Biomedical subjects

U Diczfalusy

Publications and source records attributed to U Diczfalusy.

At least 73 records · Page 4Linked to original sources

PubMed1990

Stanozolol and experimental atherosclerosis: atherosclerotic development and blood lipids during anabolic steroid therapy of New Zealand white rabbits.

Exogenous oestrogens have been shown to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and reduce the severity of experimental atherosclerosis. In contrast, exogenous progestogens, testosterone and anabolic steroids have been shown to increase the level of LDL cholesterol and decrease the level of HDL cholesterol in man. We induced atheromatosis through cholesterol feeding of New Zealand White rabbits of 1% cholesterol (w/w) food supplementation for three months. Furthermore, control rabbits and cholesterol rabbits respectively, were given stanozolol 5 mg per day orally for the first 6 weeks and thereafter 10 mg per day. We found no significant influence of the anabolic steroid stanozolol either on the extent of atherosclerotic involvement or on HDL or LDL cholesterol. However, we could not exclude an influence of stanozolol on the development of atherosclerosis because of the finding that two out of 10 stanozolol-treated rabbits on normal diet developed macroscopic atherosclerosis compared to none out of 72 rabbits of the same age from previous studies given the same normal diet (p = 0.013).

Animals↗

PubMed1990

Identification of metabolites from peroxisomal beta-oxidation of prostaglandins.

We have recently shown that isolated rat liver peroxisomes can chain-shorten prostaglandin F2 alpha and prostaglandin E2 to tetranor-metabolites. In the present report dinor-metabolites of these two prostaglandins were also identified, suggesting that the peroxisomal chain-shortening reaction of prostaglandins is a beta-oxidation reaction. Furthermore, an intermediate containing an extra double bond was isolated from incubates of prostaglandin F2 alpha with peroxisomes. This intermediate was tentatively assigned the structure 2,3-dehydroprostaglandin F2 alpha. Prostaglandin E1 and a major circulating prostaglandin F2 alpha metabolite were also metabolized to chain-shortened products by peroxisomes. The accumulation of the 2,3-dehydro-metabolite and the dinor-metabolites suggest that the peroxisomal beta-oxidation sequence is not tightly coupled, in contrast to mitochondrial fatty acid oxidation.

Alprostadil↗

PubMed1989

Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit.

Administration of moderate pharmacological doses of oestrogen to cholesterol-fed rabbits for 12 weeks resulted in a dramatically retarded development of arterial lesions as compared to non-oestrogen-treated, cholesterol-fed rabbits (7% vs. 47% aortal involvement). Oestrogen treatment was associated with a retarded increase in plasma cholesterol, and five times higher high density lipoprotein (HDL) to very low density lipoprotein (VLDL) cholesterol ratio. Expression of hepatic lipoprotein receptor activity, as detected by heparin-releasable binding of 125I-hypercholesterolaemic VLDL, was heavily suppressed by cholesterol feeding. Administration of oestrogen modulated this response and resulted in higher receptor expression. In accordance, oestrogen treatment resulted in a less prominent reduction of 125I-hypercholesterolaemic VLDL clearance in the cholesterol-fed rabbits. VLDL from both groups of cholesterol-fed animals stimulated cholesteryl ester synthesis in cultured macrophages to the same extent. Thus, in rabbits under a dietary cholesterol load, oestrogen counteracted hepatic lipoprotein receptor suppression, reduced plasma VLDL- and increased plasma HDL-cholesterol levels, and to a large extent abolished the development of atherosclerosis.

Animals↗

PubMed1988

Attempts to define the minimal serum level of vitamin A required for normal visual function in a patient with severe fat malabsorption.

A case with severe malabsorption of fat soluble vitamins is described. The malabsorption developed after an intestinal bypass operation due to morbid obesity. Night blindness occurred as the first symptom of vitamin A deficiency. The cone visual sensory threshold was elevated about one log unit and the rod threshold abot two and a half log units. No changes of the a- and b-waves of the electroretinogram (ERG) was observed. However, during the initial phase of very low serum reninol level (0.21 mumol/l) the summed amplitudes of the oscillatory potentials (OPs) were lower. After parenteral therapy with vitamin A the night blindness disappeared and the dark-adapted rod and cone threshold sensitivity recovered to normal. However, the time-course of rod adaptation first reached normal levels after 5 months. The amplitudes of the OPs of the ERG response returned to normal when the serum retinol level had increased close to normal. Serum retinol levels of 0.7 mumol/l or higher were always associated with normal or close to normal dark-adapted rod sensitivity. However, a normal serum retinol level (> 0.95 mumol/l) and a normal dark-adapted rod threshold sensitivity were not always associated with a normal time-course of the rod adaptation. It is concluded, that the maintenance dosage of vitamin A must be individualized and that patients who have undergone jejuno-ilea bypass surgery must be carefully monitored for vitamin A deficiency by both serum levels and dark adaptation measurements.

Dark Adaptation↗

PubMed1988

Peroxisomal chain-shortening of prostaglandin F2 alpha.

We have recently reported that prostaglandin F2 alpha can be chain-shortened by isolated rat liver peroxisomes. In the present study it is further established by cell fractionation experiments that the enzymes involved in this reaction are localized to peroxisomes. Under the conditions employed, the highest activity was found in the light mitochondrial fraction. Further fractionation of the light mitochondrial fraction by sucrose density gradient centrifugation showed that the prostaglandin oxidation activity comigrated with peroxisomal marker enzymes. Di(2-ethylhexyl)phthalate treatment resulted in a tenfold increased capacity for the conversion of prostaglandin F2 alpha into tetranorprostaglandin F1 alpha. The reaction was not inhibited by KCN. The reaction was further characterized with respect to cofactor requirements. The prostaglandin oxidation was found to be completely dependent on NAD, CoA, ATP, Mg2+ and was stimulated by FAD. Incubation of prostaglandin E2 with peroxisomes resulted in conversion into several products. After alkaline hydrolysis, one of these was identified as tetranorprostaglandin B1.

Animals↗

PubMed1987

Chain-shortening of prostaglandin F2 alpha by rat liver peroxisomes.

Liver peroxisomes were isolated from di(2-ethylhexyl)phthalate treated rats by isopycnic sucrose gradient centrifugation of a light mitochondrial fraction. Incubation of prostaglandin F2 alpha with purified peroxisomes resulted in conversion into a more polar product(s). In contrast, incubation with mitochondrial fractions and microsomal fractions under the same conditions did not result in any detectable conversion. The polar material obtained from a preparative incubation was purified by high performance liquid chromatography and characterized by radio-gas chromatography and gas chromatography-mass spectrometry. The structure of the polar compound was shown to be 5,7,11-trihydroxy-tetranorprost-9-enoic acid (tetranor-prostaglandin F1 alpha). Prostaglandin F2 alpha was thus chain-shortened by four carbon atoms.

Animals↗

PubMed1987

Determination of 4-methylpyrazole in plasma using solid phase extraction and HPLC.

A rapid method for the determination of 4-methylpyrazole in plasma is described. Internal standard (3-methylpyrazole) is added to the plasma which is subsequently applied to a BondElut SCX column. After washing the column the 3- and 4-methylpyrazoles are eluted with a phosphate buffer and analyzed by isocratic reversed-phase high performance liquid chromatography with UV detection. The concentration of 4-methylpyrazole is calculated from the 4-methylpyrazole/3-methylpyrazole peak height ratio. The method is linear between 2.5 and 100 mumol/L with a within-day precision (CV) of 2.2% (n = 10) and a day-to-day precision of 2.8% (n = 30). The sensitivity is sufficient for analysis of plasma levels in the low micromolar range.

Chromatography, High Pressure Liquid↗

PubMed1987

Products, kinetics, and substrate specificity of homogeneous thromboxane synthase from human platelets: development of a novel enzyme assay.

Homogeneous thromboxane synthase from human platelets converted prostaglandin H2 (PGH2) to thromboxane A2 (measured as thromboxane B2, TxB2), 12(L)-hydroxy-5,8,10-heptadecatrienoic acid (HHT), and malondialdehyde (MDA) in equimolar amounts under a variety of experimental conditions. PGG2 was transformed to MDA and corresponding 15- and 12-hydroperoxy products. PGH1 was enzymatically transformed into 12(L)-hydroxy-8,10-heptadecadienoic acid (HHD) and PGH3 into TxB3 and 12(L)-hydroxy-5,8,10,14-heptadecatetraenoic acid (delta 14-HHT) as earlier reported for solubilized and partially purified thromboxane synthase preparations. The ratio of thromboxane to C17 hydroxy fatty acid formation was 1:1 with PGG2, PGH2, and PGH3 as substrates. These results confirm and extend earlier observations with partially purified enzyme that the three products are formed in a common enzymatic pathway (Diczfalusy, U., Falardeau, P., and Hammarström, S. (1977) FEBS Lett. 84, 271-274). A convenient spectrophotometric assay for thromboxane synthase activity measuring the ultraviolet light absorption of the C17 hydroxy acid formed (e.g., HHT) was developed. The validity of the assay was determined employing specific inhibitors for thromboxane synthase. The substrate specificity of thromboxane synthase was determined using this assay. PGG2 and PGH3 showed Vmax and KM values similar to those of PGH2. The KM value of PGH1 was also identical to that of PGH2 but the Vmax value PGH1 was more than twice as high as that of PGH2.

Blood Platelets↗

PubMed1987

Increased aortic thromboxane production in experimental atherosclerosis.

It is of great importance to clarify the role of thromboxane and prostacyclin in the process of atherosclerosis. In order to study this we induced atherosclerosis in rabbits through cholesterol feeding (1% w/w) for three to 12 weeks. After sacrifice the aorta was quickly removed and incubated. The in vitro thromboxane production measured as immunoreactive thromboxane B2 increased by 86 per cent in atherosclerotic vessels compared to control vessels (p less than 0.0005). The in vitro production of prostacyclin measured as immunoreactive 6-keto-prostaglandin F1 alpha showed a tendency to higher values in the atherosclerotic vessels compared to the control vessels (31%, p less than 0.025). This suggests that an increased thromboxane production rather than a decreased prostacyclin production might be important for the progression of atherosclerosis.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Identification of the major urinary metabolite of prostaglandin E3 in the rat.

