Biomedica biochimica acta最新文献

Administration of stobadine, a cardioprotective substance in investigation prevents a decrease in the content of protein SH groups and glutathione in hearts of rats treated with high doses of isoproterenol (ISO) (30 mg/kg). Moreover, stobadine also attenuated the increase in the content of malondialdehyde and activities of catalase and glutathione reductase as well as a diminution in the GSH/GSSG ratio observed in heart mitochondria isolated from ISO-treated animals. Since stobadine may be considered as a scavenger of reactive oxygen species (ROS), the above effects of the latter substance support the assumption about a possible involvement of reactive oxygen species (ROS) in some processes initiated by administration of ISO in doses inducing cardiac hypertrophy. However our results also indicate that ROS-mediated processes are not necessarily involved in the mechanism of induction of cardiac hypertrophy itself.

A new method for the preparation of a neoglycoprotein (chemically mannosylated bovine serum albumin, D-Man.BSA) is described using the homobifunctional reagent divinylsulphone.D-Man.BSA purified by affinity chromatography on ConA-Sepharose 4B shows microheterogeneity as demonstrated by immunoaffinity electrophoresis with free ConA in the first-dimension gel. The dissociation constant K for the neoglycoprotein-ConA complex has been calculated to be 2.5.10(-5) M. Biotinylated D-Man.BSA is a useful reagent to detect carbohydrate binding proteins of L1210 leukemia cells on blots. The neoglycoprotein labelled with colloidal gold may be used to demonstrate L1210 cell surface D-Man binding proteins by preembedding electron microscopy.

Long-Evans hooded rats were not able neither to reach criterion of active avoidance tasks in a Y-maze and in a jump test, nor in brightness discrimination after lesions of the NRTP without preoperative experience in these tests. After preoperative consolidation of active avoidance, the retention of Y-maze avoidance performance was zero and of jump test avoidance at 25%. The Y-maze avoidance was again relearned except in the task with 2:2 alternation of goals whereas retention of brightness discrimination was not affected. In the jump test, avoidance relearning was evidently retarded. Ambulatory and exploratory behaviour in the open field were significantly reduced after NRTP lesions. The NRTP is evidently involved in the establishment and control of goal-directed behaviour.

Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.

Pharmacokinetic studies with the arterial chemoreceptor stimulant almitrine (100 mg per os) were performed in 12 healthy volunteers and 8 patients with essential hypertension stage I in order to evaluate the suitability of the drug for physiological tests. The parent compound was determined gas-chromatographically. Almitrine was absorbed with maximal serum levels after 1.8 +/- 0.4 h in healthy volunteers and 1.5 +/- 0.3 h in patients. The elimination proceeded biexponentially with terminal half-lives from 14.6 to 43.4 h in volunteers and 12.5-45.0 h in patients. Further characteristics were large distribution volumes (16.1 +/- 4.5 ml/g in healthy volunteers, 13.9 +/- 4.7 ml/g in patients) and large interindividual variations of all pharmacokinetic parameters by a factor of 2 to 6. Significant differences between healthy individuals and patients were not observed. The drug was well tolerated. The pharmacokinetic properties of almitrine should be included into its evaluation as a test compound.

The S'-subsite specificity of the endoproteinase Glu/Asp-C from Actinomyces sp. was studied by acyl transfer reactions using amino-acid- and peptide-derived nucleophilic amino components. The following results were obtained: 1. The enzyme prefers amino acid amides with hydrophobic side chains in P'i position. In addition, positively charged functions in this position favour S'-P' interactions significantly. 2. Stereospecific binding is a prerequisite for nucleophilic efficiency. 3. Dipeptide amides are more efficient amino components in comparison to free dipeptides whereas oligoglycines show a poor nucleophilic behaviour independent of chain length.

The theory of steady-state flux control was applied to characterize the regulation of beta-oxidation flux in uncoupled rat liver mitochondria oxidizing palmitoylcarnitine in the presence of rotenone, malonate and the beta-hydroxybutyrate/acetoacetate redox buffer. By titrations with inhibitors such as antimycin, myxothiazol, azide and 4-pentenoic acid, the flux control coefficients of the b-c1 complex, cytochrome c oxidase and thiolase, were determined experimentally. The flux control coefficients of carnitine palmitoyltransferase II, ETF:CoQ oxidoreductase and beta-hydroxybutyrate dehydrogenase were determined from elasticity coefficients obtained by measuring the flux dependencies of acyl-CoA and acetyl-CoA+CoASH concentrations, the electron transfer flavoprotein redox state, the CoQ redox state and the NAD redox state. It was found that at low flux rates the flux control was distributed mainly between acyl-CoA dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase (Ci = 0.89). At maximum flux rates, carnitine palmitoyltransferase II (Ci = 0.35) and thiolase (Ci = 0.13) contribute additionally to the flux control. Thus, the phenomena of regulation of mitochondrial beta-oxidation can be described as multistep control.

The paper is aimed towards the role of the membrane ecto-enzymes aminopeptidase N (CD13, AP-N) and dipeptidyl peptidase IV (CD26, DP IV) in the immune system. Both peptidases have been identified on T lymphocytes, AP-N also on monocytes and non-T cells. Using enzyme inhibitors and antibodies it has been shown by different groups that DP IV plays a key role in T cell activation and growth. Inhibition studies of our laboratory, using bestatin, actinonin and probestin, also demonstrated an essential role of AP-N in regulation of T cell growth. Moreover, the action of cytokines/lymphokines having DP IV susceptible bonds, as IL-1, IL-2 and IL-6, on lymphocyte proliferation, was found to be suppressed by specific inhibitors of DP IV as well as AP-N. These results are in favour of our hypothesis that DP IV and AP-N, possibly both in a concerted action, are involved in cytokine/lymphokine mediated signalling between immune cells.

A series of hydropolyborate salts were observed to possess hypolipidemic activity in rodents. Tetramethylammonium octahydrotriborate, tetramethylammonium hexahydrohexaborate, tetramethylammonium dodecahydrododecaborate and triethyl-ammonium dodecahydrododecaborate proved to be very effective in lowering serum cholesterol and triglyceride levels in CF1 mice, i.p. and Sprague Dawley rats, orally. Tissue lipids were reduced by these agents e.g. liver cholesterol, and triglyceride and small intestine mucosa cholesterol levels. [3H] Cholesterol distribution studies confirm that steroid levels are lower in most major tissues. The rat serum lipoprotein lipid content was altered by drug treatment, with cholesterol and triglyceride being reduced in the VLDL and cholesterol being reduced in the LDL. HDL cholesterol levels were elevated by drug treatment. The fecal lipids were increased with select derivatives. The enzyme activities involved in de novo synthesis of hepatic lipids were affected by the hydropolyborate salts including cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase.