A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children

Submitted by Nuzia Santos ([email protected]) on 2015-04-30T16:43:26Z No. of bitstreams: 1 2014_198.pdf: 159307 bytes, checksum: fd184d5598daf80e1d8ade4e11ecd865 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-30T16:51:38Z (GMT) No. of bitstreams: 1 2014_198.pdf: 159307 bytes, checksum: fd184d5598daf80e1d8ade4e11ecd865 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-30T16:55:38Z (GMT) No. of bitstreams: 1 2014_198.pdf: 159307 bytes, checksum: fd184d5598daf80e1d8ade4e11ecd865 (MD5)Made available in DSpace on 2015-04-30T16:55:38Z (GMT). No. of bitstreams: 1 2014_198.pdf: 159307 bytes, checksum: fd184d5598daf80e1d8ade4e11ecd865 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, Brazil.Universidade Federal de São Paulo. Departamento de Fisiobiologia. São Paulo, SP, Brazil.Fundação Hospitalar de Minas Gerais. Hospital Infantil João Paulo II. Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo. Departamento de Fisiobiologia. São Paulo, SP, Brazil.Background: Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals. Methods: Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011. Results: We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters. Conclusions: Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

Submitted by sandra infurna ([email protected]) on 2016-03-10T14:47:14Z No. of bitstreams: 1 alex_chapeaurouge_etal_IOC_2015.pdf: 343462 bytes, checksum: deaf5a5bf883dc052b8cdda7882ad5b1 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-03-10T15:07:20Z (GMT) No. of bitstreams: 1 alex_chapeaurouge_etal_IOC_2015.pdf: 343462 bytes, checksum: deaf5a5bf883dc052b8cdda7882ad5b1 (MD5)Made available in DSpace on 2016-03-10T15:07:20Z (GMT). No. of bitstreams: 1 alex_chapeaurouge_etal_IOC_2015.pdf: 343462 bytes, checksum: deaf5a5bf883dc052b8cdda7882ad5b1 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou (CPqRR). Grupo de Pesquisa em Genômica e Biologia Computacional. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou (CPqRR). Grupo de Pesquisa em Genômica e Biologia Computacional. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou (CPqRR). Grupo de Pesquisa em Genômica e Biologia Computacional. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou (CPqRR). Grupo de Pesquisa em Genômica e Biologia Computacional. Belo Horizonte, MG, Brasil.FHEMIG. Hospital de Crianças João Paulo II. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou (CPqRR). Grupo de Pesquisa Informática de Biosistemas. Belo Horizonte, MG, Brasil.Background: Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. Methods: We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Results: Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Conclusions: Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis

Meningitis Associated with Simultaneous Infection by Multiple Dengue Virus Serotypes in Children, Brazil

To determine the causes of viral meningitis, we analyzed 22 cerebrospinal fluid samples collected during the 2014–2015 dengue epidemics in Brazil. We identified 3 serotypes of dengue virus (DENV-1, -2, and -3), as well as co-infection with 2 or 3 serotypes. We also detected the Asian II genotype of DENV-2