Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

Background: The quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. The complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. The viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. In addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C. © 2013 Jardim et al.; licensee BioMed Central Ltd.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

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

Predictive formulas for food base excess and urine pH estimations of cats

Food base excess (BE, mEq/kg) can be calculated from the diet macroelements, together with either the sulfur amino acids methionine and cysteine (BEaa) or total sulfur (BEs) concentrations. The present study compared the use of sulfur or methionine and cysteine for calculating the food BE (experiment 1) and investigated the influence of food BE on blood gas analysis and the urine pH of cats, and proposes a prediction equation to estimate the urine pH of cats fed kibble diets based on the calculated food BE (experiments 2 and 3). In experiment 1, nine healthy, adult cats were used in a change-over design and fed with nine commercial dry cat foods. The cats were housed in metabolism cages over seven days for adaptation and three days for total urine collection. All of the urine produced over 24h was pooled by cat and diet. The cats' acid-base status was assessed through blood gas analysis after 10 days of diet consumption. A mean difference of -115mEq/kg between BEs and BEaa was observed, which could be explained by a greater concentration of sulfur in the whole diet than in methionine and cysteine. Urine pH presented a stronger correlation with food BEs (R2=0.95; P<0.001) than with food BEaa (R2=0.86; P<0.001). Experiment 2 included 30 kibble diets, and each diet was tested in six cats. The food BEs varied between -180 and +307mEq/kg, and the urine pH of the cats varied between 5.60 and 7.74. A significant correlation was found between the measured urine pH and the food BEs (urinary pH=6.269+[0.0036×BEs]+[0.000003×BEs2]; R2=0.91; P<0.001). In experiment 3, eight kibble diets were tested (food BEs between -187mEq/kg and +381mEq/kg) to validate the equation proposed in experiment 2 and to compare the obtained results with previously published formulae. The results of the proposed formula presented a high concordance correlation coefficient (0.942) and high accuracy (0.979) with the measured values, and the estimates of urine pH did not differ from the values obtained in cats (P>0.05). The cats' venous blood pH, bicarbonate, and blood BE were correlated with food BEs (P<0.001); the consumption of diets with low food BEs induced a reduction in these parameters. In conclusion, food macroelement composition has a strong influence on cats' acid-base equilibrium and food BEs calculation is a useful tool to formulate and balance kibble diets for felines. © 2013 Elsevier B.V.

Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats

Background: A scale validated in one language is not automatically valid in another language or culture. The purpose of this study was to validate the English version of the UNESP-Botucatu multidimensional composite pain scale (MCPS) to assess postoperative pain in cats. The English version was developed using translation, back-translation, and review by individuals with expertise in feline pain management. In sequence, validity and reliability tests were performed.Results: Of the three domains identified by factor analysis, the internal consistency was excellent for 'pain expression' and 'psychomotor change' (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in pain scores at clinically distinct time points (e.g., post-surgery, post-analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and moderate to very good agreement between blinded observers and 'gold standard' evaluations, supported criterion validity. The cut-off point for rescue analgesia was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity.Conclusions: The English version of the UNESP-Botucatu-MCPS is a valid, reliable and responsive instrument for assessing acute pain in cats undergoing ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The cut-off point for rescue analgesia provides an additional tool for guiding analgesic therapy. © 2013 Brondani et al.; licensee BioMed Central Ltd.

Representações sociais sobre a Aids e a Terapia Anti-Retroviral: influências no tratamento de pessoas vivendo com HIV/Aids

Com o advento da Terapia Anti -Retroviral, a Aids assumiu características de doença crônica, em especial nos países onde o acesso aos medicamentos é efetivamente garantido. O Brasil é tomado como modelo por possuir um programa que tem dado boas respostas à epidemia. Em novembro de 1996, foi promulgada, pelo Sistema Único de Saúde (SUS), a lei que dispõe sobre a obrigatoriedade do acesso gratuito a todos os que necessitarem de medicamentos anti -retrovirais. Os resultados obtidos com o tratamento – a redução progressiva da carga viral e a manutenção e/ou restauração do funcionamento do sistema imunológico – têm sido associados a benefícios marcantes na saúde física das pessoas soropositivas e permitido que elas retomem e concretizem seus projetos de vida. Porém, o acesso universal aos medicamentos que possibilita o tratamento para portadores do HIV gratuitamente ainda enfrenta problemas de adesão. Em uma compreensão mais restrita, adesão pode ser definida como o comportamento de uma pessoa – tomar remédio, seguir uma dieta ou fazer mudanças no estilo de vida – que corresponde às recomendações da equipe de saúde. Nesse contexto, esse estudo se propõe a analisar as representações sociais de sujeitos soropositivos sobre o tratamento anti-retroviral e suas implicações no processo de adesão a este tratamento, caracterizando as imagens e os sentidos que estes sujeitos soropositivos que aderiram ou não aderiram à terapia anti -retroviral possuem sobre este tipo de tratamento e as implicações na sua vida, destacando as objetivações e as ancoragens que compõem suas representações sociais. A metodologia foi pautada nas formulações teóricas sobre pesquisa qualitativa, priorizando -se a entrevista no enfoque do Método de Explicitação do Discurso Subjacente (MEDS), realizadas na Unidade de Referência em Doenças Infecciosas e Parasitárias Especiais (UREDIPE), vinculada à Secretaria de Estado de Saúde do estado do Pará (SESPA) e no Hospital Universitário João de Barros Barreto (HUJBB), mais especificamente na Clinica de Doenças Infecciosas e Parasitárias (DIP).

Evaluation of the therapeutic response of hepatitis C in coinfected patients (HIV/HCV): a study of cases from a hospital for chronic liver diseases in the Eastern Brazilian Amazon

INTRODUCTION: The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). METHODS: A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Fundação Santa Casa de Misericórdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). RESULTS: The mean age of the patients was 40±9.5 years, of which 89% (n=17) were male, and the HCV genotypes were genotype 1 (55%, n=11/20), genotype 2 (10%, n=2/20) and genotype 3 (35%, n=7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. CONCLUSIONS: The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.

Efeito da dieta da suplementação de ômega-3 sobre marcadores metabólicos e inflamatórios em mulheres na pós-menopausa com síndrome metabólica

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Avaliação da influência da orientação nutricional e do tratamento medicamentoso na recorrência da litíase urinária

Pós-graduação em Bases Gerais da Cirurgia - FMB

The Incidence of Dysphagia in Patients Receiving Cerebral Reperfusion Therapy Poststroke

Background: The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Methods: Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann-Whitney test and considered significant if P is less than .05. Results: The moderate and severe degrees of dysphagia were more frequent (P = .013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P = .045). Conclusions: We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. (C) 2014 by National Stroke Association

Periodontopathogens levels and clinical response to periodontal therapy in individuals with the interleukin-4 haplotype associated with susceptibility to chronic periodontitis

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

Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil

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

Arthropod-borne pathogens circulating in free-roaming domestic cats in a zoo environment in Brazil

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

Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a proportional meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Rutin ameliorates glycemic index, lipid profile and enzymatic activities in serum, heart and liver tissues of rats fed with a combination of hypercaloric diet and chronic ethanol consumption

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)