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Biomedical subjects

K Wirth

Publications and source records attributed to K Wirth.

At least 37 records · Page 2Linked to original sources
PubMed1992

Production of cyclic GMP via activation of B1 and B2 kinin receptors in cultured bovine aortic endothelial cells.

The purpose of this study was to define the type of kinin receptors in bovine aortic endothelial cells. As a biochemical response we used the cyclic GMP production which can be attributed to the activation of the soluble guanylyl cyclase of the endothelial cells via endothelium-derived relaxing factor. For the first time we demonstrated that in addition to bradykinin (BK) the B1 kinin receptor agonist desArg9BK increased markedly the content of cyclic GMP. Similar to BK the desArg9BK-stimulated cyclic GMP production was transient and concentration dependent. The effects of both kinin agonists were inhibited by NG-nitro-L-arginine. The known B1 kinin receptor antagonist desArg9[Leu8] BK and the newly discovered antagonist desArg9D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK only inhibited the desArg9BK-stimulated cyclic GMP production. The B2 kinin receptor antagonists D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK and D-Arg[Hyp2,Thi5,8,D-Phe7]BK inhibited the production of cyclic GMP upon stimulation with BK and surprisingly also with desArg9BK. These findings indicate that bovine aortic endothelial cells possess B1 and B2 type kinin receptors which are associated with the production and/or release of endothelium-derived relaxing factor. Furthermore, it was shown for the first time that the B1 kinin receptor in bovine aortic endothelial cells seems to be quite different from that which exists in isolated tissue preparations. The functional importance of these B1 type receptors with regard to regulation of blood pressure and blood flow remains to be determined.

Animals↗
PubMed1991

DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (desArg10-[Hoe140]) is a potent bradykinin B1 receptor antagonist.

DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK is a potent and stable B1 bradykinin (BK) receptor antagonist which was one order of magnitude more potent (IC50 1.2 x 10(-8) M) in the isolated rabbit aorta than the known selective B1 BK receptor antagonist, desArg9-[Leu8]BK (IC50 1.1 x 10(-7) M). DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK is the desArg10 derivative of Hoe140, a new, potent, stable, selective and long-acting B2 BK receptor antagonist. In B2 organ preparation it was three orders of magnitude less potent than Hoe140. Since it is potent and stable it could contribute to the investigation of B1 BK receptor function.

Animals↗
PubMed1991

Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies.

1. Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]bradykinin) is a new bradykinin (BK)-antagonist. It was tested in several in vitro assays and compared with D-Arg-[Hyp2,Thi5,8,D-Phe7]BK. 2. In receptor binding studies in guinea-pig ileum preparations, Hoe 140 showed an IC50 of 1.07 x 10(-9) mol l-1 and a KI value of 7.98 x 10(-10) mol l-1. 3. In isolated organ preparations Hoe 140 and D-Arg-[Hyp2,Thi5,8, D-Phe7]BK inhibited bradykinin-induced contractions concentration dependently, with IC50-values in the guinea-pig ileum preparation of 1.1 x 10(-8) mol l-1 and 3 x 10(-5) mol l-1, respectively. pA2 values in this tissue were 8.42 and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 x 10(-9) mol l-1 for Hoe 140. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK showed an IC50 of 4.0 x 10(-6) mol l-1. The IC50 values in the guinea-pig isolated pulmonary artery were 5.4 x 10(-9) mol l-1 and 6.4 x 10(-6) mol l-1, respectively. In the rabbit aorta no inhibitory effects on Des-Arg9-BK induced contractions were observed. 4. In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10(-8) mol l-1) bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the bradykinin-induced increase in cytosolic free calcium (IC50 = 10(-9) mol l-1). 5. Hoe 140 (10 -7mol I1) totally suppressed the bradykinin-induced (10 8 to 10- mol I') prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta. D-Arg-[Hyp2, Thi5'8, D-Phe7]BK (10- 7 mol I1- ) showed a weaker antagonism. 6. Taken together these results show that Hoe 140 is a highly potent bradykinin antagonist. It was two to three orders of magnitude more potent than D-Arg-[Hyp2, Thi5 8, D-Phe7]BK.

Animals↗
PubMed1991

Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies.

1. The potency, duration of action and tolerability of Hoe 140, a novel and highly potent bradykinin (BK) antagonist in vitro, has been tested in different in vivo models and compared with the well-known BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK. 2. Hoe 140 is highly potent and long acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20 nmol kg-1, inhibition still amounted to 60% whereas the effect of 200 nmol kg-1 of D-Arg-[Hyp2, Thi5,8, D-Phe7]BK was not significant. 3. BK-induced bronchoconstriction in guinea-pigs was strongly inhibited by Hoe 140. The magnitude and duration of inhibition confirmed the findings obtained in the blood pressure experiments in the rat. 4. Carrageenin-induced inflammatory oedema of the rat paw was considerably inhibited at i.v. doses between 0.1 and 1 mg kg-1. 5. In conscious dogs, intravenous doses of 0.01 and 0.1 mg kg-1 of Hoe 140 and D-Arg-[Hyp2, Thi5,8, D-Phe7]BK were well tolerated. At doses of 1 mg kg-1 adverse effects occurred that were attributed to the residual BK agonistic activity of both compounds. 6. Hoe 140 has been shown to be a highly potent and long acting BK antagonist in vivo in different animal species and models. This makes it appropriate to investigate further the physiological and pathophysiological role of BK.

Animals↗
PubMed1988

The adjuvant effect of bacitracin on nasal absorption of gonadorelin and buserelin in rats.

Nasal absorption of gonadorelin (luteinizing hormone-releasing hormone; LH-RH) and buserelin, an LH-RH agonist, was studied in anesthetized rats. Administration of peptides was by nasal instillation of aqueous peptide/buffer solutions. Peptide absorption was monitored using different techniques: (a) by specific radioimmunoassays for serum levels of lutropin (LH), (b) by the cumulative urinary excretion of buserelin, and (c) by the ovulatory activity after nasal LH-RH and buserelin, respectively. Without adjuvant the nasal absorption of LH-RH and buserelin was relatively poor compared to subcutaneous or intravenous injection. Using absorption adjuvants of different types, e.g., sodium taurodihydrofusidate (STDHF) and bacitracin, marked increases in nasal absorption and, therefore, significant nasal adjuvant activity were found, as demonstrated by an increase in the biological response after nasal administration of the peptides. The mucosal compatibility of bacitracin at the concentrations used for enhancement of absorption was confirmed by an in vitro investigation using isolated gastric mucosa of guinea pigs as a test model.

Absorption↗
PubMed1986

Antisecretory effects of two new histamine H2-receptor antagonists.

N-(3-[3-(1-Piperidinylmethyl)phenoxy]propyl)acetoxyaceta mide hydrochloride (Hoe 760) and N-(3-[3-(1-piperidinylmethyl)phenoxy]propyl)glycolamine hydrochloride (Hoe 062) are highly specific H2-receptor antagonists. The compounds are equipotent after intragastrical or intravenous administration. The antagonists inhibited gastric acid secretion in the rat induced by all stimuli tested, carbachol, desglugastrin and histamine. In the Heidenhain pouch dog whose gastric acid secretion was stimulated by food or histamine the two receptor blockers proved to be 4-6 times more potent inhibitors than cimetidine.

Adenylyl Cyclases↗
PubMed1978

[Pharmacokinetic studies on fluoro-alpha-acetyl-digoxin (author's transl)].

Pharmacokinetic studies with a new cardiac glycoside 3H-fluoro-alpha-acetyldigoxin were carried out in humans. The absorption of the drug is 91%. The half-life of tritium label in plasma was 25 h i.v. and 35 h p.o. 73% of the administered radioactivity were excreted after i.v. and 52% after oral administration within 84 h. More than 60% of the radioactivity in the urine could be extracted with chloroform. This fraction corresponded mainly to 3H-fluorodigoxin in the thin-layger chromatogram. Protein binding was 27% using therapeutic concentrations.

Administration, Oral↗
PubMed1977

Immunomorphological lymph node changes in patients with operable bronchogenic squamous cell carcinoma.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T1/2, N0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients, 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitative methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical ("thymus-dependent") area; volume of the follicular (predominantly B-cell) cortex; and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded macrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinuhistiocytosis) correlated inversely with survival. In addition to the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.

Carcinoma, Bronchogenic↗
PubMed1977

[Correlation between immuno-morphological parameters of regional lymph nodes and the mortality of patients with stage I and II bronchial squamos cell carcinoma].

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T 0/2, N 0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitive methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical "thymus dependent") area; volume of the follicular (predominantly B-cell) cortex and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded marcrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinushistiocytosis) correlated inversely with survival. Besides the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.

Carcinoma, Bronchogenic↗
PubMed1976

[Pharmacokinetics of azlocillin, a new semisynthetic, wide-spectrum antibiotic (author's transl)].

Azlocillin, a new semisynthetic penicillin with a wide spectrum of antimicrobial activity and a member of the ureidopenicillin group, was administered to ten adults in a dosage of 2 g by intravenous bolus injection. The determination of antibiotic activity in serum and urine demonstrated an average concentration of 58.9 mug/ml after one hour, 28.1 mug/ml after two hours and 6.1 mug/ml after four hours. The total urinary excretion was 60% within six hours. The pharmacokinetic parameters were calculated for the one and two compartment models, respectively. Mathematical analysis according to an open two-compartment model resulted in better curve adjustment as judged from the sum of the deviant squares. The resulting parameters for volume of distribution and rate of elimination show only minor differences however. Similar results were seen on comparison with the respective data for ampicillin.

Adult↗
PubMed1976

[Kinetics of ampicillin, oxacillin and carbenicillin after a short intravenous infusion in man].

Within 5 min 5 g of ampicillin, oxacillin and carbenicillin, respectively, were administered i.v. to patients with normal kidney function. Plasma levels of the antibiotic activity were measured up to 6 h following the injection. Urine was collected at intervals up to 8 h and the cumulative urinary excretion calculated. Furtheron, biologic half-life, volumes of distribution, total and renal clearance and area under the serum level curve have been assessed for the one- and the two-compartment model. For this model the amounts of drug in central and peripheral compartments were simulated. The statistical evaluation resulted in a highly significantly better fit when the data were analyzed according to the two-compartment model. Despite of these differences the physiological consequences of using the parameters of the one-compartment model were not significantly different.

Adolescent↗
PubMed1975

[Pathophysiologic significance of small intestine flora in the stagnant loop syndrome].

A report is given about a 53 years old man with a "stagnant loop syndrome" associated with a diverticulosis of the whole small intestine and colon. Steatorrhoea was the main clinical symptom. The classification, distribution and frequency of intestinal diverticulosis is based on radiological results. The pathological values of the absorption tests prompted for a discussion of new examinations in the "stagnant loop syndrome". The property of the intestinal bacteria to influence the absorption of fat, xylose and vitamin B12 is stressed. Finally the possible methods of treating the diverticulosis with "stagnant loop syndrome" are discussed.

Bacterial Physiological Phenomena↗
PubMed1975

[Studies on metabolism and pharmacokinetics of alpha-acetyldigitoxin in man (author's transl)].

3H-alpha-Acetyl-digitoxin was administered to 5 patients i.v. and 3 patients p.o. The half-life of label in the plasma was 8.5 +/- 1 (i.v.) and 8.8 +/- 1 (p.o.) days. 20.9 +/- 3.6% (i.v.) and 21.3 +/- 2.9% (p.o.) of the radioactive dose were excreted into the urine in 6 days. Two patients excreted within 18 days 14.3 and 16.1% of the given dose with the stool. After oral administration 22.3% of the orally administered 3H-activity were eliminated into the feces by one patient. 63% (i.v.) and 53% (p.o.) of the chlorofrom-extracted 3H-activity in the urine could be attributed to digitoxin by means of thin-layer chromatography. The volatile content of plasma radioactivity was 4.07 +/- 0.1% (i.v.) and 6.78 +/- 0.2% (p.o.). The protein binding of a 4%. Albumin solution was 83 +/- 0.54%, for plasma 80.8 +/- 2%.

Acetyldigitoxins↗