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Biomedical subjects

C Giessler

Publications and source records attributed to C Giessler.

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

Influence of HDL on the formation of 6-keto-PGF1 alpha and TXB2 in vitro: the importance of the source of HDL.

The influence of HDL, isolated from normolipidemic human blood and blood of normo- and hyperlipidemic rabbits, on in vitro 6-keto-PGF1 alpha synthesis by rabbit aorta and on TXB2 synthesis by platelets of clotting human and rabbit blood was tested. The HDL fraction from normolipidemic subjects, when incubated with blood from normolipidemic humans or rabbits, inhibited TXB2 formation. The same fraction stimulated the formation of 6-keto-PGF1 alpha after incubation with rabbit aorta taken from normolipidemic animals. HDL taken from hyperlipidemic rabbits inhibited 6-keto-PGF1 alpha formation in rabbits and had no influence on TXB2 formation. These results support the hypothesis that not only is the absolute amount of HDL important for its influence on prostanoid formation, but also the origin and the composition of the HDL fraction.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Modulation of TXA2 generation of platelets by human lipoproteins.

The lipoprotein (LP) fractions VLDL, LDL, HDL2 and HDL3 were prepared by ultracentrifugation of plasma from healthy volunteers and from patients with coronary heart disease (CHD). We investigated the capacity of platelets from healthy volunteers and patients with atherosclerosis to generate thromboxane A2 (TXA2) during spontaneous clotting of whole blood under the influence of the lipoprotein fractions. In our experiments the serum concentration of TXB2, reflecting the capacity of platelets to generate TXA2 during clotting, depends on several factors: the type of LP fraction used, the blood used for generation of TXA2, and for the same LP fraction whether it was taken from plasma of healthy volunteers or patients with CHD. VLDL prepared from plasma of healthy volunteers inhibited but VLDL prepared from plasma of patients with CHD enhanced the TXA2 formation of platelets from healthy volunteers (p less than 0.05, resp.). LDL from CHD patients inhibited the TXA2 formation of platelets from atherosclerotic patients (p less than 0.01). The HDL subfractions HDL2 and HDL3 from healthy volunteers inhibited TXA2 formation by platelets from healthy volunteers as well as those from atherosclerotic patients (p less than 0.05; p less than 0.01, respectively). HDL2 from patients with CHD inhibited only the TXA2 formation of platelets from healthy volunteers (p less than 0.01), whereas HDL3 from CHD patients inhibited only the TXA2 formation of platelets from atherosclerotic patients (p less than 0.01).

Adult↗
PubMed1990

[Prostacyclin and thromboxane synthesis in liver tissue in chronic liver diseases].

This paper reports on investigations of the formation of PGI2 and TXA2 using their stabile products 6-keto-PGF1 alpha and TXB2 (RIA) in liver biopsy specimens of 46 patients suffering from fatty liver (n = 19), chronic hepatitis B (n = 11), liver cirrhosis (n = 13), and miscellaneous diseases (n = 3). The measured formation rates in chronic liver disease were evaluated in comparison to a reference group (n = 19) consisting of minimal liver lesions. The 6-keto-PGF1 alpha formation correlating to the degree of the portal inflammation in the liver (morphometric evaluation). The same trend existed in relation to the intralobular inflammation. The results presented suggest in respect of analogous data in animal experiments that PGI2 is predominantly generated in mesenchymal cells of the liver and, presumably influences the course of liver diseases.

6-Ketoprostaglandin F1 alpha↗
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

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↗
PubMed1987

Trapidil derivatives as potential antiatherosclerotic drugs.

Trapidil, a triazolopyrimidine, and its derivatives are coronary vasodilating drugs. Trapidil reduces the serum level of low density lipoprotein- and very low density lipoprotein-cholesterol and increases the serum level of high density lipoprotein-cholesterol in hyperlipemic patients. The present study demonstrates that trapidil and five different trapidil derivatives inhibit the proliferation of cells cultured from grossly normal intima and fatty streaks of human aorta. The inhibiting effect of trapidil derivatives is about 60%, similar to the standard substance 3-isobutyl-1-methyl-xanthine (MIX). In cells cultured from atherosclerotic plaques trapidil and trapidil derivatives reduced the content of cholesteryl esters by 36% for trapidil and between 47% and 68% for 4 of 5 trapidil derivatives, respectively. The trapidil derivative AR 12463 (5-piperidino-7-[N-(n-amyl)-N-(beta-hydroxyethyl)amino]-s-triazolo[1,5- a]pyrimidine) reduces the free cholesterol content by 29%, but the other trapidil derivatives are without effect on this parameter. Four of five derivatives decrease the content of triglycerides by 53 to 70%. The synthesis of collagen is inhibited by the trapidil derivative AR 12463 (25%). Trapidil and other derivatives have a smaller or no effect on the synthesis of collagen. These effects of trapidil derivatives point to potential antiatherosclerotic properties. The possible mechanisms are discussed.

Arteriosclerosis↗
PubMed1987

[The effectiveness of trapidil and some derivatives on heart function under in vitro and in vivo conditions].

Cardiac and coronary effects of trapidil (Rocornal) and some derivatives were investigated in isolated heart preparations and rabbit hearts in vivo. All substances showed a comparable increase of the coronary flow. Contrary to the cardiotonic influence of trapidil the trapidil derivates induced a negative inotropic effect, possibly due to a weak calcium antagonism. Heart rate was slightly diminished, but in some cases higher doses caused an acute tachycardia. I.v. application of the substances to rabbits in doses of 10 mg/kg and 30 mg/kg induced an initial depression of blood pressure normalizing within 3-5 min. An increase of the myocardial prostacyclin biosynthesis is only demonstrable under trapidil. The results indicate that the cardiac effects of trapidil derivatives are possibly caused by a direct influence on the contractile system and the membrane potential of the cardiac muscle cell.

Anesthesia↗
PubMed1987

[Thromboxane A2 antagonistic effect of antiangina drugs, with special reference to trapidil and trapidil derivatives].

In isolated perfused guinea pig hearts and in the cardiocirculatory system of anaesthetized rabbits the thromboxane A2-agonist U 46619 shows cardiodepressive effects. The contraction force of isolated auricle preparations from guinea pigs was enhanced. Antianginous drugs (dipyridamole, propranolol, verapamil, nitroglycerin and trapidil) induced a significant inhibition of the U 46619 effects. Oxyfedrine remained ineffective. The efficiency of some derivatives of trapidil was markedly diminished or abolished in comparison with the original substance. Because of the different chemical structure of the active drugs the TXA2-antagonism is regarded to be caused by a functional influence on the cellular membrane and the calcium transport. Nevertheless the inhibition of the TXA2-effects by antianginous drugs seems to be a factor for the therapeutic use of these substances.

Anesthesia↗
PubMed1986

The influence of lipoproteins (LDL and HDL) on PGI2-formation by isolated aortic preparations of rabbits.

The influence of LDL- and HDL-concentrations of 0.5-2.0 mg/ml and 0.25-1.0 mg/ml respectively, from male and female donors on the formation of PGI2 in isolated aortic preparations was investigated under in vitro conditions. LDL of male donors inhibited endogenous PGI2-formation and the conversion of exogenous PBH2 to PGI2. On the other hand the highest concentration of HDL induced an increase in the basal and in the stimulated PGI2-formation. Lipoproteins of female donors showed no or only a weak stimulating effect on PGI2-formation. Human serum albumin in comparable concentrations of 1-50 mg/ml remained without influence. The importance of the results for cardiovascular diseases is discussed.

Animals↗
PubMed1984

Significance of myocardial prostaglandin biosynthesis and the influence of mechanical loading, endogenous mediators and cardiovascular drugs.

Isolated perfused and electrically driven heart preparations of guinea pigs and tissue from different parts of the rabbit hearts have the capacity to rapidly synthesize prostacyclin (PGI2) and thromboxane (TXB2). Auricles showed a higher PGI2 formation than ventricles. Addition of arachidonic acid or PGH2 markedly enhanced the myocardial PGI2 biosynthesis. After acute pressure overload by a graduated aortic stenosis the PGI2 and TXB2 formation of the myocardium is decreased possibly caused by a diminished availability of substrate, an alteration of enzyme activities or changes in the functional state of the cardiac tissue. Pretreatment with dipyridamole or propranolol again induced an increase of this diminished PGI2 and TXB2 synthesis. The PGI2 formation of electrically driven ventricular strips enhanced with an increased stimulation rate. Ouabain, antianginal drugs (dipyridamole, oxyfedrine, propranolol) and endogenous mediators (norepinephrine, histamine, adenosine) induced a significant rise of the cardiac PGI2 formation. The results suggest that the cardiac prostaglandin biosynthesis is involved in the action of the myocardium indicating heart sufficiency and an adaptability to mechanical loading or drug influence.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Regulatory action of cholesterol esters on the eicosanoid metabolism.

The influence of cholesterol esters (CE) on the formation of prostacyclin (PGI2) and thromboxane A2 (TXA2) depends on the concentration of the added CE and the fatty acid, esterified in the CE. Our results demonstrate that the formation of eicosanoids depends on the CE composition in the microenvironment of the enzymes. Therefore we suggest that the influence of elevated CE levels on the development of atherosclerosis may be also mediated by their influence on the eicosanoid metabolism.

Animals↗
PubMed1984

Drug induced inhibition of the cardiac effects of U 46619 as a thromboxane A2-like agonist.

U 46619 (11,9-epoxymethano-PGH2) appears to be a selective and stable thromboxane-like agonist. In isolated preparations the substance (3.10(-9) - 3.10(-6) mol/l) induced an increase of cardiac performance of auricles and a decrease of contraction force and coronary flow of perfused hearts of guinea pigs. Intravenous infusion of U 46619 (10 micrograms/kg/min) to rabbits caused a marked reduction of heart contractility and blood pressure and the death of the animals within 10 minutes. Antianginal drugs, especially dipyridamole, propranolol, trapidil and verapamil, significantly reduced the TXA2 agonistic effects in auricles and anesthetized rabbits. The results indicate that some antianginal drugs inhibit TXA2 effects in the cardiocirculatory system. This may be regarded as an important factor for the therapeutic use of these substances.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1983

Influence of cardiovascular drugs on platelet aggregation.

All vasodilatory drugs reported in this chapter possess an antiaggregatory effect on platelets, some of them with a synergistic effect on prostacyclin-induced inhibition of aggregation. Thus, the question seems valid whether the antiaggregatory effect represents one part of their antianginal and antihypertensive action. Some vasodilators stimulate the biosynthesis of prostacyclin and/or other vasodilating prostaglandins. This stimulation could be linked not only to the antiaggregatory but also to the vasodilating action. The influence on prostaglandin biosynthesis, however, is not obligatory for all vasodilators, as nitroglycerin proves. Trapidil inhibits the biosynthesis and the effect of thromboxane A2, as our own experiments and those by Ohnishi et al. (7) have shown. This effect could be favorable in patients with heart infarction. Lefer et al. (5) have demonstrated a fivefold increase in thromboxane release after experimental ligation of the coronary artery in the cat. Pinane thromboxane, a thromboxane antagonist, almost completely abolished all deleterious consequences of ischemia. Whether trapidil is also able to inhibit thromboxane biosynthesis and activity under clinical conditions of heart infarction will be the topic of further investigations.

Animals↗