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H J Mest

Publications and source records attributed to H J Mest.

At least 55 records · Page 3Linked to original sources
PubMed1989

Arachidonate metabolites change furosemide-induced cochlear potentials.

Furosemide-induced changes of cochlear potentials were used as a model to study the influence of arachidonic acid metabolites on ion movements within the cochlea. No influence was exerted by the drugs Esculetin - blocking the synthesis of lipoxygenase products - and Dazoxiben - suppressing thromboxane A2 levels within the cochlea. A weakening of the furosemide-induced changes of the endocochlear potential was found when infusing the thromboxane (TX) receptor antagonists BM 13,505 and BM 13,177 before furosemide was given. This effect was also observed when pre-treating the guinea pig with a specific platelet-activating factor receptor antagonist, BN 52,021, before the diuretics was given. Summating potential and cochlear microphonics remained insignificantly changed against controls. The results suggest that a TX receptor contributes to the control of ion movements within the cochlea. A possible involvement of loop diuretics' receptors is discussed.

Acoustic Stimulation↗
PubMed1989

The effect of PAF in the cochlea of guinea pigs.

The influence of 10(-10) and 10(-9) M PAF/animal given into the jugular vein over 30 sec on inner ear potentials, i.e. endolymphatic potential (EP), summating potential (SP) and cochlear microphonics (CM) was investigated. The EP showed the most pronounced changes. When infusing a specific PAF receptor antagonist, ginkgolide B, or the TXA2 receptor antagonist, sulotraban, before the the infusion of PAF, the changes in cochlear potentials could be completely prevented. A second TXA2 receptor antagonist, daltroban, did not effectively prevent PAF actions. It is hypothesized that these PAF effects are due to an interference with ion transport in the non-sensory structures of the inner ear.

Acoustic Stimulation↗
PubMed1989

The time-course of furosemide-induced strial changes in guinea pigs after pretreatment with daltroban.

It was shown previously (Ernst et al., 1989) that pretreatment of guinea pigs with a thromboxane (TX) receptor antagonist attenuates the decline of the endocochlear potential (EP) induced by furosemide. The present paper is aimed at investigating a possible correlation between the electrophysiological data and ultrastructural changes of the stria vascularis by electron microscopy. The dosages of 40, 60, and 80 mg/kg furosemide were injected after the pretreatment with the TX receptor antagonist daltroban and compared to controls which were injected with furosemide only. It was found at all furosemide concentrations that the strial changes 10 min after injection were nearly unchanged against controls. 30 min after furosemide injection, the most pronounced changes were seen when pretreating the animals: a clear reduction of the marginal cell swelling and edema in general were observed at 40 and 60 mg/kg furosemide. The guinea pigs injected with 80 mg/kg furosemide after pretreatment displayed nearly the same changes as controls.

Animals↗
PubMed1989

Influence of a plasma fraction of human blood, rich in high density lipoprotein, on in vitro formation of prostaglandin I2 (PGI2) and thromboxane A2 (TXA2).

The influence of a plasma fraction of human blood, rich in high density lipoprotein (HDL), was investigated on the "in vitro" formation of PGI2 and TXA2. The addition of 1 mg HDL-cholesterol per ml incubation fluid stimulated significantly the biotransformation of prostaglandin H2 into PGI2 by the microsomal fraction of pig aorta. The TXB2 formation capacity of whole clotted blood was inhibited by administration of HDL in a dose dependent manner. These results suggest that added HDL is able to enhance the ratio PGI2:TXA2. This did not depend on the preparation of HDL either by ultracentrifugation or by precipitation.

Animals↗
PubMed1989

Influence of iloprost on eicosanoid generation and lipid levels in experimental myocardial ischemia in dogs.

Anaesthetized mongrel dogs were subjected to occlusion of a coronary artery. The resulting myocardial infarction was observed for three hours. One hour after occlusion, infusion of the stable prostacyclin analogue iloprost or saline was started. In the control group myocardial infarction was associated with an increase of the ratio TXB2/6-keto-PGF1a which was abolished by iloprost treatment. After occlusion in the control group, the atherosclerosis index (TC-HDLC): HDLC was increased, but in the iloprost-treated group it was significantly decreased. The results of this study suggest that the administration of iloprost is able to prevent changes in eicosanoid metabolism and lipoprotein pattern after coronary artery occlusion in dogs.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Bioavailability of trapidil tablets.

Trapidil was given orally (200 mg, Rocornal dragees 100 mg) and intravenously (100 mg) to 12 healthy volunteers. Serum samples were analyzed for trapidil by HPLC. Complete bioavailability was obtained and a mean absorption time of 66.4 min was calculated using the method of curve moments.

Administration, Oral↗
PubMed1989

[Prostaglandins--local regulators in bone?].

Since the initial discovery by Bergström, prostaglandin E has been the focus of an intense research effort in vitro and in vivo. The regulation of bone resorption and formation involves local as well as systemic factors. In the last decade, prostaglandins have been found to be intimately associated with bone metabolism. One hypothesis consistent that osteoblastic c AMP levels play a central role in determining whether osteoblasts stimulate or inhibit osteoclastic bone resorption. The osteoinductive properties of prostaglandins were discussed.

Animals↗
PubMed1989

[The significance of Ilmaplant as a bone substitute with reference to prostaglandin biosynthesis in bones. An animal experiment-clinical study].

The paper pointed out the resorbable material Ilmaplant-R and the glass ceramic Ilmaplant-L which are used for bone substitution. X-ray, histomorphometric and total mineral contents study were carried out in the region of healing defects in the tibia of 60 male white wistar rats. The healing response of the two bioceramics was compared 12 weeks after implantation. The inductive properties of prostaglandins were discussed. The possibilities of clinical application of Ilmaplant-R were demonstrated on the basis of short-term results up to 12 months.

Animals↗
PubMed1988

Dazoxiben-induced changes in the thromboxane/prostacyclin balance in the lateral cochlear wall of the guinea pig.

Dazoxiben, a thromboxane synthetase inhibitor, was infused i.v. in a first group of guinea pigs. Saline was given to a second group of animals as controls. Subsequently, the lateral cochlear walls of each animal were prepared and analyzed for thromboxane (TXA) and prostacyclin (PGI) using radioimmunoassay. These studies showed that dazoxiben crosses the blood-labyrinth barrier and shifts the TXA2/PGI2 balance in favor of the latter. The effects demonstrated are discussed with respect to the relevance of prostanoids in cochlear physiology.

6-Ketoprostaglandin F1 alpha↗
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

Action of iloprost and PGE1 on global ischemic and reperfused myocardium: a 31P-NMR-study.

The influence of iloprost, PGE1 and of the combined application of iloprost and PGE1 on high energy phosphate contents was investigated in isolated rat hearts perfused aerob at 37 degrees C in Langendorff mode. Changes in creatine phosphate, ATP and inorganic phosphate were registered during 20 minutes of global ischemia and 56 minutes of reperfusion with 31P-NMR-spectroscopic methods starting drug application prior to ischemia simultaneously with onset of heart perfusion. Most effective in preservation of high energy phosphates was the combined application of PGE1 and iloprost resulting in a creatine phosphate/inorganic phosphate ratio of 103.2 +/- 30.9% of pre-ischemia values compared to 52.5 +/- 6.1% in control group without drug application 0-5 minutes after onset of reperfusion, 148.8 +/- 24.8% vs 78.8 +/- 15.2% at 6-11 minutes of reperfusion and 116.6 +/- 16% vs 68.9 +/- 12.7% at 12-17 minutes of reperfusion. The same trend was observed employing ATP/inorganic phosphate ratio. The improved energy state in reperfused hearts following application of PGE1 and iloprost in combination is presumed to be supported by a reduction of the loss of high energy phosphates (HEP) during global ischemia and by a cytoprotective effect of iloprost immediately after starting reperfusion.

