RESUMEN
Coinfection can markedly alter the response to a pathogen, thereby changing its clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are associated with gastroenteritis in immunocompetent individuals. In contrast, individuals with severe pediatric malaria can develop bacteremic infections with NTS, during which symptoms of gastroenteritis are commonly absent. Here we report that, in both a ligated ileal loop model and a mouse colitis model, malaria parasites caused a global suppression of gut inflammatory responses and blunted the neutrophil influx that is characteristic of NTS infection. Further, malaria parasite infection led to increased recovery of Salmonella enterica serotype Typhimurium from the draining mesenteric lymph node (MLN) of mice. In the mouse colitis model, blunted intestinal inflammation during NTS infection was independent of anemia but instead required parasite-induced synthesis of interleukin (IL)-10. Blocking of IL-10 in coinfected mice reduced dissemination of S. Typhimurium to the MLN, suggesting that induction of IL-10 contributes to development of disseminated infection. Thus IL-10 produced during the immune response to malaria in this model contributes to suppression of mucosal inflammatory responses to invasive NTS, which may contribute to differences in the clinical presentation of NTS infection in the setting of malaria.
Asunto(s)
Inmunidad Mucosa , Interleucina-10/inmunología , Malaria/inmunología , Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Animales , Femenino , Interleucina-10/genética , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Macaca mulatta , Malaria/genética , Malaria/patología , Mesenterio/inmunología , Mesenterio/microbiología , Mesenterio/patología , Ratones , Ratones Noqueados , Infecciones por Salmonella/genética , Infecciones por Salmonella/patologíaRESUMEN
Characterizing components eluting from a HPLC column is enhanced when multiple detectors are incorporated in-line. The performance of a system consisting of a combination of two detectors-electrospray ionization mass spectrometry (and tandem mass spectrometry) and radioactivity monitoring, following gradient separation with a 250 x 2.1 mm I.D. (Vydac Protein and Peptide C18, 5 microns, 300 A) column-is evaluated with respect to chromatographic integrity and detection. The HPLC effluent was split (8:1) and a post-column make-up solvent was added to flow directed towards the radioactivity detector containing a solid glass cell. Trifluoracetic acid (0.1%) was added to the make-up flow solvent to prevent silanol interactions from degrading the profile displayed in the 14C trace. A 14C chromatographic peak representing 550 dpm was detected with signal-to-noise ratio of 3. This system was used for rapidly characterizing the biliary metabolites of an arginine fluoroalkyl ketone analog of D-MePhe-Pro-Arg, a potent thrombin inhibitor currently being evaluated as a drug candidate. These metabolites are shown to comprise of mono- and dihydroxylated drug as well as a reduced ketone form of the drug. Combining the radioactivity monitor in-line with the mass spectrometer ensured that all of the major metabolites (as evident from the 14C profile) were characterized by mass spectrometry.
Asunto(s)
Clorometilcetonas de Aminoácidos/análisis , Bilis/química , Oligopéptidos/análisis , Trombina/antagonistas & inhibidores , Clorometilcetonas de Aminoácidos/metabolismo , Animales , Bilis/metabolismo , Radioisótopos de Carbono , Cromatografía Líquida de Alta Presión/métodos , Masculino , Espectrometría de Masas , Ratas , Ratas Sprague-DawleyRESUMEN
This study evaluated the relationship between Marlatt and Gordon's (1985) Abstinence Violation Effect (AVE) and fasting outcomes of patients enrolled in a Very Low Calorie Diet (VLCD) and behavior education program. Within the first 11 weeks of the VLCD, 41 of 76 patients reported a fasting lapse and rated this lapse on an attribution scale. Patients reporting greater characterological attributions for their first lapse (i.e., a higher AVE) lost a smaller percentage of their excess weight during active fasting than patients reporting more situational attributions r(39) = -.36, p less than .025. First lapse AVE ratings did not distinguish between program dropout versus completer status, but high AVE dropouts did spend fewer weeks in the VLCD program than low AVE dropouts, r(12) = -.54, p less than .05. Although a faster's initial level of obesity accounted for the largest portion of weight loss outcome variance, the AVE accounted for a significant additional portion of outcome.