Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2.

Obesity is widely recognized as cause of metabolic syndrome and cardiovascular disease. It is provoked by imbalance between the spending and consumption of energy associated with a chronic inflammatory condition due to excessive storage of fat tissue. Obese patients have an impaired inflammatory profile that contributes to the development of vascular complications, with fat tissue being partially responsible for controlling both processes: energy balance (through PPAR) and inflammatory condition (through inflammatory markers). White adipose tissue produces cytokines (IL-6, TNF-α, resistin, adiponectin, etc.) and participates in a broad spectrum of processes. Recently, glycine has been reported to have anti-inflammatory properties which reduce TNF-α and IL-6 levels and increase adiponectin in 3T3-L1 adipocytes and in fat tissue of obese mice. In this study, the possible regulatory role of glycine on some factors involved in storage and energy burning (PPAR-γ, PPAR-α, PPAR-δ and UCP-2) was analyzed in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Glycine clearly increased fat tissue PPAR-γ expression in lean but not in MSG/Ob mice. The PPAR-γ and PPAR-α liver expression was repressed in both groups of mice, while the expression of PPAR-δ decreased only in lean mice. Interestingly, glycine treatment also suppressed the expression of UCP-2, TNF-α and IL-6 in lean mice, and increased adiponectin and insulin serum levels. In conclusion, glycine regulates the production of inflammatory cytokines through PPAR-γ. These results provide clues on glycine signaling mechanisms as an anti-inflammatory agent that might be useful for treatment of metabolic and vascular complications associated to inflammation in obesity.

Evaluation of the hypoglycemic effect of Cucurbita ficifolia Bouché (Cucurbitaceae) in different experimental models.

Acute hypoglycemic effects of freeze-dried juice of Cucurbita ficifolia Bouché (Cucurbitaceae) fruits were studied in healthy and alloxan-diabetic mice. C. ficifolia fruit administered by intraperitoneal route produced, in a dose-dependent manner, a significant decrease of the glycemia in healthy mice. Although oral route of C. ficifolia fruit juice also caused significant reductions of blood glucose levels in healthy mice, the effect was minor. The juice administered by intraperitoneal route showed an acute hypoglycemic effect in alloxan-diabetic mice. In addition, daily oral administration of this preparation showed a highly significant reduction of the glycemia after 14 days of treatment. Freeze- dried juice caused acute toxicity when administered intraperitoneally, and also when it was administered daily by the oral route.

Bioavailability of two oral formulations of cyclosporin A in uremic children before renal transplantation.

The bioavailability of two oral formulations of cyclosporin A (Sandimmun and Neoral) was assessed in 10 children with end-stage renal disease (ESRD), while at a steady state on a dialytic procedure. The study was performed according to a randomized, double blind, cross-over design, allowing a 1-month washout period between studies. Each patient received 2.5 mg/microg of oral cyclosporin A every 12 h, either Sandimmun (SAN) or Neoral (NEO). Serum concentrations of cyclosporin A were determined serially during a 24 h period, after the 5th dose of cylosporin. Serum concentrations against time curves were constructed and bioavailability of both medications, expressed as AUC and Cmax, were compared. A statistically significant increase was observed in the AUC and Cmax of NEO, which were 90% and 130% higher, respectively, than those of SAN. Considering that the internationally accepted criteria for bioequivalence allows a 20% variation in AUC and Cmax, it appears that Neoral and Sandimmun do not bear bioequivalence in children with ESRD. Notwithstanding, there were no significant differences in trough levels between both formulations. We conclude that, if trough levels are the only source of information for dosing design, Neoral could be substituted for Sandimmun on a 1:1 basis. However, a 1:1 drug substitution is not suitable when AUC is used in children with ESRD.