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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 397 records · Page 22Linked to original sources

Treatment of Parkinson's disease with sodium valproate: clinical, pharmacological, and biochemical observations.

Because there is biochemical evidence of decreased GABAergic function in Parkinson's disease, sodium valproate, an inhibitor of GABA catabolism, was administered to eight Parkinsonian patients. Valproate treatment did not significantly alter any Parkinsonian feature, but tended to increase the dyskinesia in the "on-off" patients. The increased dyskinesias were not a result of altered peripheral metabolism of L-dopa. Despite obtaining high plasma levels of valproate, no consistent alteration of CSF GABA levels could be demonstrated. Thus, in these patients, an effect of valproate on GABA metabolism is unproven, and in turn, the role of GABA in Parkinsonism and dyskinesia uncertain.

Aged↗

Regulation of pancreatic glucagon secretion during a continuous glucose infusion in early and overt diabetics.

The pancreatic glucagon (IRG) secretion pattern was studied during a 2 h glucose infusion test (12 mg/kg/min) in 21 controls as well as in 44 subjects showing different degrees of carbohydrate intolerance. The fasting IRG levels increased significantly from controls (98 +/- 7.6 pg/ml) to chemical (144 +/- 9 pg/ml) and mild maturity-onset-type diabetics (166 +/- 12.2 pg/ml). During artificial hyperglycaemia the glucagon concentrations decreased slightly in all groups, but they remained at a higher level in early and overt diabetics). The molar IRI-IRG ratios have been found to be diminished in patients displaying a disturbed carbohydrate tolerance. There was not any correlation between insulin and glucagon concentrations in the blood. The findings suggest that abnormalities of alpha cell function may be present in early and overt diabetes independent of beta cell responsiveness. The causal relationship of A and B cell function in glucose intolerant subjects has to be cleared in follow-up studies.

Adult↗

Plasma levels of norepinephrine.

Plasma norepinephrine derives from sympathetic nerves, but the proportion reaching the circulation before being metabolized varies with the type of nerve ending-effector junctions in the tissue. Plasma levels of norepinephrine also will fluctuate because of rapid metabolism rates and environmental, emotional, and endogenous stimuli provoking a sympathetic response. The responses of plasma catecholamines in spontaneously hypertensive rats and in normotensive rats of the same strain were compared after exposure to a variety of stressors. Drugs that inhibit monoamine oxidase, catechol-O-methyl transferase, or neuronal uptake were administered to show the effects of metabolic enzymes and neuronal uptake on the amounts of catecholamines reaching the circulation. Sympathetic nervous activity and the ability of the sympathetic nervous system to respond to a uniform stimulus are studied in hypertensive and normotensive subjects. A survey of the plasma levels of norepinephrine in a variety of neurologic disorders is given.

Adult↗

[The immunhistochemical investigation of trypsin and trypsin-like-activity in the small intestine, pancreas and isolated Langerhans islets. A light-, fluorescent- and electron microscopic study (author's transl)].

By means of the indirect immunofluorescence and immunenzyme technique trypsin and trypsin-like activity in fixed cryostate sections of pancreas and gut and pellets of isolated pancreatic islets respectively were investigated using specific antiserum against trypsin. The enzyme was demonstrated in the cytoplasma of the acinus cells, the epithel cell of the intercalated ducts and the excretory (interlobular) ducts of the exocrine pancreas. By light and fluorescence microscopy we could also localize a high activity in pancreatic islets. Results taken from electron microscope show the enzyme in the region of the peripheral endoplasmatic reticulum, the surface of the mitochondria, the zymogen granules of the acinus cells and in the region of the membranes of the endoplasmatic reticulum and in the granules of the B-cells of the pancreatic islets. These results are discussed in correlation with biochemical data concerning the importance of trypsin/trypsin-like activity in the specific conversion of prohormones into hormones.

Animals↗

Influence of pilocarpine pretreatment on (pro)insulin biosynthesis of isolated islets of rats.

3[H]-Leucine incorporation into (pro)insulin and insulin secretion was investigated using islets prepared by collagenase digestion from pancreata of rats pretreated with the cholimimetic agent pilocarpine or with saline (controls). Under the influence of pilocarpine pretreatment the [3H]-leucine incorporation into islet proteins with insulin immunoreactivity is enhanced at 6 mM glucose in the incubation medium of the islets but the incorporated radioactivity at 18 mM glucose is independent of the pretreatment of the animals. Only small or no changes were found regarding insulin secretion. It is concluded that an influence of pilocarpine pretreatment should be taken into consideration using such islets for studies on the regulation of (pro)insulin biosynthesis.

Animals↗

Biosynthesis of somatostatin in pancreatic islets of Wistar rats.

Pancreatic islets of Wistar rats were isolated by collagenase digestion and incubated with [3H]-L-phenylalanine. Using a specific somatostatin antiserum radioactivity was found in the antibody-antigen-complex. The radioactivity was displaced by unlabelled somatostatin. These findings give the first evidence for the biosynthesis of somatostatin or somatostatin-like peptides in mammalian pancreatic islets.

Animals↗

Preparation and characterization of insulin of carp (Cyprinus carpio).

