BackgroundLeptospiral glycolipoprotein (GLP) is a potent and specific Na/K-ATPase inhibitor. Severe pulmonary form of leptospirosis is characterized by edema, inflammation and intra-alveolar hemorrhage having a dismal prognosis. Resolution of edema and inflammation determines the outcome of lung injury. Na/K-ATPase activity is responsible for edema clearance. This enzyme works as a cell receptor that triggers activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therefore, injection of GLP into lungs induces injury by triggering inflammation.MethodsWe injected GLP and ouabain, into mice lungs and compared their effects. Bronchoalveolar lavage fluid (BALF) was collected for cell and lipid body counting and measurement of protein and lipid mediators (PGE2 and LTB4). The levels of the IL-6, TNFα, IL-1B and MIP-1α were also quantified. Lung images illustrate the injury and whole-body plethysmography was performed to assay lung function. We used Toll-like receptor 4 (TLR4) knockout mice to evaluate leptospiral GLP-induced lung injury. Na/K-ATPase activity was determined in lung cells by nonradioactive rubidium incorporation. We analyzed MAPK p38 activation in lung and in epithelial and endothelial cells.ResultsLeptospiral GLP and ouabain induced lung edema, cell migration and activation, production of lipid mediators and cytokines and hemorrhage. They induced lung function alterations and inhibited rubidium incorporation. Using TLR4 knockout mice, we showed that the GLP action was not dependent on TLR4 activation. GLP activated of p38 and enhanced cytokine production in cell cultures which was reversed by a selective p38 inhibitor.ConclusionsGLP and ouabain induced lung injury, as evidenced by increased lung inflammation and hemorrhage. To our knowledge, this is the first report showing GLP induces lung injury. GLP and ouabain are Na/K-ATPase targets, triggering intracellular signaling pathways. We showed p38 activation by GLP-induced lung injury, which was may be linked to Na/K-ATPase inhibition. Lung inflammation induced by GLP was not dependent on TLR4 activation.

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, many cases of hepatitis A were notified in the county of Belford Roxo involving individuals aged 0 to 79 years. Serum samples were collected to evaluate the prevalence of anti-hepatitis A virus (HAV) antibodies, to detect HAV-RNA and to correlate with possible risk factors of HAV infection. Serum samples were screened by commercial IgM and total anti-HAV antibody ELISA and HAV-RNA was isolated and subsequently amplified by reverse transcription-polymerase chain reaction (RT-PCR) at VP1/2A region, and Key words: hepatitis A virus -molecular epidemiology -co-circulation of subgenotypes IA and IB Hepatitis A virus (HAV) is an RNA virus that is transmitted mainly by fecal oral route and is the only member of the genus Hepatovirus of the Picornaviridae family (Melnick 1982(Melnick , 1992. Studies on nucleic acid heterogeneity of HAV strains, in VP1/2A junction, characterize and group isolates in six different genotypes (I-VI) and six sub-genotypes (IA, IB, IIA, IIB, IIIA, and IIIB) (Robertson et al. 1992. Genotypes are distinguished by 15-25% sequence diversity, whereas sub-genotypes in each genotype differ in about 7.5% of base positions (Robertson et al. 1992). Comparison among nucleotide sequences allows genetically relating different strains during an outbreak and providing new insights into the molecular epidemiology of HAV.HAV is the main cause for acute viral hepatitis which represents a significant public health problem worldwide. However, a progressive decline in hepatitis A mortality rate could be seen in all Brazilian regions, being observed a rate of 0.2/100,000 inhabitants in 1980 to the rate of 0.02/100,000 inhabitants in (Vitral et al. 1998. The incidence of hepatitis A in Brazil has markedly decreased as showed by Vitral et al. (1998) 98.1 to 7.8% among children under the age of five in two different populations of low socioeconomic status in Rio de Janeiro, a city located in the Southeastern region (Vitral et al. 1998). This phenomenon can probably be attributed to improvements in sanitary conditions. If this hypothesis is true, then the transmission route of HAV in Brazil may have changed within time. Studying changes in HAV transmission routes in Brazil may therefore elucidate the influence of sanitation on transmission routes. Molecular epidemiological approaches may also be useful for studying transmission routes and provide new information for the control of this disease. Studies carried out in Brazil have shown that two subgenotypes circulate in our country and strains isolated from the same region demonstrated close genetic relatedness , Villar et al. 2004. In this study, we have analyzed the molecular and epidemiological relationship between HAV isolates recovered from acute cases notified in communities of surrounding region of Rio de Janeiro sampled from 1999 to 2001. PATIENTS, MATERIALS AND METHODSPopulation study -The county of Belfor Roxo covers 30 Km Northwest of the city of Rio de Janeiro with a population of approximately 435.000 inhabitants. This city is subdivided in five distri...

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