[11,12-3H2]Prostaglandin E3 was administered subcutaneously into male Sprague-Dawley rats in doses of 0.4 microgram-10 mg/kg body weight. 40-60% of the administered radioactivity was excreted in the urine. The major metabolite was isolated by solid phase extraction followed by three steps of high-performance liquid chromatography. The structure of the major metabolite (5-11% of the administered radioactivity) was 7 alpha,11 alpha-dihydroxy-5-ketotetranorprosta-9,13-dienoic acid as shown by gas-liquid chromatography-mass spectrometry and by its conversion into 11 alpha-hydroxy-5-ketotetranorprosta-4(8),9, 13-trienoic acid.

Alprostadil↗

PubMed1985

Formation of 15-HETE as a major hydroxyeicosatetraenoic acid in the atherosclerotic vessel wall.

Atherosclerosis was induced in New Zealand White rabbits through cholesterol feeding. Aortae were taken out from treated animals and incubated with arachidonic acid. Aortae from cholesterol-fed animals converted arachidonic acid into 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). This conversion was not seen in aortae from control animals. The immediate precursor of 15-HETE, 15-HPETE, is an inhibitor of prostacyclin synthetase and might hamper prostacyclin production.

Animals↗

PubMed1985

Influence of dietary partially hydrogenated vegetable and marine oils on membrane composition and function of liver microsomes and platelets in the rat.

The aim of the present study was to investigate the influence of partially hydrogenated vegetable and marine oils on membrane composition and function of liver microsomes and platelets with particular reference to the metabolism of linoleic acid and the production of arachidonic acid metabolites. Four groups of male weanling rats were fed linoleic acid supplemented diets containing 20% (w/w) of partially hydrogenated low erucic acid rapeseed oil (HLRSO), partially hydrogenated herring oil (HHO), olive oil (OO) and trierucin + triolein (TE) for 10 weeks. An additional two groups were fed partially hydrogenated low erucic acid rapeseed oil and partially hydrogenated herring oil without linoleic acid supplementation (HLRSO- and HHO-, respectively). Substantial amounts of trans fatty acids were incorporated into liver microsomes (12.6% in group HLRSO) and platelets (7.0% in group HLRSO-). This incorporation was not dependent on the dietary linoleic acid level. Hepatic microsomal delta5 -desaturase activity was significantly increased after HLRSO feeding compared to 00 feeding. Delta6 -Desaturase activity did not vary in the linoleic acid supplemented groups. Both delta5 -and delta6 -desaturase activities were significantly increased in groups without linoleic acid supplementation. Docosenoic acid was incorporated into platelet phospholipids in contrast to liver microsomes. In the platelet, docosenoic acid seemed to have a special preference for phosphatidylserine. Very small amounts were incorporated into platelet phosphatidylinositol. Feeding diets HLRSO, HHO and 00 did not influence rat platelet cyclooxygenase or 12-lipoxygenase activity. Platelets from rats fed TE, however, produced significantly less 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) than platelets from rats fed OO. Feeding of HLRSO- and HHO- resulted in a significantly diminished production of the arachidonic acid metabolites 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1alpha in stimulated platelets and aorta. Thus, high dietary levels of trans isomers of monoenoic acids do not interfere with platelet cyclooxygenase or lipoxygenase activity provided sufficient amounts of linoleic acid are available.

Animals↗

PubMed1983

Validation of radioimmunoassay for estradiol-17 beta by isotope dilution-mass spectrometry and by a test of radiochemical purity.

Isotope dilution-mass spectrometry (ID-MS) was used as a reference method to determine the concentration of estradiol-17 beta (E2) in five different plasma pools (concentrations ranging from 0.040 to 65 nmol/l). The same plasma pools were also subjected to radioimmunoassay (RIA) using five different antisera of largely varying specificity. With the best antiserum (E), a direct RIA apparently gave accurate results (i.e. results statistically indistinguishable from those obtained by ID-MS) at all levels except the lowest one (0.040 nmol/l). It was shown, however, that the apparent accuracy of this RIA to some extent could be due to a lowering effect of lipids in the serum masking a lack of specificity of the antibodies. With the least specific antiserum (A), accurate results were obtained only after chromatography. However, in the assay of the lowest concentration of E2 with this antiserum there was a significant overestimation, even after chromatography. The other three antisera (B, C, D) of average quality gave accurate results in assays of plasma diethyl ether extracts in various numbers of the plasma pools tested, depending on their intrinsic specificity. This specificity was not correlated with the cross-reaction reported for individual antisera. ID-MS is difficult to use in most laboratories. We demonstrate here that the validity of a RIA may in this case be assessed by a relatively simple method, the test of radiochemical purity (RP-test). This test is based on the measurements of specific activity (e.g. dpm/pg) in small consecutive fractions of the chromatographic zone which is usually employed for the RIA.

Estradiol↗

PubMed1982