Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat

The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the administration of agonists and antagonists of the ionotropic and metabotropic glutamate receptors within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon stimulation of metabotropic glutamate receptors, but results from activation of (NMDA) receptors, (2) the cytotoxicity of quisqualate to cholinergic cells within the NBM is not dependent upon stimulation of NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg), resulting in plasma levels of 2.5 μg/ml, a concentration known to block efficiently NMDA receptors in vitro. Finally, performance of a food-motivated, delayed-alternation task on a T-maze was impaired by injections of NMDA into the NBM, but was prevented by co-administration of NMDA with memantine.     

The activity of erythrocyte sodium-proton exchanger in women with pregnancy- induced hypertension.

BACKGROUND: Hypertension that develops after 20 gestational weeks and is defined as pregnancy-induced hypertension (PIH). The main cause of PIH is vasoconstriction and the thickening of vascular media, which decreases vascular capacity and increases peripheral resistance. One of the theories postulated to explain this phenomenon is that a transmembrane sodium transport disorder causes an increase in intracellular sodium concentration. In the latest literature, special attention is paid to the role of the increased intracellular sodium concentration in the pathogenesis of essential hypertension (EH). One of the best documented phenotypes for EH is the increased activity of the sodium-proton exchanger (NHE). The aim of this study was to assess if increased NHE activity could be the mechanism responsible for the development of PIH. SUBJECTS AND METHODS: The study included 30 women: 10 pregnant women with PIH after gestational week 30, 10 women with physiological pregnancy after 30 gestational weeks, and 10 healthy non-pregnant women. NHE activity was determined according to Orlov's method as amiloride-sensitive H(+) efflux from acid-loaded cells. RESULTS: The NHE activity in the group of women with PIH was significantly higher than that in women with physiological pregnancy: 10.09 +/- 1.65 vs. 6.81 +/- 2.3 mmol/L RBC/h (p < 0.049) and in the group of non-pregnant women: 10.09 +/- 1.65 vs. 7.56 +/- 1.66 mmol/L RBC/h (p < 0.029). Erythrocyte NHE activity did not differ in the group of women with physiological pregnancy and in the group of non-pregnant women. CONCLUSION: These results seem to suggest that erythrocyte NHE activity is elevated in PIH pregnancies.     

Pharmacokinetics of phenazone after bilateral ovariectomy in female rabbits]

The aim of this study was to evaluate the influence of female sex hormones on phenazone pharmacokinetics using as an experimental model female rabbits after a bilateral ovariectomy. Eighteen female rabbits divided into two groups: control animals and experimental rabbits, that underwent ovariectomy, were used in the study. Pharmacokinetic assays were performed in all animals: prior to the study, after 1 month and after 2 months. Blood was sampled within 24 hours after intragastric administration of phenazone at a dose 50 mg/kg b.w. Two compartment open model was used for calculations. Significant increase in AUC and prolongation of phenazone halflife as well as a decrease in the total body clearance were noted. The study demonstrated the possible inhibition of the microsomal mixed-function oxidase system by oestrogens.     

Solvent effects on free-radical polymerization, 5. Analysis of homopolymerization rate on the basis of the reactant-solvent complex model

The rate of polymerization was described as a function of the monomer concentration of 36 monomer/solvent systems in terms of the reactant-solvent complex (RSC) model. One-, two-and three-parameter optimization procedures were used to fit the rate function to experimental data. Fitting increments were the complex equilibrium constant K and the relative monomer reactivity parameter r₁₁. Irrespective of the optimization procedure, K and r₁₁, were found to correlate with the monomer exponent n and to be K = 0 and r₁₁, = 1 at n = 1. In these cases the RSC model reduces to the classical rate model. Despite the weak character of the monomer (radical)/solvent complexation, this interaction should not be neglected in rate modelling. The RSC model is a convenient tool to describe the chain propagation separately.     

Development of a multiplex ARMS test for mutations in the HFE gene associated with hereditary haemochromatosis.

Genetic testing for hereditary haemochromatosis is likely to be a significant workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE gene associated with hereditary haemochromatosis have previously been detected using a number of methods including alterations in the restriction digest pattern of polymerase chain reaction (PCR) amplified products. An amplification refractory mutation system (ARMS) has been developed that will simultaneously detect both hereditary haemochromatosis mutations. Comparison of the results obtained from the analysis of 46 samples referred for hereditary haemochromatosis testing showed no discrepancies between ARMS and restriction enzyme digestion. Furthermore, consistent results were obtained by ARMS from both blood and buccal mouthwash samples. The ARMS test is quicker and less expensive in terms of consumables and scientist time than restriction enzyme analysis, and is therefore suited to the routine diagnostic analysis of hereditary haemochromatosis.