Caffeine inhibits hepatitis C virus replication in vitro

Abstract Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-50 C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH- 1. Caffeine efficiently inhibited HCV replication in a dosedependent manner at non-cytotoxic concentrations and demonstrated an IC50 value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.

Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro

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

Estratégias tolerogênicas antígeno-específicas visando profilaxia e terapia na artrite autoimune experimental

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

Prevalence of the hepatitis C virus among university employees in São Paulo, southeastern Brazil: predictive factors and geoprocessing spatial analysis

Background There are limited studies on the prevalence and risk factors associated with hepatitis C virus (HCV) infection. Objective Identify the prevalence and risk factors for HCV infection in university employees of the state of São Paulo, Brazil. Methods Digital serological tests for anti-HCV have been performed in 3153 volunteers. For the application of digital testing was necessary to withdraw a drop of blood through a needlestick. The positive cases were performed for genotyping and RNA. Chi-square and Fisher’s exact test were used, with P-value <0.05 indicating statistical significance. Univariate and multivariate logistic regression were also used. Results Prevalence of anti-HCV was 0.7%. The risk factors associated with HCV infection were: age >40 years, blood transfusion, injectable drugs, inhalable drugs (InDU), injectable Gluconergam®, glass syringes, tattoos, hemodialysis and sexual promiscuity. Age (P=0.01, OR 5.6, CI 1.4 to 22.8), InDU (P<0.0001, OR=96.8, CI 24.1 to 388.2), Gluconergam® (P=0.0009, OR=44.4, CI 4.7 to 412.7) and hemodialysis (P=0.0004, OR=90.1, CI 7.5 – 407.1) were independent predictors. Spatial analysis of the prevalence with socioeconomic indices, Gross Domestic Product and Human Development Index by the geoprocessing technique showed no positive correlation. Conclusions The prevalence of HCV infection was 0.7%. The independent risk factors for HCV infection were age, InDU, Gluconergan® and hemodialysis. There was no spatial correlation of HCV prevalence with local economic factors.

Produção da nucleoproteína recombinante do vírus da influenza aviária para aplicação no imunodiagnóstico

Pós-graduação em Microbiologia Agropecuária - FCAV

Desenvolvimento e aplicação do Elisa indireto com a nucleoproteína recombinante (NPR) do vírus da doença de Newcastle

Pós-graduação em Medicina Veterinária - FCAV

Epidemiological profile of hepatitis C virus infection in patients from west region of Minas Gerais State, Brazil

Hepatitis C virus (HCV) is a serious public health problem and is the leading cause of liver transplantation due to cirrhosis and hepatocellular carcinoma. In Brazil, it is estimated that there are approximately 2 to 3 million HCV chronic carriers. Few data regarding HCV infection are available in West region of Minas Gerais State. Due to the absence of an effective vaccine against this important human pathogen and the high costs of antiviral treatment, it is important to conduct epidemiological studies with the purpose of carry out the planning and implementation of measures to prevent hepatitis C in different populations. Therefore, the aim of this study is to describe the epidemiological aspects of HCV patients from West region of Minas Gerais State, Brazil. Sociodemographic data and risk factors for HCV infection were determined from 74 HCV patients from Uberlandia city (Minas Gerais State). Reactive anti-HCV sera samples were submitted to HCV RNA and genotype detection. Most of individuals were male (63.5%) with mean age of 51 years and presenting low socioeconomic status. HCV genotype was determined among 40 samples and the frequencies were: genotype 2 (45%), 1 (37.5%) and 3 (17.5%). Hepatitis C virus (HCV) infection was common among male and low socioeconomic status individuals.

Amniotic membrane as a biological dressing for 5-fluoruracil-induced oral mucositis in rats

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

Expression of cellular components in granulomatous inflammatory response in piaractus mesopotamicus model

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

Comparative evaluation of several methods for Canine Visceral Leishmaniasis diagnosis

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

Effects of Yersinia enterocolitica O:3 derivatives on B lymphocyte activation in vivo

The potential sequelae of intestinal infection with Yersinia enterocolitica include reactive arthritis, erythema nodosum, Reiter's syndrome and other autoimmune diseases. The role of the immune response in the pathogenesis of these diseases has not been fully defined, but autoimmune manifestations may be a consequence of the increase in autoantibodies as a result of polyclonal B-cell activation induced by Yersinia. We investigated the effects of Y enterocolitica 0:3 derivatives on B lymphocyte activation in vivo. Groups of five specific pathogen free (SPF) Swiss mice were inoculated with bacterial cell extract, Yersinia outermembrane proteins (Yops) or lipopolysaccharide (LPS) obtained from Y enterocolitica 0:3 and their immunoglobulin-secreting spleen cells were detected by isotype-specific protein A plaque assay. The presence of specific anti-Yersinia antibodies and autoantibodies was determined in mouse sera by ELISA. In all experiments a marked increase in the number of secretory cells of different isotypes was observed as early as the third day after inoculation. IgG and IgM anti-Yersinia antibodies were detected in the sera of all inoculated mice, and autoantibodies against myosin in the sera of those inoculated with bacterial cell extract. The sera from animals stimulated with LPS reacted with myelin, actin and laminin, while the sera from mice inoculated with Yops reacted with myelin, thyroglobulin and cardiolipin. These results suggest that SPF Swiss mice inoculated with any one of the Y enterocolitica derivatives tested exhibited polyclonal activation of B lymphocytes as a result of stimulation by various bacterial components and not only LPS stimulation.

The shadows of a ghost: a survey of canine leishmaniasis in Presidente Prudente and its spatial dispersion in the western region of São Paulo state, an emerging focus of visceral leishmaniasis in Brazil

Visceral leishmaniasis is an emerging zoonosis and its geographic distribution is restricted to tropical and temperate regions. Most of the individuals infected in Latin America are in Brazil. Despite the control measures that have been adopted, the disease is spreading throughout new regions of the country. Domestic dogs are involved in the transmission cycle and are considered to be the main epidemiologic reservoir of Leishmania infantum (syn. L. chagasi). Our aim was to determine the prevalence of canine leishmaniasis (CL) and Ehrlichiosis infection in Presidente Prudente as well as the spatial dispersion of the disease in the western region of São Paulo state. Dogs underwent clinical examination and symptoms related to CL were recorded. Anti- Leishmania antibodies were detected using ELISA, rK39-immunocromatographic tests (DPP), and an indirect fluorescent antibody test (IFAT). Anti-E. canis antibodies were detected by IFAT. A follow-up was conducted in dogs that were positive in the ELISA at the baseline study. Data on the spatial distribution of L. longipalpis and CL in São Paulo state were obtained from Brazilian public health agencies. Serum samples from 4547 dogs were analyzed. The seroprevalence of CL was 11.2 % by ELISA and 4.5 % by IFAT. In the follow-up, seroprevalence was 32.9 % by ELISA, 15.3 % by IFAT, 11.8 % by DPP test, and 66.5 % for E. canis. There was a significant positive association between Leishmania and E. canis infection (P < 0.0001). In the follow-up, clinical examinations revealed symptoms compatible with CL in 33.5 % of the dogs. L. longipalpis was found in 24 and CL in 15 counties of the Presidente Prudente mesoregion. The dispersion route followed the west frontier of São Paulo state toward Paraná state. Low CL and high ehrlichiosis prevalence rates were found in Presidente Prudente city. This emerging focus of CL is moving through the western region of São Paulo state toward the border of Paraná state. Integrated actions to fight the vector, parasites, infected dogs, and humans are needed to monitor the disease and implement strategies for epidemiologic control.

Epidemiological profile of hepatitis C virus infection in patients from west region of Minas Gerais State, Brazill

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Construção de um indicador qualitativo (status de saúde) para avaliação da qualidade de saúde animal de propriedades rurais

Aiming at developing a tool for assessing the magnitude of farm animal health, an indicator named herd “animal health status” was built. To illustrate the construction of the indicator, serum samples were taken from 923 goats on 17 goat farms in the state of Sao Paulo, Brazil, where three diseases were evaluated along with their impact percentages: caprine arthritis encephalitis, toxoplasmosis and neosporose – all of an infectious and transmissible nature and the cause of considerable economic losses. The mathematical rationale underlying the building of the “animal health status” indicator ranks properties on a 0 - 100% scale in terms of disease positivity in the herd, with the lowest indicator value indicating the highest cumulative disease frequency (0% = all animals tested positive for the three diseases, 100% = all animals tested negative for all diseases). Anti-T. gondii, anti-N. caninum and anti-CAEV antibodies were tested using indirect immunofluorescence reaction (IIFR ≥ 16), Neospora agglutination test (NAT ≥ 25) and agarose gel immunodiffusion (AGID positive or negative), respectively. The animal health status of the farms ranged from 32.38% to 96.40% according to disease positivity. The animal health status value will have a direct reflection on the production chain both on and off the farm, providing not only great market advantages, due to how the expression of animal health will add value to livestock farms, as well as on the consumer who can check the quality of animal health at the beginning of the production chain.

Leishmaniose visceral e o sistema nervoso central: inflamação nas infecções natural canina e experimental em camundongos: Guilherme Dias de Melo. -

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