RESUMEN
Streptococcus pneumoniae infections of the lung are associated with significant damage to the alveolar epithelium. Host phagocytes and pneumolysin, a cytolytic toxin of S. pneumoniae, are believed to contribute to this cellular damage, yet experiments in which these elements are absent demonstrate the presence of an additional soluble S. pneumoniae factor that is toxic to alveolar epithelium. We examined the effects of S. pneumoniae-associated alveolar epithelial cell injury by factors other than S. pneumoniae-derived pneumolysin or phagocyte products by exposing cultured rat type II alveolar epithelial cells (RAEC) to S. pneumoniae mutants that lacked pneumolysin activity. We found that mutant pneumolysin-deficient strains of S. pneumoniae produced injury to RAEC similar to that produced by the parent strains. A toxin of type 14 S. pneumoniae was distinguished from pneumolysin by physiochemical (i.e., molecular mass and heat stability) and functional (i.e., hemolytic activity and cytotoxic activity) properties and was identified as hydrogen peroxide. All S. pneumoniae strains tested produced hydrogen peroxide, and in many strains hydrogen peroxide production was comparable to that of activated neutrophils. We conclude that S. pneumoniae produces hydrogen peroxide in concentrations that are cytotoxic to RAEC in vitro and that alveolar epithelial damage due to hydrogen peroxide may be involved in the pathogenesis of host cellular injury in pneumococcal pneumonia.
Asunto(s)
Toxinas Bacterianas , Peróxido de Hidrógeno/metabolismo , Alveolos Pulmonares/efectos de los fármacos , Streptococcus pneumoniae/patogenicidad , Animales , Supervivencia Celular , Células Cultivadas , Hemólisis , Peróxido de Hidrógeno/toxicidad , Técnicas In Vitro , Neumonía Neumocócica/microbiología , Neumonía Neumocócica/patología , RatasRESUMEN
BACKGROUND AND METHODS: Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet--low total energy expenditure and underreporting of caloric intake--in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. RESULTS: Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic effects of food and exercise. Low energy expenditure was thus excluded as a mechanism of self-reported diet resistance. In contrast, the subjects in group 1 underreported their actual food intake by an average (+/- SD) of 47 +/- 16 percent and overreported their physical activity by 51 +/- 75 percent. Although the subjects in group 1 had no distinct psychopathologic characteristics, they perceived a genetic cause for their obesity, used thyroid medication at a high frequency, and described their eating behavior as relatively normal (all P < 0.05 as compared with group 2). CONCLUSIONS: The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis.