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Biomedical subjects

H J Mest

Publications and source records attributed to H J Mest.

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

Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits?

The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL.

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

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↗
PubMed1991

Influence of trapidil and derivatives on cholesterol synthesis and esterification in cultured cells.

The effect of trapidil (Rocornal) and its derivatives AR 12456 and AR 12463 on endogenous cholesterol synthesis and on cholesterol esterification rate was studied in human skin fibroblasts (HSF), in human hepatoma cell line Hep G2 and in primary culture of peritoneal macrophages from mouse (PMM). The cholesterol esterification rate was not influenced by the drugs in the tested cell lines. The incorporation of [14C]acetate into cholesterol in HSF was inhibited by AR 12463 and AR 12456, but not by trapidil. The inhibitory potency of AR 12456 in HSF was enhanced after preincubation of the drug with Hep G2 and removal of the medium to HSF, suggesting that the formed metabolite(s) are more potent inhibitors than the parent substance. The metabolite(s) formed seem(s) to influence the first steps in the endogenous formation of cholesterol, because the incorporation of [14C]mevalonate into cholesterol was not significantly inhibited. These findings suggest that the demonstrated inhibition of the endogenous cholesterol synthesis by AR 12456, especially after transformation into a probably more active substance(s), together with the recently described enhanced expression of LDL receptors in Hep G2 cells may partially explain the hypocholesterolaemic activity of AR 12456.

Acetates↗
PubMed1991

[The antiphlogistic effect of the ginkgolide BN 52 021 in the chemically burned rabbit eye].

BN 52 021, a specific antagonist of PAF receptors, was tested in the early-phase treatment of chemically burned eyes in 30 rabbits. The local application of BN 52 021 eyedrops-1% (water-soluble preparation, 5 times daily, in comparison with the other eye as a control) led to a visible anti-inflammatory effect (microscopically and macroscopically) of the chemically burned anterior eye segment. There was only a moderate increase of the concentration of PGF2 alpha after the chemical burn. The use of specific PAF antagonists seems to have a real chance for treatment of inflammatory reactions of the anterior eye segment. A combination with other mediator antagonists should be tested in further experiments.

Animals↗
PubMed1991

Alpha- but not beta-receptor blocking agents inhibit the antiarrhythmic effect of iloprost on ouabain-induced arrhythmia in guinea-pigs.

The effects of iloprost, prazosin and propranolol were tested on ouabain-induced arrhythmia in guinea-pigs. Each drug used alone showed an antiarrhythmic effect. In a second step, iloprost was given in combination with drugs blocking alpha- and beta-adrenergic receptors. Propranolol and iloprost caused a statistically significant and comparable increase of the threshold dose of ouabain for the onset of arrhythmia (OA), the occurrence of premature ventricular beats (PVB), ventricular flutter (VF) and ventricular fibrillation (FIB). The effect of a combination of iloprost and propranolol was comparable to the effect of each drug administered alone. Prazosin enhanced the threshold dose of ouabain for OA and PVB in a statistically significant manner. The effect of a combination of iloprost and prazosin was nearly the same for OA and PVB compared to the single effect of these drugs. The threshold dose of ouabain was decreased for VF and FIB when a combination of iloprost and prazosin was given, compared to iloprost used alone. These results support the assumption that the adrenergic nervous system is involved in the antiarrhythmic effect of iloprost.

Adrenergic alpha-Antagonists↗
PubMed1991

Thromboxane plasma level in kappa-carrageenin-induced acronecrosis of the tail in rats.

The thromboxane A2 (TXA2) plasma level in kappa-carrageenin (KC)-induced acronecrosis in the rat tail has been studied. TXB2 as stable metabolite of TXA2 was determined by a radioimmunoassay (RIA). 30 min after KC i.v. injection, the increase in the plasma TXB2 level was highest in Barby:Wistar rats but not in Halle:Wistar rats. Lambda-carrageenin (LC) increased the TXB2 levels in both strains of Wistar rats, although it did not induce acronecrosis. Drugs inhibiting TXB2 formation, namely dexamethasone, acetylsalicylic acid, Hoe 944, R 68070 or chlorpromazine, had only a small effect on acronecrosis frequency. Heparin inhibited TXB2 formation and acronecrosis frequency while the serotonin antagonist cyproheptadine decreased only the acronecrosis frequency but caused no change in TXB2 plasma level. These data demonstrate that the kappa-carrageenin-induced acronecrosis is followed by an increased formation of TXA2 in rats.

Animals↗
PubMed1991

[Serum thromboxane B2 and prostaglandin F2 alpha in familial combined hyperlipoproteinemia and familial hypercholesterolemia].

In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides.

Adult↗
PubMed1991

Influence of the trapidil derivative AR 12463 on serum and tissue lipids and development of aortic lesions during experimental atherosclerosis in rabbits.

