Sepsis, the leading cause of death in intensive care units, is associated with overproduction of nitric oxide (NO) due to inducible NO synthase (iNOS), responsible for some of the pathologic changes. Aminoguanidine (AG) is a selective iNOS inhibitor with reported inconsistent actions in sepsis. To investigate the influence of iNOS, we studied models of acute bacterial sepsis using acute challenges with aerobic (Escherichia coli) and anaerobic (Bacteroides fragilis) bacteria in the presence of AG. Six-week-old, 23 g, male and female BALB/c and C57Bl/6j mice, in equal proportions, were inoculated (ip) with bacteria in groups of 4 animals for each dose and each experiment in the absence or presence of AG (50 mg/kg, ip, starting 24 h before challenge and daily until day 6) and serum nitrate was measured by chemiluminescence. Both types of bacteria were lethal to mice, with an LD50 of 6 nephelometric units (U) for E. coli and 8 U for B. fragilis. Nitrate production peaked on the second day after E. coli inoculation with 8 and 6 U (P < 0.05), but was absent after non-lethal lower doses. After challenge with B. fragilis this early peak occurred at all tested doses after 24 h, including non-lethal ones (P < 0.05). AG-treated mice challenged with E. coli presented higher survival (P < 0.05) and increased LD50. AG-treated mice challenged with B. fragilis had lower LD50 and higher mortality. Control AG-treated animals presented no toxic effects. The opposite effect of iNOS blockade by AG in these models could be explained by restriction of oxygen for immune cells or an efficient action of NO in anaerobic localized infections. The antagonic role of NO production observed in our bacterial models could explain the reported discrepancy of NO action in sepsis.

Toxoplasmose é uma infecção zoonótica humana de alta prevalência, causada por um protozoário Apicomplexa, Toxoplasma gondii. A evolução da doença aguda é geralmente leve ou assintomática, exceto nas infecções agudas das gestantes, quando a infecção fetal causa uma doença devastadora. Para determinar se haveriam fatores de risco regionais, foi analisada a frequência de títulos de anticorpos anti-T.gondii em áreas na região Metropolitana de São Paulo, comparando grupos etários. Esta frequência de soronegatividade foi determinada retrospectivamente em 1286 gestantes que procuraram os serviços públicos para exames pré-natais da região metropolitana de São Paulo, usando um teste de imunofluorescência indireta para IgG anti-T. gondii, em quatro áreas selecionadas, com infraestrutura e condições sociais semelhantes. A área da cidade de São Paulo apresentou a maior frequência de soronegatividade (41,1%), seguida pelas áreas Noroeste (31,5%) e Sudoeste(29,9%), com níveis intermediários semelhantes, e a área Nordeste (22,5%), com a menor frequência (p<0,001). Uma estimativa grosseira permite estimar em cerca de 280 crianças infectadas por ano na Região Metropolitana de São Paulo. A análise dos títulos sorológicos por grupos etários sugere uma queda de seus valores com a idade, mostrada pela menor frequência de títulos elevados em grupos de maior idade. Este estudo enfatiza a importância da determinação da prevalência regional de toxoplasmose, para dimensionar adequadamente os serviços e cuidados de saúde pré-natal, na rede pública.

Toxoplasmosis is a highly prevalent zoonotic human infection caused by the Apicomplexa protozoon Toxoplasma gondii. The acute disease is usually mild or asymptomatic, except for foetal infection transmitted by acutely infected pregnant women, which courses as a devastating disease. In order to determine possible regional variations in risk factors, we studied the frequency of seronegativity in areas of the São Paulo Metropolitan Region, comparing liters and age groups. The prevalence of seronegativity was determined retrospectively in 1286 pregnant women receiving prenatal care at public health services in four selected areas of the São Paulo Metropolitan Region of similar socioeconomic background. The São Paulo City area had the higher frequency of seronegativity (41.1%), followed by the Northwest (31.5%) and Southwest (29.9%) areas, with similar intermediate levels, and by the Northeast (22.5%) area with the lowest frequency (p<0.001). A rough estimate disclosed about 280 infected infants/year in the São Paulo Metropolitan Region. Serological titers analyzed by age group suggested a decline in antibody levels with age, as shown by a lower frequency of higher titers in older groups. Our study emphasizes the importance of determining the regional prevalence of toxoplasmosis for proper planning of public health prenatal care.