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Biomedical subjects

P Mentz

Publications and source records attributed to P Mentz.

At least 19 recordsLinked to original sources
PubMed2003

[Vasoconstrictive Therapies for Bleeding Esophageal Varices and their Mechanisms of Action].

Variceal bleeding is one of the most dramatic complications in gastroenterology and has a high mortality rate. Early treatment with vasoactive drugs can save lives when skilled endoscopists are not immediately available. Vasoactive drugs like terlipressin, somatostatin or octreotide are not only indicated as first-choice emergency treatment, but they also increase the success rate of endoscopic treatments. Whereas the efficacy and mechanisms of action of terlipressin to arrest haemorrhage and to improve the disturbed cardiovascular situation of cirrhotic patients, including those with hepatorenal syndrome, are well documented, the efficacy and mechanisms of action of somatostatin and octreotide remain unclear and uncertain. On account of its vasoconstrictive effects on the dilated splanchnic blood vessels, terlipressin reduces blood flow into the portal vein and, thus, reduces portal venous pressure and blood flow through porto-systemic shunts. As a consequence, variceal bleeding is arrested, central and arterial hypovolaemia is corrected, and activation of the renin-angiotensin-aldosterone system as well as the sympathetic nervous system is reduced, leading to lower intrahepatic and intrarenal resistance. The result is an improvement of organ perfusion - including perfusion of the kidneys and the liver - as well as an improvement of the hyperdynamic cardiovascular situation and a better survival rate. Whereas terlipressin has been shown to stimulate kidney function and to prolong survival time in patients with bleeding esophageal varices as well as those with hepatorenal syndrome, no such promising effects were observed with somatostatin or octreotide.

Clinical Trials as Topic↗
PubMed1999

Bronchodilation using combined urodilatin - albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial.

Urodilatin, the renal form of natriuretic peptide type A, induces bronchodilation, increasing intracellular cyclic guanosine monophosphate (cGMP), whereas the bronchorelaxant effect by b2-agonists is triggered by cyclic adenosine monophosphate (cAMP). The objective of this investigation is to demonstrate the efficacy of urodilatin in inducing bronchodilation, and to show this activity alone or in combination with albuterol. Therefore, a randomized, double-blind, placebo-controlled, dose-finding study with cross-over design was carried out including 12 stable, mild to severe (step 2 to 4, definition by NIH/NHLBI guideline 1997) asthmatics. 96 treatments were thus performed. The intervention was comprised of an intravenous infusion of urodilatin (0, 10, 30, or 60 ng/kg/min) combined with inhaled albuterol (0 or 200 microg). As primary objective, the increase in forced expiratory volume in one second (FEV subset1) was measured. - The trial shows that urodilatin at all applied doses or 200 microg albuterol significantly increases FEV subset1 (p < 0.05). Combination of urodilatin and albuterol treament significantly improves FEV subset1 (p < 0.05) compared to either monotherapy and results in maximum bronchodilation. - From the results, the following conclusions can be drawn. In stable asthmatics, the combined activation of cGMP- and cAMP-mediated pathways results in a significantly improved, maximal bronchodilation in comparison to either type of monotherapy. This shows that urodilatin combined with albuterol improves lung function and ameliorates the therapy in asthmatics.

Adult↗
PubMed1999

Therapeutic use of the natriuretic peptide ularitide in acute renal failure.

BACKGROUND: Ularitide is a member of the natriuretic peptide family. This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide. Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously. Its main action sites are the glomerulum, inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate, and the tubular system inhibiting Na(+)-reabsorption. In initial uncontrolled clinical trials, this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure. METHODS: We conducted a double-blind, placebo-controlled, multicenter, dose-finding trial recruiting 176 patients randomized into 4 different Ularitide doses groups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5. The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours. FINDINGS: The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)). INTERPRETATION: In summary, the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol. Further prospective clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure.

Acute Kidney Injury↗
PubMed1996

Urodilatin is involved in sodium homeostasis and exerts sodium-state-dependent natriuretic and diuretic effects.

