation.

Atividade viral do vírus respiratório sincicial bovino (brsv) em bezerros leiteiros

The purpose of the present study was to evaluate the antimicrobial activity of propolis extracts diluted in different solvents against bacteria from Staphylococcus genus. The study was performed in the Immunology and Microbiology Laboratory from Universidade Federal do Vale do São Francisco. The propolis extracts were prepared using brown propolis diluted in different solvents such as chloroform, methanol, ethyl acetate and grain alcohol. In order to determine the antimicrobial potential of extracts, agar well diffusion method was used, with controls for each diluent. After that, Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) methods were used. All tests were performed in triplicate. In the agar well diffusion test, the measurements of the inhibition zone for propolis extract were as follows: grain alcohol and propolis (2.88mm), methanol and propolis (2.41mm), chloroform and propolis (2.40mm) and ethyl acetate and propolis (0.83mm). The MBC of propolis extracts in different solvents were 93.75 μg/mL for grain alcohol, 375 μg/mL for chloroform and methanol and 3,000 μg/ml for ethyl acetate. Statistically significant differences were achieved comparing the inhibition zones of propolis diluted in grain alcohol and ethyl acetate (2.88 and 0.83 mm, respectively). Considering the low cost of therapy and the activity of the propolis against caprine mastitis pathogens, other studies regarding in vivo activity and chemical characterization are necessary, in addition to evaluation of the toxicological aspects of propolis extracts.

Infecção pelo vírus da diarreia viral bovina em vacas gestantes abatidas no Estado de São Paulo-Brasil

The most important pathogens in the bovine livestock nowadays in the virus of the viral diarrhea mainly for triggered clinical manifestations related to the reproductive sphere. The infection in pregnant females, may result in abortions, embryonic resorptions, fetal mummification, birth of weak and malformation of the cattle. Moreover, their birth with persistently infected and immunotolerant virus, which the source of infection and dissemination of their disease. Nowadays, the complexity of the diagnosis and consequently its pathogenesis are tilted in the genotypic differences agent. So, this study aimed to verify the occurrence of the BVDV-1 (SINGER) and BVDV-2 (VS-253) genotypes in cows and their respective fetuses, slaughtered in an abattoir in the State of Sao Paulo. Through blood serum, using virus neutralization technique. All in all, 52,51% (115/219) of the cows which were tested reacted, but no fetus (0/219) reacted, to its virus neutralization. Through this cross-examination we observed that 42% (92/219) of cows reacted for both BVDV-1 and BVDV-2. Furthermore 4,10% (9/219) of them reacted only to the genotype BVDV-1 and 6,39% (14/219) responded only to the genotype 2 of BVDV. Therefore it was noticed that both strains are widespread in the regions studied, which justifies the use of different antigens to avoid false-negative diagnosis. Finally antibodies showed no fetus or fetal abnormalities, it is already developed and can be considered immunocompetent, independent child born to a reagent.

Intensified peginterferon α-2a dosing increases sustained virologic response rates in heavy, high viral load hepatitis c genotype 1 patients with high low-density lipoprotein

BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS, genotype 1 patients with baseline HCV RNA≥400,000 IU/mL and body weight ≥85 kg were randomized to 48 weeks of 180 μg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 μg/wk PegIFN α-2a followed by 36 weeks of 180 μg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86×10 IU/mL) versus patients with low LDL (n=262; 4.02×10 IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS: Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight. Copyright © 2013 by Lippincott Williams & Wilkins.

Bovine herpesvirus type 5 infection regulates Bax/BCL-2 ratio

Bovine herpesvirus 5 (BoHV-5) is an α-herpesvirus that causes neurological disease in young cattle and is also occasionally involved in reproductive disorders. Although there have been many studies of the apoptotic pathways induced by viruses belonging to the family Herpesviridae, there is little information about the intrinsic programmed cell death pathway in host-BoHV-5 interactions. We found that BoHV-5 is able to replicate in both mesenchymal and epithelial cell lines, provoking cytopathology that is characterized by cellular swelling and cell fusion. Viral antigens were detected in infected cells by immunofluorescence assay at 48 to 96 h post-infection (p.i.). At 48 to 72 h p.i., anti-apoptotic BCL-2 antigens were found at higher levels than Bax antigens; the latter is considered a pro-apoptotic protein. Infected cells had increased BCL-2 phenotype cells from 48 to 96 h p.i., based on flow cytometric analysis. At 48 to 96 h p.i., Bax mRNA was not expressed in any of the infected cell monolayers. In contrast, BCL-2 mRNA was found at high levels at all p.i. in both types of cells. BoHV-5 replication apparently modulates BCL-2 expression and gene transcription, enhancing production of virus progeny. © FUNPEC-RP.

Impact of Epstein-Barr virus load, virus genotype, and frequency of the 30bp deletion in the viral BNLF-1 gene in patients harboring the human immunodeficiency virus

Patients infected with the human immunodeficiency virus (HIV) are at higher risk of developing Epstein-Barr Virus (EBV)-associated lymphomas. The usefulness of monitoring EBV in peripheral blood mononuclear cells (PBMCs) of patients infected with HIV has not been established. The aim of this study was to evaluate the EBV viral load in PBMCs, the frequency of viral genotypes, and the presence of the 30-bp deletion in the BNLF-1 gene. DNA samples from 156 patients attending the HIV/AIDS Day Clinic at Botucatu School of Medicine, Sao Paulo State University were evaluated. The EBV viral load was detectable by real time PCR in 123/156 (78.8%) cases and was higher in patients not receiving antiretroviral treatment or under therapeutic failure than in patients under successful highly active antiretroviral therapy (HAART) (P=0.0076). Overall, the profile of patients with high EBV viral load included elevated HIV viremia (P=0.0005), longer time of HIV diagnosis (P=0.0026), and increased levels of T CD8 + lymphocytes (P=0.0159). The successful amplification of the EBNA-2 gene by nested-PCR was achieved in 95 of 123 (77.2%) cases, of which 75.8% were EBV-1, 9.5% EBV-2, and 14.7% were co-infected with both EBV-1 and -2. The analysis of the BNLF-1 gene was possible in 99 of 123 (80.5%) cases, of which 50.5% had the 30-bp deletion. EBV-1 was more common than EBV-2, which may reflect the fact that the cohort was predominantly Caucasian and heterosexual. J. Med. Virol. 85:2110-2118, 2013. © 2013 Wiley Periodicals, Inc.

Modelagem molecular da interação entre a proteína de fusão do vírus sincicial respiratório humano e inibidores da ação viral. -

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Validação de recursos de cargas viral do HIV-1 obtidos para insumos/kids/equipamentos de diferentes procedênias

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

Estudo da influência da infecção pelo Mycobacterium tuberculosis sobre a replicação do HIV e a imunidade celular em associação com os polimorfismos dos genes tlr2 e tlr4

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Perfil de resistência genótica do HIV-1 em pacientes com falha na terapia antirretroviral atendidos pela Rede Nacional de Genotipagem (RENAGENO) na região de Botucatu, SP-Brasil

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

Avaliação da carga viral do virus da hepatite C em diferentes compartimentos biológicos: influência na predição da recidiva virológica

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

Variabilidade da protease NS3 do vírus da hepatite C e avaliação das mutações de resistência em pacientes não tratados com inibidores de protease

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

Avaliação histopatológica, imunoistoquímica e detecção molecular do DNA viral no sistema nervoso central de bovinos inoculados experimentalmente com herpesvirus bovino 5

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo das alterações linfocitárias CD4/CD8 e carga viral em pacientes co-infectados HIV/Mycobacterium tuberculosis associadas a frequência de mutações na região Pol do HIV-1

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR