Search PubMed⌕ Search

Biomedical subjects

N Wiernsperger

Publications and source records attributed to N Wiernsperger.

At least 19 recordsLinked to original sources
PubMed1992

The effects of glucose, insulin and metformin on the order parameters of isolated red cell membranes. An electron paramagnetic resonance spectroscopic study.

Human red blood cell (RBC) membranes (RBC ghosts) were treated with glucose, insulin and metformin. The order parameters of RBC membranes were determined by 5- and 16-doxyl-stearic acid spin labels. Metabolic effects were excluded using an isolated system of RBC membranes. The membranes were incubated with glucose in physiological (5 mM), renal threshold (10 mM) and manifested diabetic (20 mM) concentrations for limited times. High concentrations of glucose (10, 20, 100 mM) increase the order parameters of RBC membranes significantly. Insulin by itself has a similar effect which is, however, not strictly concentration-dependent. By contrast, metformin at therapeutic concentrations (0.5 and 5.0 microM) decreases the order parameters. At 50 microM concentration the metformin effect is expressed less and recurs at 100 microM concentration. The effects are significant with 5-doxyl-stearic acid, but are not significant with the 16-doxyl derivative. When RBC membranes are co-incubated with 20 mM glucose and metformin at 0.5 and 5.0 microM concentrations the order parameters as determined by 5-doxyl-stearic acid remain normal (= control values). Higher concentrations of metformin (50 and 100 microM) cause an overshoot to very low order parameters. Insulin at 10, 100 and 200 mU/L does not influence significantly the effects of metformin. Addition of physiological amounts of bovine serum albumin does not abolish the effects of metformin. Metformin, at therapeutic concentrations (0.5 and 5.0 microM), maintains the normal fluidity at the polar interface of isolated RBC membranes by counterbalancing non-enzymatic glycosylation with 20 mM glucose in vitro.

Cyclic N-Oxides↗
PubMed1992

Characterization of metformin transport system in NIH 3T3 cells.

The biochemical properties of the metformin transport system were studied in NIH 3T3 cells. 14C-metformin uptake appeared to be a sodium dependent process. Iso-osmotical replacement of Na+ by choline chloride in the assay medium resulted in a decrease of metformin uptake. Amiloride (200 microM) inhibited the metformin transport by 35% in these cells. Gramicidin, a channel ionophore, was the most effective in inhibiting the metformin transport as compared to valinomycin, a mobile ion carrier, and Ca2+ ionophore (A 23187). Loading of cells with asparagine, ornithine, or polylysine did not influence the uptake process. However, the addition of lysine or arginine significantly stimulated the metformin uptake by NIH 3T3 cells. Similarly, the addition of metformin stimulated the arginine uptake by these cells, suggesting that metformin shares the y+ transport system. Metformin inhibited competitively the uptake of 14C-spermidine, a molecule of the polyamine family, by NIH 3T3 cells, whereas the latter failed to influence the uptake of the former significantly by these cells. Incubation of NIH 3T3 cells in the presence of difluoromethyl-ornithine (a suicidal inhibitor of polyamine biosynthesis) stimulated the spermidine, but not the metformin, uptake by these cells. Interestingly, a prolonged incubation of these cells in the presence of metformin failed to down-regulate the spermidine transport process. The spermidine- and methylglyoxal-bis(guanylhydrazone), MGBG-transport deficient (3T3MG) cells which do not accumulate exogeneous spermidine or MGBG, took up 14C-metformin. However, 14C-metformin uptake by 3T3MG cells was lower than that by normal NIH 3T3 cells.

3T3 Cells↗
PubMed1992

Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment.

This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug.

Animals↗
PubMed1991

Erythrocyte glucose consumption in insulin-dependent diabetes: effect of metformin in vitro.

Erythrocyte glucose consumption in red blood cells from healthy donors or insulin-dependent diabetics with stable glycemia was measured using the 2-deoxyglucose technique. Data showed that the formation of glucose-6P was severely impaired in diabetic red blood cells in both normo- and hyperglycemic incubation conditions. This defect seems to be inherent to the disease. Coincubation with Metformin (6.4 ug/ml) did not modify the G6P levels in RBCs from healthy donors and in RBCs from diabetics when incubated in normoglycemic conditions. However, when diabetics RBCs were incubated in a hyperglycemic medium, addition of Metformin strongly improved the intracellular levels of G6P. The underlying mechanism for the defect and the correction by Metformin remains to be determined. This study shows that also red blood cells may be involved in the failure of glucose homeostasis in diabetes and thus this may represent an additional target for therapy.

Blood Glucose↗
PubMed1990

Serotonin 5-HT2 receptors and brain circulation.

Most evidence in the literature concerning the role of serotonin in ischemia originates from brain research. This is partly because the central nervous system is particularly prone to accumulation of 5-HT, due to the neuronal sources of the amine in addition to circulating 5-HT from platelets. In ischemia, platelet invasion, rupture of the blood-brain barrier, liberation of 5-HT from nerve terminals inside the vessel wall, and necrosis of serotonergic neurons favor local increases of the transmitter in the brain. The pathophysiological consequences include amplifications of processes such as vasoconstriction of major and collateral arteries, edema formation, platelet aggregation, and blood sludging. 5-HT2 receptors appear to be the major effector of these actions of serotonin, judging from experimental and clinical pharmacology data with specific or partial 5-HT2 serotonergic antagonists. This review summarizes current knowledge on the key role serotonin plays in the induction or consequences of brain ischemia.

Animals↗
PubMed1990

The effect of naftidrofuryl on red blood cell aggregation detected in vitro with ultrasound.

Red blood cell aggregates are mainly responsible for the echogenicity of flowing blood. Thus, ultrasound can be used to observe the degree of red blood cell aggregation in slow flow conditions. We quantified blood echogenicity to study aggregation tendency of red blood cells in blood of patients with claudication, patients with suspected venous thrombosis, and normal volunteers without and with in vitro addition of naftidrofuryl (10(-6) M). Normal volunteers showed lower original echogenicity than any group of patients, and claudication patients showed the highest echogenicity. Naftidrofuryl caused a fall in mean echogenicity in all groups, and its effect was pronounced on blood samples with a high original echogenicity.

Aged↗
PubMed1990

Chronic treatment with naftidrofuryl attenuates the development of vascular hypersensitivity to serotonin in the spontaneously hypertensive rat.

Three-month-old spontaneously hypertensive rats were treated for 1, 2, or 3 months with daily intraperitoneal injections of naftidrofuryl (30 mg/kg). Systolic arterial pressure was measured. Tail arteries were removed and perfused at a constant flow rate of 2 ml/min. A concentration-response curve for serotonin was prepared. A second curve was then constructed in the presence of naftidrofuryl. Chronic treatment with naftidrofuryl had no effect on blood pressure but produced a decrease in the maximal vasoconstrictor response and the sensitivity to serotonin in vitro. The in vitro sensitivity to naftidrofuryl was unchanged. These studies suggest that chronic treatment with a dose of naftidrofuryl that does not modify blood pressure attenuates the in vitro vascular sensitivity to serotonin.

Animals↗
PubMed1979

Dopaminergic agonists and their influence on the oxygenation and function activity of underperfused brain tissue.

The effect of two dopaminergic agonists (apomorphine and bromocriptine) on electrical activity and oxygen supply of the brain was investigated in cats submitted to hypovolemic oligemia (mean arterial blood pressure: 45 mmHg). While both drugs stimulated the brain by prolonging the oligemia-induced seizures in the caudate nucleus and in the cerebral cortex, only apomorphine improved the pO2 distribution in the cortical tissue after 120 min oligemia. Bromocriptine, in contrast, had a beneficial effect of shorter duration. These data show that under conditions of incomplete ischemia the brain can still be activated. Furthermore, these results provide additional support for the biochemically founded hypothesis of different dopamine receptors in the brain.

Animals↗
PubMed1978

Effect of carotid ligation on cerebral tissue oxygenation in aging rat.

In order to test the ability of aged animals to compensate a cerebrovascular insufficiency, common carotid ligation was performed on young (12 months) and aged (30 months) rats. By using gold microelectrodes, the pO2 distribution in the cerebral cortex was registered for 1 h following the occlusion of the carotid arteries. It could be shown that, while the young group was able to compensate the reduction in arterial blood supply, the cortical pO2 distribution in the group of aged rats shifted towards a hypoxic profile. These results provide further evidence of the limited adaptability to functional demands with increasing age.

Aging↗
PubMed1978

Cortical pO2 distribution during oligemic hypotension and its pharmacological modifications.

pO2 measurements in the cerebral cortex of cats have shown that the distribution of oxygen within the tissue becomes considerably affected by hypovolemic hypotension, in particular in the late period of oligemia. Pharmacological studies on this model show that the treatment of shock with a vasodilating drug such as papaverine leads to shunt-perfusion, thus impairing the oxygenation of brain tissue. In contrast, administration of the metabolically active drug dihydroergotoxine (DET, Hydergine) results in an improvement of the tissue pO2 distribution in the direction of a pre-shock state.

Animals↗