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Biomedical subjects

P Günzel

Publications and source records attributed to P Günzel.

At least 37 records · Page 2Linked to original sources
PubMed1981

Characterization of a new potent heparin. 7th communication: A comparative study of a new potent heparin in human after i.v. application.

The anticoagulant effect of a new potent heparin was compared with commercial heparin after a single i.v. application in human subjects. Determinations of thrombin time, whole-blood clotting time, activated partial thromboplastin time and plasma heparin levels using factor Xa inactivation assay were performed 5, 10, 15, 30 and 60 min after application. The new potent heparin was 1.5 to 2.0 times more effective than commercial heparin per mg dry weight depending upon the coagulation tests used and the length of observation period. In addition, determinations of biochemical and haematological parameters, 24 h after heparin application indicated no signs of any adverse effect.

Adult↗
PubMed1981

Corticosteroid-like effects after high doses of compound (5-methoxy-2-thienyl)-thioacetic acid sodium salt in rats.

During a systemic tolerance study in rats with compound (5-methoxy-2-thienyl)-thioacetic acid sodium salt (MTTA), which is known to decrease the lipolytic process and platelet aggregation, effects after high doses were observed which are similar to the well-known findings after corticosteroid administration. The oral application of MTTA in a dose range from 10 to 1000 mg/kg over a period of 4 weeks resulted in a decrease in total lipids and free fatty acids from 100 mg/kg onwards and an increase in total glycerin and triglycerides after 1000 mg/kg, supplemented with an increased excretion of keto-bodies in urine at all dose levels. The hematological examinations revealed a reduction of blood eosinophils and lymphocytes in males at doses from 10 mg/kg, whereas the eosinophilic granulocytopoiesis was decreased only at the 1000 mg/kg level in both sexes. Determinations of organ weights showed a decrease in thymus weight from 300 mg/kg onwards with an involution at the highest dose levels, being confirmed by histological examination, whereas the adrenal glands' weights were decreased only at the dose level of 1000 mg/kg. Since the endogenous corticosterone level remained unaltered at all doses, it is suggested that these corticosteroid-like effects are directly attributable to MTTA.

Animals↗
PubMed1980

Characterization of a new potent heparin. 1 communication: Determinations of anticoagulant activity of a high potency heparin preparation in vivo using dog as an experimental animal and in vitro using dog and human plasma.

The anticoagulant effect of a highly potent heparin preparation was compared with a commercially available heparin in vivo after i.v. application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time 5, 10 and 30 min after application. The relative potency of the heparin preparation (Schering) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg). The anticoagulant properties of both preparations were also studied in vitro using heparin concentrations from 0.44 to 7.0 microgram/ml dog and human plasma. The relative potency in vitro experiments using dog or human plasma were 1.62 and 1.63, respectively, on the basis of activated partial thromboplastin time. It was further demonstrated that the anticoagulant effect as determined by activated partial thromboplastin time in vitro on human plasma was 2 to 2.4 times more pronounced in both heparin preparations when compared to the effect exerted on dog plasma.

Animals↗
PubMed1980

Characterization of a new potent heparin. 2nd communication: Chemical analysis of the carbohydrate content and determination of the biological activity of a new potent heparin preparation in vitro, using protamine neutralization and amidolytic methods for factor Xa and thrombin.

A new potent heparin preparation was further characterized for carbohydrate content and for biological activities in vitro using the protamine neutralization test and amidolytic methods for factor Xa and thrombin. The chemical analysis of the heparin preparations showed similar amounts of glucosamine and glucuronic acid as known for other heparin preparations. In protamine neutralization test the new heparin was 1.32 times more active than commercial heparin. The amidolytic method using chromogenic substrates S-2222 for factor Xa and S-2238 for thrombin demonstrated that the new heparin was also at least two times more effective than commercial heparin in increasing the rate of inactivation of these serin proteases through antithrombin III.

Animals↗
PubMed1980

Characterization of a new potent heparin. 5th Communication: Further characterization by affinity chromatography on antithrombin-sepharose and its comparison with a commercially available heparin.

A highly potent heparin (Heparin Schering) was characterized in comparison to commercial heparin by affinity chromatography on antithrombin-III-sepharose. Heparin Schering consists of 83% high affinity and 17% low affinity fractions, whereas commercial heparin contained only 40% high affinity heparin and 60% low affinity heparin. The specific biological activities per microgram uronic acid and elution pattern on antithrombin-sepharose of high affinity heparin fraction were similar for both heparin preparations. It is concluded that the 2 times more potent anticoagulant activity of heparin Schering is mainly due to the enrichment of high affinity fraction (83%), which is also present in commercial heparin but at a remarkably lower percentage (40%).

Anticoagulants↗
PubMed1980

Characterization of a new potent heparin. 3rd Communication: Determinations of anticoagulant activity of a new potent heparin preparation by thrombelastography in vitro using citrated dog and human blood.

