Mice (BDF(1)) inoculated with L1210 leukemia survive for a statistically significantly longer span when four courses of arabinosyl cytosine are administered at 4-day intervals-not in courses consisting of eight equal doses at 3-hour intervals, but in sinusoidally increasing and decreasing 24-hour courses, the largest amount being given at previously mapped circadian and circannual times of peak host resistance to the drug. This finding relates to the many therapeutic situations involving rhythmic, and thus predictable, cycles in the host's tolerance of undesired effects from the agent used.
Conventional vaccines to prevent the pneumonia caused by Rhodococcus equi have not been successful. We have recently demonstrated that immunization with Salmonella enterica Typhimurium expressing the VapA antigen protects mice against R. equi infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the in vitro stimulation with R. equi antigen. After in vitro stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following R. equi challenge, a high H2O2, NO, IL-12, and IFN-γ content is detected in the organs of immunized mice. On the other hand, TNF-α and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-β are also higher in the organs of immunized mice. A greater incidence of CD4+ and CD8+ T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4+CD25+Foxp3+ T cells. Finally, we show that the vaccination confers a long-term protection against R. equi infection. Altogether, these data indicate that the oral vaccination of mice with S. enterica Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.
Gastroparesis causes gastric emptying disorders in patients with chronic diabetes mellitus and it results from reduced smooth muscle contractility secondary to autonomic dysfunction. Today there has been little objective evidence of improvement in gastric emptying following correction of both uremia and diabetes by combined kidney-pancreas transplantation. We used gastrointestinal symptom scores, solid gastric emptying tests and electrogastrography to evaluate the effect of combined kidney-pancreas transplantation on gastric emptying in 8 uremic diabetic patients. The mean age of the patients was 40 years (range: 30–51 years) and the mean duration of diabetes was 24 years (range: 16–30 years). The patients had been on dialysis up to 24 months. The pretransplant Al mean was 6.5 before improving to 4.3 after transplantation. All patients were receiving exogenous insulin. Our study data indicate that uremic diabetics have a high prevalence of symptomatic gastrointestinal dysfunction including abnormalities of gastric emptying and gastric electrical activity. Following transplantation, the gastrointestinal symptomatology improved significantly. Significant improvement in the rate of gastric emptying also correlated with improvement in the symptom complex. Gastric electrical activity also improved during the follow-up period.
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