Urodilatin is involved in sodium homeostasis exerts sodium-state-dependent natriuretic and diuretic cts. Eight male volunteers participated in a study consisting of three consecutive phases of 7 days each. The volunteers a sodium diet with 52, 172.6, and 347.8 mmol um/day. Sodium excretion increased from 57.4 +/- 3.7 via .8 +/- 4.6 (P < 0.001) to 322.5 +/- 10.2 mmol/24 h (P < 0.001) at the end of each sodium diet. Urinary urodilatin excretion increased from 24.8 +/- 3.0 via 35.5 +/- 9.0 (P = 0.07) to 49.0 = mol/min (P < 0.01). At the end of each diet, urodilatin was infused for 2 h at 20 ng.kg body wt-1.min-1. Natriuresis increased after low- (4.1 to 52.9 mmol/h, P < 0.001), normal (6.9 to 44.9 mmol/h, P < 0.05), and high-sodium diet (20.1 to 102.9 mmol/h, P < 0.001). Diuresis increased from 174 to 709 (P < 0.001), 395 to 1,026 (P < 0.05), and 266 to 1,339 ml/h < 0.001). The present results indicate that endogenous urodilatin plays an important role in sodium homeostasis and that renal response to exogenous urodilatin is modulated by sodium balance.

Adaptation, Physiological↗
PubMed1995

Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation.

Acute renal failure is a serious problem following heart transplantation. In first uncontrolled clinical trials, Urodilatin revealed beneficial effects in the prophylaxis and therapy of acute renal failure following heart and liver transplantation. Here, we present the first randomized, placebo-controlled, double-blind study on 24 patients following heart transplantation to investigate whether prophylactic i.v. Urodilatin infusion can prevent acute renal failure requiring renal replacement therapy. Postoperative drug management was characterized by intravenous application of high furosemide, cyclosporine, and vancomycin doses. Urodilatin infusion was started postoperatively with a dose of 40 ng / kg bw / min for 6 days. 6 of the 12 patients in the Urodilatin group and 6 of the 12 patients in the placebo group had a stable diuresis (3 - 4 l / day) during the study period of 6 days. In contrast, the remaining 6 patients of each group developed oliguria / anuria and required subsequent hemofiltration / hemodialysis. Cumulative duration of hemofiltration (88 +/- 7.39 hours in the placebo treated patients versus 44 +/- 5.35 hours in the Urodilatin treated patients, p < 0. 05) as well as frequency of hemodialysis (3.0 +/- 0.49 times in the placebo group vs 1.2 +/- 0.29 times in the Urodilatin group, p < 0. 05) were significantly reduced using Urodilatin. Mean arterial blood pressure was stable during the Urodilatin infusion period and was not different to that observed in placebo patients. We conclude that Urodilatin does not reduce the incidence of acute renal failure and the subsequent requirement for hemofiltration / hemodialysis in our patient population, but seems to reduce the duration of hemofiltration and frequency of hemodialysis compared to the placebo group.

Acute Kidney Injury↗
PubMed1992

Biosynthesis of TXB2 and 6-oxo-PGF1 alpha in the heart and other tissues under pathophysiological conditions.

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Influence of a cholesterol rich diet in rabbits on the formation of PGI2 and TXA2.

In the study was investigated whether the formation of prostanoids is changed in the different regions of aorta or in clotting whole blood in dependence on development of atherosclerosis. For this question New Zealand rabbits were fed for different periods with a cholesterol rich diet (0.5%). At the end of the different dietary periods the animals were killed and the following parameters estimated: blood: levels of total cholesterol, HDLcholesterol, VLDLcholesterol, cholesterol in the beta-migrating lipoprotein fraction, serum lipid peroxides, TXB2 formation capacity of clotting whole blood; aorta: surface of intima covered with fatty streaks, free and esterified cholesterol, triglycerides, collagen, formation of 6-keto-PGF1a and TXB2 by abdominal and thoracic aortas. The lipid parameter demonstrated a relatively strong correlation with the duration of cholesterol rich diet or the macroscopically detectable atherosclerosis, but the prostanoid formation remained unchanged.

Animals↗
PubMed1992

Interactions of prostanoids with the platelet activating factors.

The platelet-activating factor (PAF) induced a marked increase of the thromboxane (TX) B2-formation in the incubation medium of isolated myocardium and tissue from other organs. The content of the 6-oxo-prostaglandin (PG)F1 alpha, the inactive metabolite of PGI2, remained uninfluenced or showed a small decrease. PAF, given in a concentration of 2.10(-9) mol/l or a single dose of 100 ng, significantly reduced the contraction force and the coronary flow of isolated guinea-pig hearts. This effect was connected with a high efflux of TXA2. The PAF-antagonist, WEB 2086, nearly abolished the cardiac effects of PAF, and iloprost or a pretreatment with indomethacin markedly reduced the PAF-influence on the heart. The TXA2-antagonist BM 13177 was ineffective. The results indicate a close interaction between the myocardial PAF-effect and the TXA2-formation of the heart tissue, but gave no suggestion for a mediation of the PAF-effect by TXA2. The PAF-antagonistic action of WEB 2086, iloprost and indomethacin could be of some interest in the therapy of cardiovasculatory diseases.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

[The effect of indomethacin and iloprost on the cardiodepressive actions of various anesthetics on isolated atrial preparations from guinea pigs].

Effects of Indomethacin and Iloprost on the Cardiodepressant Properties of Various Narcotics on Isolated Auricle Preparations from Guinea Pigs. In isolated auricle preparations from guinea pigs several narcotics (hexobarbital, pentobarbital, ketamine, etomidate, urethane) dose-dependently showed cardiodepressive effects. Premedication of the preparations with indomethacin significantly reduced the narcotics-induced changes of the cardiac action. Iloprost, a stable prostacyclin analogon, had the same efficacy. The influence of both substances could be due to an unspecific membrane effect or a positive inotropic action.

Anesthetics↗
PubMed1989

[Prostacyclin (PGI2) biosynthetic activity in variously differentiated neoplasms and the surrounding tissue].

For further elucidation of the connection between tumor differentiation, intensity of stroma reaction and the capacity of prostacyclin biosynthesis comparable investigations were performed on the PGI2 formation and the microscopic pattern of 10 tissue samples from naevus cell tumors, skin basalioma, oral pavement epithelium carcinoma and their direct adjoining region. The effects were compared with 10 tissues from healthy oral mucosa and facial skin. The results indicate that the PGI2 activity depends on the quantity of cells within the tissue. The various cells were stimulated in a different manner. The highest values of the PGI2 biosynthesis were found in cells of an inflammatory proliferation direct adjoining the oral pavement epithelium carcinoma. This shows a connection between tumor differentiation, intensity of stroma reaction and the activity of prostacyclin biosynthesis, possibly indicating a criterion of malignity for the prognosis of the tumor disease.

Basal Cell Carcinoma↗
PubMed1989

[Enzyme immunoassay for thromboxane B2].

A sensitive and specific enzyme immunoassay for TXB2, the stable degradation product of thromboxane A2, was developed, in which the hapten molecule was labeled with pure peroxidase. After competitive binding to antibody between enzyme-labeled and free TXB2, the immunoreactive product was precipitated by double antibody technique, and the enzyme activity of the precipitate was determined spectrophotometrically. The procedures allowed a determination of 3-200 pg TXB2/tube (0.081 to 5.4 nmol/l).

Animals↗
PubMed1988

Interaction of iloprost and indomethacin with the cardiac effects of isoprenaline, ouabain and trapidil.

Investigations in isolated heart preparations of guinea pigs showed, that iloprost enhanced the increase of cardiac performance by isoprenaline, but inhibit the positive inotropic effect of ouabain. On the other side pretreatment with indomethacin induced a significant rise of the cardiac effects of both isoprenaline and ouabain. The efficacy of trapidil and oxyfedrine remained uninfluenced. The results indicate, that prostanoids and cyclooxygenase inhibitors influence the effects of the investigated cardiac drugs. This is possibly be due to changes in the cellular membrane and the intracellular calcium content and should be considered in the therapeutic use of these substances.

Animals↗
PubMed1988

Significance of the cardioprotective effect of prostanoids and indomethacin.

Recent investigations in several organs indicate cytoprotective effects of prostanoids. For further elucidation of this efficacy the investigations dealt with the cardioprotection of prostanoids (iloprost, PGE1) and the cyclooxygenase inhibitor indomethacin under in vivo- and in vitro-conditions. The experiments were carried out in isolated perfused guinea pig hearts and anaesthetized rabbits. Cardiac damage was induced by chemical substances or loading by aortic constriction or ischemia. In isolated perfused hearts iloprost and indomethacin suppressed the toxic effects of carbon tetrachloride, chloroform, benzene, sodium dithionate and phenylethylbarbituric acid, but not the efficacy of quinine sulfate and 2,4-dinitro-phenol. Cardiac loading by aortic stenosis or ischemia induced a decrease of contractility and blood pressure and changes in the myocardial PGI2-biosynthesis. On the other side application of indomethacin, iloprost or PGE1 diminished the cardiac damage and inhibit the myocardial PGI2-formation. The results show that indomethacin and prostanoids have a protective effect in pathophysiological changes or toxic damage of the heart, possibly caused by a stabilization of the cellular membrane.

Alprostadil↗
PubMed1988

Myocardial biosynthesis of prostacyclin and the influence of cardiac loading and drugs.

Cardiac tissue from different parts of hearts from guinea pigs and rabbits have the capacity to rapidly synthesize prostacyclin (PGI2). Auricles show a higher PGI2-formation than ventricles. Addition of the endoperoxide PGH2 markedly enhanced the myocardial PGI2-biosynthesis. Furthermore many cardiotonic drugs induced a significant rise, but eicosanoids or cyclooxygenase inhibitors a marked reduction of the cardiac PGI2-formation. Acute pressure overload by graduated aortic stenosis, ischemia by coronary ligation or pacing with high frequency reduced the cardiac contractility. After aortic stenosis the myocardial PGI2-biosynthesis is lowered, but increased after coronary ligation or pacing. Under these conditions indomethacin, PGE1, iloprost, verapamil and trapidil markedly reduced the PGI2-biosynthesis and exert a protective effect in regard to cardiac damage. The results indicate that pathophysiological changes significantly influence the PGI2-biosynthesis of the heart. The drug induced inhibition of the myocardial PGI2-formation parallels a cardioprotective effect of these substances.

Animals↗
PubMed1988

An enzyme-linked immunoassay for thromboxane B2 and 6-oxo-PGF1 alpha using peroxidase as label.

A sensitive and specific enzyme immunoassay was developed for TXB2 and 6-oxo-PGF1 alpha, stable degradation products of TXA2 and prostacyclin. The hapten molecule was labeled with pure peroxidase. After competitive binding to antibody between enzyme-labeled and free prostanoids the immunoreactive complex was precipitated by double antibody technique. The enzyme activity of the precipitate was determined spectrophotometrically. The procedure allowed a determination of TXB2 and 6-oxo-PGF1 alpha in the range of 3-200 pg (0.008-0.53 pmol) and 10-1000 pg (0.028-2.8 pmol) respectively.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effects of beta-casomorphin in isolated heart preparations.

beta-Casomorphin-5, a novel opioid peptide Tyr-Pro-Phe-Pro-Gly, was tested in isolated heart preparations of guinea pigs in comparison with other morphine related peptides and cardioactive drugs. The substance induced a dose-dependent change in the cardiac contraction force, showing a positive inotropic effect in low concentrations (10(-9) - 10(-7) mol/l) but a cardiodepressive action at higher doses (10(-7) - 10(-5) mol/l). Similarly, potentiation phenomena due to varied pacing rates of right-ventricular strips were enhanced at 10(-8) mol/l and lowered at 10(-6) mol/l beta-casomorphin-5. The coronary flow continuously increased. The observed changes of heart action were not mediated by opioid receptors: specifically acting opioid peptides were without influence and naloxone had no inhibitory effect. Peptides with similar sequences may exert a regulatory role in cardiac function, possibly mediated by an influence on the cellular calcium fluxes. The results may prove to be useful for the detection and estimation of more stable and cardioactive peptides.

Animals↗