Alprostadil↗
PubMed1988

Influence of drugs on the TXA2/PGI2 balance and on the atherogenic index in myocardial ischemia in dogs.

The effect of drugs on eicosanoid production and on the development of atherogenic index was investigated in canine myocardial ischemia. Iloprost, verapamil, the trapidil derivative AR 12463 or 0.9% NaCl solution were administered 60 min after coronary artery ligation in anaesthetized dogs. Both iloprost and AR 12463 reduced the thromboxane A2/prostacyclin (TXA2/PGI2) ratio in coronary sinus plasma in comparison to controls. The atherogenic index was significantly decreased in the iloprost as well as in the AR 12463-treated group in comparison to the control group. Verapamil had no influence on the investigated parameters.

Animals↗
PubMed1988

The effect of substances influencing the arachidonic acid cascade on experimental cardiac arrhythmias.

Substances shifting the balance between thromboxane (TX) and prostacyclin (PGI2) in favour of PGI2 could be of therapeutic value for arrhythmia treatment. This seems to be independent of the pathogenetic mechanism. The TX receptor antagonist BM 13177, the lipoxygenase inhibitor esculetin were effective in ouabain and aconitine induced arrhythmias while the PGI2 formation stimulating substance nafazatrom was only effective in aconitine induced arrhythmia. BM 13177 and esculetin could also counteract the arrhythmogenic effect of PAF. TX synthetase inhibition by HOE 944 was ineffective or partially effective, resp..

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

Effect of derivatives of trapidil on the expression of LDL receptors.

The influence of trapidil and some of its derivatives (AR 12456, AR 12463, AR 12465) on the LDL receptor mediated uptake and degradation of 125 I-LDL by human skin fibroblasts (HSF) and human hepatic cells (HEP G2) was investigated. AR 12456 enhanced the uptake and degradation of 125 I-LDL in HEP G2, but inhibited this pathway in HSF. When this drug was preincubated with HEP G2 cells, and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. Trapidil, AR 12463 and AR 12465 were inactive under the same experimental conditions. These findings suggest that a metabolite of AR 12456 might be responsible for the enhanced expression of LDL receptors in human cells.

Antihypertensive Agents↗
PubMed1988

Investigations on the mechanism of a diminished inotropic isoprenaline effect in isolated rat hearts after high linoleic acid diet.

Male Wistar rats were fed on a diet rich (13.3 J%) or poor (0.5 J%) in linoleic acid for 10 weeks. The inotropic and chronotropic effects of isoprenaline (100 ng) in isolated perfused hearts were reduced after a linoleic acid rich diet by 36% and 51%, respectively, with an accompanying reduction in isoprenaline-induced increase in the ventricular cAMP content. Moreover, the stimulation of adenylate cyclase in homogenates of ventricular tissue was diminished after linoleic acid rich diet. We postulate that the diminished adrenergic cardiac response after high vs. low linoleic acid diets could be due to alterations in the adenylate cyclase activity and cAMP formation.

Animals↗
PubMed1988

Inhibition of cytosolic Ca++ mobilization in human platelets by the antianginal drug trapidil and its derivative AR 12463.

The antianginal drug trapidil (5-methyl-7-diethylamino-s-triazolo-(1.5-a)pyrimidine) and its derivative AR 12463 (5-piperidino-7-(N-(n-amyl)-N-(beta-hydroxyethyl)-amino)-s-triazolo(1.5- a) pyrimidine) inhibit the thromboxane A2 agonist (U-46619)-induced mobilization of intracellular platelet-free Ca++ as measured with the fluorescent Ca++ indicator Indo-1. This inhibitory effect is independent of extracellular Ca++ concentration, and AR 12463 is about 70-fold more active than trapidil itself.

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