The anticoagulant effect of a new potent heparin preparation was compared with a commercially available heparin by thrombelastography in vitro using citrated dog and human blood. The relative potency of the new heparin was found to be 1.45 to 1.77 with dog citrated blood and 1.77 to 2.41 with human citrated blood on the basis of different thrombelastographic parameters.

Animals↗
PubMed1980

Characterization of a new potent heparin. 4th communication: The effect of a new potent heparin preparation on lipid components and leucocytes in rats after subcutaneous application.

The effect of a new potent heparin preparation on blood lipid components and leucocytes after a single subcutaneous application in rats was investigated and compared with a commercially available heparin. The analysis of plasma cholesterol, glycerol, triglycerides and free fatty acids as well as leucocyte counts and differential counts were performed 1, 2, 4 and 8 h after heparin application. The main effects observed were a marked increase in free fatty acids with a maximum already after 1 h and a state of leucocytosis with a maximum and 4 h after application, besides other minor changes in blood lipid components. However, these effects were less pronounced after a dose of the new heparin of 16.6 mg/kg, which is equipotent with 5000 USP units of the commercially available heparin used in this study on anticoagulant activity on the basis of factor Xa inactivation assay. The biological relevance of the increase in the plasma free fatty acids and the mechanism of heparin induced leucocytosis are discussed.

Animals↗
PubMed1979

Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man.

Specific neuroendocrine regulatory mechanisms in rats and mice are known to be involved in the development of pituitary tumours (prolactinomas) in systemic tolerance and carcinogenicity studies of oestrogens, certain progestagens and their combinations. However, the susceptibility of the strain used seems to be of decisive importance. High doses of oestrogens may also, in special cases, stimulate development of PRL cell hyperplasia and tumours in humans. In other species such as the hamster long-term treatment with oestrogens results in hyperplastic and neoplastic changes in MSH-producing cells of the pars intermedia of the pituitary gland. On the other hand, in the dog and monkey, steroid-related pituitary tumours were not observed, in spite of long-term treatment with high doses of oestrogens, progestagens and their combinations. The capability of certain progestagens to stimulate canine GH secretion seems to play a major role as mediator of the species-specific progestagen-induced changes (mammary tumours, diabetes- and acromegalic-like syndrome) in the beagle dog. These progestagens also seem to have, in addition to their antigonadotrophic properties, an inhibitory effect on CRH-ACTH and TRH-TSH activity in the beagle bitch. These effects can be demonstrated in both the hypothalamic-pituitary system and in the corresponding peripheral target organs. These findings in the dog were not comparable to the situation in other species including man. The extent to which all these results in different species are applicable to other species depends on whether their neuroendocrine control systems are qualitatively and/or quantitatively similar. The physiological significance of the different pituitary hormones, sensitivity of target organs as well as a certain genetic disposition in the different species should also be considered. All these factors can vary from species to species. From these facts, it can be easily appreciated that results of experiments on different species with a substance possessing the same quality of biological effect in these species (e.g., oestrogen, progestagen, etc.) can only be compared when the experimental procedure takes account of the effect of this substance on the neuroendocrine system of the different species, and when dosage, mode of administration and period of treatment are correspondingly matched to the physiological conditions of each species.

Animals↗
PubMed1979

Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.

The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.

Administration, Oral↗
PubMed1978

Effect of fluocortin butylester and beclomethasone dipropionate on the adrenal gland in beagle dogs.

The effect of butyl-6 alpha-fluoro-11 beta-hydroxy-16 alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) administered intratracheally and of beclomethasone dipropionate given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test including eosinophil counts 5 h after a single i.v. injection of 0.02mg (approximately 2 IU) ACTH/kg body weight were found as well as the histological and morphometrical examination of the adrenal cortex. The cortisol determination (with Clark's method) 1.5 h and eosinophil counts to be the optimum indices for the evaluation of adrenal function. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05; 0.1 and 0.5 mg/kg body weight lead to a dose dependent adrenal suppression on the basis of plasma cortisol concentration, eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg bw. Also the oral administration of 0.1 mg/kg bw./day of beclomethasone dipropionate had a definite adrenal suppressive effect comparable to that of 0.1 mg/kg bw. given intratracheally. However, intratracheal administration of fluocortin butylester even after a 320 times higher dose (2 X 8 mg/kg bw./day) had no suppressive effect on the adrenal gland of the beagle dog.

Adrenal Glands↗
PubMed1977

Effect of cyproterone acetate on prolactin secretion in the female Rhesus monkey.

Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40 mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.

Animals↗
PubMed1977

Isolation and identification of 15-beta-hydroxy cyproterone acetate as a new metabolite of cyproterone acetate in dog, monkey and man.

15-beta-hydroxy cyproterone acetate could be identified by thin layer chromatography, mass spectrum, NMR and IR spectrum as a major unconjugated metabolite of cyproterone acetate in plasma and urine of dog, monkey and man. This metabolite has been found to interferein the Mattingly method for the determination of 11-hydroxy-corticosteroids which suggests, that this method is inadequate in controling the adrenal function of subjects treated with cyproterone acetate.

Animals↗