Advanced glycation end products in hemodialyzed patients with diabetes mellitus correlate with leptin and leptin/body fat ratio.

Advanced glycation end products (AGEs) and other carbonyl and oxidative stress compounds are supposed to play a critical role in the pathogenesis of several diseases and their complications, i.e., diabetes mellitus, diabetic retinopathy, atherosclerosis, and chronic renal failure. In the present investigation, we were interested in the relationship of AGEs in plasma to other prominent factors in the patients on chronic hemodialysis treatment-27 patients with diabetes mellitus, 35 patients without diabetes mellitus. AGE-group reactivity was estimated using a spectrofluorometric method (excitation 350 nm, emission 430 nm) and is expressed in arbitrary units (AU). We found significantly higher AGEs levels in diabetics than in non-diabetics on regular hemodialysis treatment both before (2.7 +/- 0.7 x 10(4) AU vs. 2.2 +/- 0.6 x 10(4) AU, p < 0.001) and after the dialysis session (2.3 +/- 0.5 x 10(4) AU vs. 1.8 +/- 0.7 x 10(4) AU, p < 0.005). AGEs were significantly reduced during hemodialysis in both groups of patients--by 15.4% in the diabetic go (p < 0.001) and by 17.3% in non-diabetics (p < 0.005). In the patients with diabetes mellitus, AGEs did not correlate with parameters of the glucose metabolism correction (blood glucose, HbA1c). We observed a significant correlation between AGEs and leptin (r = 0.48, p < 0.05) as well as the leptin/body fat ratio (r = 0.56, p < 0.05) only in hemodialyzed patients with diabetes mellitus. These findings suggest more detailed studies to identify the molecular links between carbonyl stress, i.e., advanced glycation end products, and leptin metabolism, sign of microinflammation and hypertension.

Dose-dependent disposition kinetics and tissue accumulation of boron after intravenous injections of sodium mercaptoundecahydrododecaborate in rabbits.

Kinetics of boron disposition after single intravenous injections of two different doses (25 and 50 mg/kg) of mercaptoundecahydrododecaborate sodium (Na2B12H11SH; BSH) was studied in rabbits. Residual boron concentrations in various organs and tissues (heart, lungs, liver, spleen, kidney, adrenals, and brain) were also determined after seven daily injections of the same doses of BSH. Boron blood and tissue concentrations were measured by atomic emission spectrometry. In the majority of animals, the decline of boron blood concentrations after a single intravenous injection of either dose was biphasic, being consistent with a two-compartment model of boron disposition in the body. Although mean boron blood concentrations were roughly proportional to the BSH dose delivered, the mean total body clearance of boron from the body was 3 times lower (6.5 +/- 1.9 ml min-1 kg-1) after a dose of 50 mg/kg than after the injection of 25 mg/kg (22.4 +/- 7.9 ml min-1 kg-1), the difference between the means being statistically significant (P less than 0.05). Moreover, the mean terminal half-life of boron in blood was prolonged after the injection of 50 mg/kg (14.5 +/- 5.5 h) as compared with that found after the 25-mg/kg dose (3.5 +/- 0.9 h). On the other hand, the different BSH doses did not result in marked differences in the mean values obtained for the volume parameters - the volume of the central compartment (1.3 +/- 0.4 vs 1.3 +/- 0.5 l kg-1) and the volume of distribution at steady state (4.7 +/- 1.3 vs 6.0 +/- 4.0 l kg-1) - both of which were high, indicating extensive binding of the compound not only in the blood but also in tissues. Residual concentrations of boron found after seven daily injections of both doses of BSH were highest in the kidneys, the difference in the mean values being relatively small (33.6 +/- 6.1 vs 39.0 +/- 10.7 micrograms/g tissue). In the majority of other organs (heart, lung, liver, spleen, brain, adrenals), the residual concentrations after a dose of 50 mg/kg were disproportionately higher than those measured after the injection of 25 mg/kg, and the mean values corresponded to the reduced total body clearance rather than to the increased BSH dose. The saturability of BSH binding to blood and tissue proteins is suggested as a possible explanation for the dose dependency of the total clearance of boron from the body and the accumulation of BSH in organs and tissues.