Daily administration of the trapidil derivative AR 12463 (20 mg/kg body weight i.p.) to cholesterol-fed rabbits diminished statistically significantly the increase in serum total cholesterol. After 8 weeks of treatment all measured lipoprotein fractions were significantly lower in animals treated with AR 12463 (group 3) compared with the values of the untreated control (group 1) or vehicle-treated group (group 2). The reduction of serum levels was associated with statistically significantly reduced levels of cholesterol esters in kidney, liver and aorta. The levels of free cholesterol in the liver of group 3 animals were statistically significantly lower compared with the levels in the two other groups, whereas in kidney and aortas the levels of free cholesterol remained unchanged under the influence of AR 12463. The area of aorta covered with fatty streaks was significantly smaller in group 3 versus group 1. The results of this study indicate that treatment of rabbits with AR 12463 while feeding a cholesterol-rich diet prevents hypercholesterolemia as well as the cholesterol incorporation into tissues. The mode of action of AR 12463 on serum and tissue lipids as well as on the development of atherosclerosis is discussed.

Animals↗
PubMed1991

Verapamil and the synthesis of prostacyclin in human veins.

The synthesis of the vasodilator prostacyclin (PGI2) depends on the intracellular calcium concentration. For this reason the purpose of this study was to document the effects of verapamil (1), a slow calcium channel blocking agent on venous tissue. Human varicose veins were studied which were removed by a stripping operation. The veins were investigated ex vivo and in vitro. For ex vivo studies 11 patients were given 0.01 g 1 i.v. during the operation. In vitro experiments were carried out by an addition of 22 mumol/l 1 to the incubate. The synthesis of PGI2 was studied according to the inhibition of the ADP induced platelet aggregation without and with addition of substrate (prostaglandin endoperoxide H2). 1 did not induce changes in the synthesis of PGI2, neither after administration to patients nor after addition to the incubation fluid compared to control vessels without addition of 1.

Adenosine Diphosphate↗
PubMed1990

Effects of platelet activating factor antagonists on arachidonic acid-induced platelet aggregation and TXA2 formation.

The effects of the PAF receptor antagonists WEB 2086, WEB 2170, BN 50739 and BN 52021 on AA-induced platelet aggregation (PA) and TXA2 formation were investigated in comparison with the TXA2 synthetase inhibitor HOE 944 and the TXA2 receptor antagonist BM 13.177. All PAF antagonists tested were weak inhibitors of AA-induced PA and TXA2 formation (IC50 values between 80 and 2,737 mumol/l). HOE 944 was effective in concentrations 2-3 orders of magnitude lower than PAF antagonists in inhibiting TXA2 generation. These results imply that the inhibition of TXA2 formation is of minor relevance for the actions of the investigated PAF antagonists in AA-induced PA.

Animals↗
PubMed1990

Influence of high density lipoprotein (HDL), prepared from human blood, on prostanoid formation, serum and tissue lipids and development of arteriosclerosis in cholesterol rich fed rabbits.

The i.v. administration of high density lipoprotein (HDL) into cholesterol fed rabbits decreased statistically significantly the serum level of total cholesterol and of low density lipoprotein cholesterol after a feeding period of 8 weeks. These diminished levels of cholesterol were associated with a statistically significant reduction in the levels of cholesterol esters in kidneys and platelets but not in hepatic tissue or in aorta. Macroscopically detectable arteriosclerosis was not statistically significantly diminished. The formation of prostanoids by the aorta remained unchanged. The atherogenic role of immunologic factors acting against the heterologous HDL may have compensated for the antiatherogenic HDL action on plasma and tissue lipids.

Animals↗
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

[The improvement of the tolerance of the kidney for ischemia with the prostacyclin analog iloprost].

Operative trauma, ischemia, release of catecholamines and thermal stimuli in consequence of harvesting, preservation and transplantation deteriorate the renal capillary circulation. By crossing of tolerance limits arises an irreversible transplant damage. The conditions of our examinations were placed in this field. By pre- and postischemic application of Iloprost was demonstrable an improvement of the ischemic tolerance of the kidney. Correction of renal hemodynamics, antiplatelet action and cytoprotection are the reasons of the protective influence of Iloprost in our opinion.

Acute Kidney Injury↗
PubMed1990

[Modification of lipoxygenase products in bone by the linoleic acid content of the diet].

Eicosanoids are supposed to participate in the regulation of bone metabolism. 30 male white rats of the wistar strain were fed on a diet rich in linoleic acid (LA), on a diet poor in LA and on a pellet diet after 3 month up to an age of 5 month. The formation of leukotrienes (LT) C4, D4, and E4 from the proximal tibia metaphysis after LA rich diet has been compared to the formation from LA poor and pellet diet. LA rich diet increased the formation of LTC4, D4 and E4 in the proximal tibia metaphysis. The properties of eicosanoids as local mediators in the bone were discussed.

Animals↗
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↗
PubMed1990

[Changes in the spongiosa density in the femoral head of rabbits in atherosclerosis].

Modulations of spongiosa density in the femoral head of rabbits by atherosclerosis. In a long-term study 31 rabbits (+5 control animals) were fed about 20 weeks on a diet rich in cholesterol. An important observation in this study was, that spongiosa density in the femoral head decreases after cholesterol rich diet in contrast to the control group. This effect could be modulated by the Trapidil AR 12463 content (50 mg/die) of the diet, but not by the high density lipoprotein application. Serum cholesterol levels and induced atherosclerosis were determined. Correlations between spongiosa density and atherosclerosis were discussed.

Animals↗