IMMUNOLOGICAL EVALUATION OF PATIENTS WITH TYPE 2 DIABETES MELLITUS SUBMITTED TO METABOLIC SURGERY

Background :

Immunological and inflammatory mechanisms play a key role in the development and progression of type 2 diabetes mellitus.

Aim :

To raise the hypothesis that alterations in immunological parameters occur after duodenojejunal bypass surgery combined with ileal interposition without gastrectomy, and influences the insulin metabolism of betacells.

Methods :

Seventeen patients with type 2 diabetes mellitus under clinical management were submitted to surgery and blood samples were collected before and six months after surgery for evaluation of the serum profile of proinflammatory (IFN-γ, TNF-α, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10). In addition, anthropometric measures, glucose levels and insulin use were evaluated in each patient.

Results :

No changes in the expression pattern of proinflammatory cytokines were observed before and after surgery. In contrast, there was a significant decrease in IL-10 expression, which coincided with a reduction in the daily insulin dose, glycemic index, and BMI of the patients. Early presentation of food to the ileum may have induced the production of incretins such as GLP-1 and PYY which, together with glycemic control, contributed to weight loss, diabetes remission and the consequent good surgical prognosis of these patients. In addition, the control of metabolic syndrome was responsible for the reduction of IL-10 expression in these patients.

Conclusion :

These findings suggest the presence of low-grade inflammation in these patients during the postoperative period, certainly as a result of adequate glycemic control and absence of obesity, contributing to a good outcome of surgery.     

Postexercise blood pressure reduction in elderly hypertensive patients

OBJECTIVES: We sought to study: 1) the impact of hemodynamic and left ventricular function on short-term postexercise blood pressure reduction in elderly hypertensive patients; and 2) the 22-h postexercise effects on ambulatory blood pressure in elderly hypertensive patients. BACKGROUND: Although early exercise provokes postexercise blood pressure reduction, the mechanisms underlying this response are not completely understood. Besides, it is unclear whether the reduction in blood pressure after exercise lasts long enough to have clinical relevance in elderly hypertensive patients. METHODS: We studied 24 elderly hypertensive patients (age 68.9 +/- 1.5 years) and 18 age-matched normotensive control subjects (age 68.1 +/- 1.2 years). Cardiac output (carbon dioxide rebreathing) and blood pressure (auscultatory) were measured at rest and after a 45-min period of low-intensity bicycle exercise (50% maximal oxygen uptake) and at 15, 30, 60 and 90 min after exercise. Left ventricular function (by Doppler echocardiography) was also evaluated. Ambulatory blood pressure monitoring was evaluated after 45 min of exercise or 45 min of rest, in a randomized order. RESULTS: In the hypertensive patients, exercise provoked a significant reduction in blood pressure, cardiac output, stroke volume and left ventricular end-diastolic volume. It also provoked a significant reduction in systolic, mean and diastolic blood pressure during a 22-h period, at daytime and nighttime. CONCLUSIONS: The short-term reduction in blood pressure after exercise in elderly hypertensive patients is associated with a decrease in stroke volume and left ventricular end-diastolic volume. The 22-h postexercise reduction in blood pressure demonstrates the clinical relevance of low-intensity exercise in elderly hypertensive patients.     

In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.     

Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii

Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of C. gattii by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of C. gattii. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.