Insulin of carp (Cyprinus carpio) was isolated and crystallized. The insulin was biologically active in two tests; it decreased the blood glucose level and stimulated 14CO2-formation from glucose. The chemical properties are similar to those of insulins from other species. The insulins of carp and of mammals differ greatly immunologically. Antibodies against carp insulin crossreact with carp proinsulin.

Amino Acids↗

[Insulin binding to isolated cells].

Using mono-125I-insulin the hormone receptor binding on cultivated rat hepatocytes cultivated rat fibroblasts and freshly isolated adipocytes of wistar rat and man were characterized. No specific insulin binding was obtained in the case of long time cultivated hepatocytes. The fibroblasts show a low specific insulin binding with an affinity constant of K = 0.75. 10(9)M-1 and a binding capacity of q = 4000 binding sites per cell, and also an insulin response measureable by the lactate production. In agreement with a strong stimulation effect of insulin on the conversion of glucose to CO2 und triglycerides the freshly isolated adipocytes bind insulin with high affinity and capacity in comparison with the fibroblasts. For the high affinity population of insulin receptors at the adipocytes of wistar rat we found K = 2.8 . 10(9) M-1 and q = 22000 binding sites per cell, whereas 20 per cent of saturation of the receptors cause 90 per cent of the maximal stimulation effect on the bio-conversion of glucose. This shift of the binding curve to higher concentrations may be important for the ability of insulin to regulate the carbohydrate metabolism.

Adipose Tissue↗

Plasma concentrations of insulin and free fatty acids in dietary-induced obesity of Wistar-rats before and after glucose stimulation.

Colony-bred Wistar-rats develop obesity after long term feeding with a high-fat diet (50% fat, w/w). According to previous investigations a disturbed glucose tolerance after i.v. glucose load could be described for obese rats. Therefore, we measured peripheral IRI-concentrations before and after glucose stimulation in controls and fat-fed rats. In obese animals we observed a basal hyperinsulinemia in the dynamic phase of development of obesity. In controls and fatty rats, no differences in the peripheral insulin response to an i.v. glucose stimulation could be demonstrated, nor did we find indications of an impaired early insulin response in fatty rats. In accordance with the glucose tolerance study, obese rats in the dynamic phase showed lower FFA-levels (fasting state) and a slower decrease of FFA-concentrations after the glucose-induced insulin enhancement. Changing the feeding schedule at 20 weeks of age, e.g. feeding control diets to fatty rats for 4 weeks, reduced basal IRI-concentrations in these animals to control values. Assuming the secondary nature of the basal hyperinsulinemia in obese rats, our present results demonstrate that the observed impairment of glucose tolerance may be related to the peripheral insulin resistance of skeletal muscle and/or hypertrophied adipose tissue.

Animals↗

[beta2-Microglobulin determination's estimation in cerebrospinal fluid (author's transl)].

beta2-Microglobulin levels were determined the serum and CSF by radioimmunoassay in various patients from departments of neurology and neurosurgery. Simultaneously a study of CSF protein levels was done. In normal subjects, there is a good correlation between blood and beta2m levels. In patients with pure subarachnoid hemorrhage, the beta2m was always found elevated in the CSF. In tumors of the nervous system, the number of cases studied is yet too small to allow any conclusion.

Beta-Globulins↗

Investigations on isolated islets of langerhans in vitro. 16.Modification of the glucose-dependent inhibition of glucagon secretion.

Investigation of glucagon secretion in isolated Wistar rat islets was carried out to elucidate further the regulatory function of glucose and arginine on pancreatic A-cells. The suppressive effect of D-glucose could also be demonstrated with L-glucose, D-mannose, D-fructose, D-galactose, D-glyceraldehyde and DL-dihydroxyacetone, but not in the presence of 3-O-methylglucose or mannitol. Sugars other than D-glucose inhibited glucagon secretion only at much higher concentrations than those at which D-glucose was effective. Furthermore, although 7.5 mM D-glucose up to 80% inhibition, the effects of other sugars appeared to level off at only 50--60% inhibition. The inhibitory action of D-glucose or D-glyceraldedyde on glucagon secretion could not be overcome by L-arginine, but 3-O-methylglucose, mannoheptulose, 2-deoxy-D-glucose, iodoacetamide, theophylline, epinephrine and acetylcholine were effective. The insulin secretion in response to glucose was inhibited by the metabolic inhibitors used, whereas the B-cell response in the presence of glyceraldehyde was diminished by iodoacetamide only. Like D-glucose, a variety of other sugars markedly reduced the stimulatory effect of L-arginine in glucagon release. The results show that the suppression of glucagon secretion is not specific for D-glucose and not strongly connected on a stimulated insulin secretion.

Acetylcholine↗

Plasma noradrenalin and dopamine-beta-hydroxylase during behavioral testine of sexually deviant XYY and XXY males.

In a behavior study of a sexually deviant XYY and XXY male, who were both murderers, plasma noradrenaline (NAA), dopamine-beta-hydroxylase (DBH) were determined radioenzymatically under resting conditions and during exertional and emotional stress. Under a physical sork load on the bicycle ergometer both had normal plasma NA and DBH levels. During emotional stress both had NA increases of the same magnitude. During an arithmetic test NA values did not increase more than expected for the sitting position.

Adult↗