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H Stockhausen

Publications and source records attributed to H Stockhausen.

At least 19 recordsLinked to original sources
PubMed1995

Inhibition by N-acetyl-5-hydroxytryptamine of nitric oxide synthase expression in cultured cells and in the anaesthetized rat.

1. Induction of the calcium-independent isoform of nitric oxide (NO) synthase (iNOS) in various cell types has been implicated in the circulatory failure in experimental models of septic shock. Tetrahydrobiopterin (BH4) appears to be an essential co-factor for NO formation and therefore an inhibition of its biosynthesis represents a feasible therapeutic target. We have investigated the effects of an inhibitor of BH4 synthesis, N-acetyl-5-hydroxytryptamine (N-acetylserotonin, NAS), on the expression of iNOS in cultured macrophages and smooth muscle cells in vitro, and on the hypotensive response to bacterial lipopolysaccharide (LPS) in the anaesthetized rat in vivo. 2. NAS (0.01-5 mM) caused a concentration-dependent inhibition of the accumulation of nitrite in the conditioned medium of LPS/interferon-gamma (IFN gamma)-stimulated RAW 264.7 macrophages and interleukin-1 beta (IL-1 beta)-activated vascular smooth muscle cells (VSMC). This effect was paralleled by a similar decrease in the iNOS protein content of these cells, as determined by immunoblot analysis. 3. Pretreatment of RAW 264.7 macrophages with the BH4 precursor, dihydrobiopterin (BH2, 0.1 mM) did not restore nitrite formation in the presence of NAS (1 mM). 4. Intravenous administration of NAS (1 mg kg-1 min-1 for 30 min) in anaesthetized rats significantly reduced the fall in mean arterial blood pressure, restored the pressor response to noradrenaline (1 micrograms kg-1), and ameliorated the increase in plasma nitrite following exposure to LPS (10 mg kg-1). 5. NAS pretreatment also attenuated iNOS activity in lung homogenates, as determined by the conversion of radiolabelled L-arginine to L-citrulline, and partially restored the constrictor effect of noradrenaline in aortic rings isolated from LPS-treated rats. Moreover, NAS significantly reduced the rise in the plasma concentration of tumour necrosis factor alpha (TNFalpha) in response to LPS.6. These findings suggest that NAS inhibits the expression rather than the activity of iNOS in cultured macrophages and smooth muscle cells. This effect of NAS appears to be independent of the availability of BH4, but may be related to an attenuation of the release of TNFalpha following LPS administration, as shown in the anaesthetized rat. This mechanism may also account for the beneficial haemodynamic effect of NAS in our experimental model of endotoxaemia.

Anesthesia↗
PubMed1992

Exogenous nitric oxide stress on endothelial cells and macrophages.

Bovine endothelial cells (ECs, P1) and lipopolysaccharide/gamma-interferon-induced mouse macrophages (MMs) were incubated in the presence of SIN-1 and C 3754 (1 microM to 1 mM), sydnonimine metabolites of the antianginal predrugs molsidomine and pirsidomine, respectively up to 48 h. No change of the endogenous nitric oxide output from MMs and A23187- or adenosine triphosphate-stimulated ECs was found by means of the methemoglobin method. Data indicate that downregulation of the nitric oxide (NO) synthase is not obvious within the intact cells under exogenous NO stress supplied by high concentrations of the spontaneous NO donors. Cytosolic MM NO synthase extracts, however, revealed reduction in the enzymic [3H]arginine turnover to [3H]citrulline by SIN-1, but not by C 3786, the pharmacologically active metabolite of pirsidomine.

Amino Acid Oxidoreductases↗
PubMed1986

Naturally occurring conjugated bile acids, measured by high-performance liquid chromatography, in human, dog, and rabbit bile.

The aim of this study was to determine the biliary pattern of conjugated bile acids after stimulation of their enterohepatic circulation. Conjugated bile acids were separated by reversed-phase ion-pair chromatography without prior derivatization. A MicroPak SP-C18-IP-4 column was used as non-polar matrix, and an ionic alkyl compound, tetrabutylammonium phosphate, was added to the mobile phase, which was a mixture of acetonitrile and water. Quantification was made by UV absorption at 210 nm with external standardization. In fourteen human patients with external biliary drainage after papillotomy there was preferential glycine conjugation. The mean values were 36.5% for glycocholic acid, 33% for glycochenodeoxycholic acid, and 10.0% for glycodeoxycholic acid. Only 15.2% of the biliary bile acids were taurine metabolites. Conjugates of ursodeoxycholic acid were below 2.1%. In most cases, conjugated lithocholic acid was not detected. Within 4 h after ingestion of a standardized meal there were no significant changes in the biliary bile acid pattern. In four dogs (beagles), glycine-conjugated bile acids were lacking. The mean values were 74.3% for taurocholic acid, 14.9% for taurodeoxycholic acid, and 5.3% for taurochenodeoxycholic acid. In six rabbits, 87.4% of biliary bile acids was identified as glycodeoxycholic acid and 5.3% as glycocholic acid. In conscious dogs, as well as in rabbits, the stimulation of biliary secretion by cholecystokinin and/or secretin had no effect on the biliary bile acid spectrum. Evidently, there is a difference in the biliary composition of conjugated bile acids between humans, dogs, and rabbits. Because of the different physicochemical behaviour of glycine- and taurine-conjugated bile salts, it seems difficult to compare the therapeutic effect of gallstone dissolution in various species.

Animals↗
PubMed1986

Liver function and pharmacokinetics of molsidomine and its metabolite 3-morpholinosydnonimine in healthy volunteers.

Plasma levels of N-carboxy-3-morpholinosydnonimine ethyl ester (molsidomine, Corvaton) and its pharmacologically active metabolite 3-morpholinosydnonimine (SIN-1) were measured in six healthy male and female volunteers after single intravenous and oral dosing of 4 mg molsidomine. Additionally indocyanine green and phenazone (antipyrine) clearances were determined to estimate hepatic blood flow and metabolic liver function in each subject. The pharmacokinetic parameters of molsidomine were similar to already published data in healthy volunteers and patients. The plasma level of SIN-1 formed was always lower than the molsidomine level but obviously reflects the corresponding molsidomine concentration time course in plasma. Indocyanine green plasma clearance was reduced by 15%. after intravenous dosing of 4 mg molsidomine. There was no clear-cut relationship between the plasma clearances of molsidomine and phenazone in these subjects with normal metabolic liver function.

Adult↗
PubMed1983

Measurement of conjugated bile acids by ion-pair high-performance liquid chromatography.

Vhe quantitatively most important conjugated bile acids in man were separated by reversed-phase ion-pair chromatography without prior derivatization. As non-polar matrix an Ultrasphere I.P. column (C18) was used, and an ionic alkyl compound, tetrabutylammonium phosphate, was added to the mobile phase, which was a mixture of acetonitrile and water. Under these conditions, the glycine and taurine conjugates of cholic acid, chenodeoxycholic acid and deoxycholic acid were separated within 15 min. At 214 nm, the minimum measurable concentration was 1.3-2.0 nmol/ml. The average recovery from bile was 94%. In ten patients with biliary drainage an average of 79.5% of the bile acids were glycine conjugates.

Bile↗
PubMed1983

Radioimmunoassay of bile acids in tissue, bile, and urine.

Two commercially available (Abbott Labs.) radioimmunoassays for determination of conjugated cholic acid and sulfoglycolithocholic acid in serum have been modified for bile acid measurements in alcoholic tissue extracts, bile, and urine. The specificity of both radioimmunoassays has been determined with regard to 27 free and conjugated bile acids. After filtration, bile acids can be measured in urine and bile without prior extraction. Tissue is homogenized and the bile acids are extracted into methanol. Urinary excretion by 64 healthy humans was 2.09 (SD 1.09) mumol of conjugated cholic acid and 8.44 (SD 8.03) mumol of sulfated glycolithocholic acid per 24 h. In liver from 10 patients with various noncholestatic liver disease, the mean concentration of conjugated cholic acid was 32.4 (SD 15.9) nmol/g wet weight. In the liver of 27 male Wistar rats, the concentration of conjugated cholic acid was 41.3 (SD 11.7) nmol/g of tissue, of sulfoglycolithocholic acid 5.1 (SD 2.3) nmol/g of tissue.

Adult↗
PubMed1978

[Mediolateral versus median episiotomy (author's transl)].

From 1969 to 1976, 15,715 episiotomies were done in 24,598 deliveries. The median episiotomy was progressively preferred and the technique of suture improved. The incidence of secondary sutures for dehiscence was reduced from 74 (3.4%) in 1971 to 6 (0.3%) in 1976. Extension into the rectum expectedly rose in incidence. The figures presented, show that the complication rate following mediolateral episiotomy is higher than following median episiotomy including the complication rate with extensions into the rectum.

Episiotomy↗
PubMed1975

[Critical evaluation of paracervical anaesthesia in obstetrics (personal observations in 8038 cases) (author's transl)].

Between 1966 and 1973 a total of 8038 paracervical blockades (PCB) were performed at the Rhine State Women's Hospital in Wuppertal. In recent years the preparation normally used has been Bupivacain (Carbostesin) with adrenalin, 5 ml being injected paracervically. This results in complete analgesia in over 90% of cases. The incidence of forceps deliveries in the PCB group (19%) was higher, while the number of cesarean sections did not increase. Typical PCB-related bradycardias were observed in 6.9% of cases. Taking other forms of bradycardia into account-mainly reduced Dip II-a change in fetal cardiac action was seen in 12% of cases altogether. In 1973 there may have been a causal connection between PCB and postpartum infant death in 2 cases. In cases of acute bradycardia following PCB, intra-uterine reanimation, e.g. with Th 1165 a (Partutisten) under circulation control is recommended. Considering perinatal risks, especially those recognizable cardiotokodynagraphically, paracervical anesthesia is judged to be a suitable method of facilitating birth.

Anesthesia, Obstetrical↗