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Biomedical subjects

J Beitz

Publications and source records attributed to J Beitz.

At least 73 records · Page 4Linked to original sources

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↗

Influence of a cod liver oil diet in diabetics type I on fatty acid patterns and platelet aggregation.

The influence of an eicosapentaenoic acid rich diet containing only 6,8 g cod liver oil daily for 2 weeks in 20 type I diabetics on fatty acid pattern in serum, platelet aggregation and thiobarbituric acid-reactive substances in serum were studied. There were increases in eicosapentaenoic acid portions in triglycerides, cholesterol esters and phospholipids of serum. This was associated with an inhibition of the platelet hyperaggregation, whereas platelet hyporeactivity is shifted to normal. Hyperreactivity of platelets from diabetics may be caused by enhanced TXA2 formation in comparison to healthy humans (1). On the other hand, diets rich in eicosapentaenoic acid inhibit platelet aggregation in healthy Volunteers (2,3). Therefore we investigated the dietary effect of relatively low doses of cod liver oil in diabetics type I on the eicosapentaenoic acid/arachidonic acid balance.

Adult↗

Thromboxane B2 (TXB2) formation in clotting whole blood of healthy and diabetic humans in vitro.

We investigated the ability of platelets from two groups of diabetics type I and two groups of healthy volunteers matched of age to generate thromboxane B2 (TXB2) during spontaneous clotting of whole blood. The serum concentration of TXB2, reflecting the ability of the platelets to generate TXA2 during clotting, was measured by gas liquid chromatography. Platelets from old diabetics with more than 40 years duration of diabetes mellitus formed significantly less TXB2 than those from old healthy controls. Platelets from juvenile diabetics (9 years duration of disease) formed nearly the same amount of TXB2 as those from young healthy volunteers. The importance of these results is discussed.

Adult↗

The influence of linseed oil diet on fatty acid pattern in phospholipids and thromboxane formation in platelets in man.

Ten healthy volunteers daily received 30 ml linseed oil for 4 weeks in addition to the "normal" diet. The influence of linseed oil diet on the fatty acid pattern of plasma phospholipids and thromboxane formation in platelets was investigated. The fatty acid pattern was analysed by gas liquid chromatography. The alpha-linolenic, eicosapentaenoic and docosahexaenoic acids were increased (p less than 0.01), whereas linoleic and arachidonic acids were decreased (p less than 0.05) after 4 weeks of the linseed oil diet. The thromboxane formation of platelets were unchanged. Additionally the influence of HDL and LDL on PGI2 biosynthesis in pig aortic microsomes (PAM) was investigated. HDL taken from serum before and after 3 weeks of linseed oil diet and LDL taken after 3 weeks of diet stimulated the PGI2 formation in PAM, whereas LDL taken from serum before the diet period inhibited the PGI2 formation in PAM.

6-Ketoprostaglandin F1 alpha↗

Inhibition of prostaglandin I2 (PGI2) formation by LDL-cholesterol or LDL-peroxides?

A hypothesis of Gryglewski et al. explains the correlation between increased level of LDL and development of atherosclerosis by inhibition of PGI2 synthesis by increased peroxide content of LDL. The aim of the present paper was to examine this hypothesis. The major results are: 1) Preparation of LDL in the presence of .02% butylated hydroxytoluene did not reduce the lipid peroxide content of LDL from men and women and not change the inhibition or stimulation of the in vitro biosynthesis of PGI2 by LDL isolated from blood of men or women, respectively. 2) In the LDL and HDL, respectively, of healthy men we found nearly the same lipid peroxide levels (nmole malondialdehyde (MDA)/mg lipoprotein-cholesterol) as in the lipoproteins of male patients with hyperlipidemia type IIa or IV, but the peroxide concentration is three times higher in HDL as in LDL. 3) LDL isolated from healthy men inhibited in dose dependent fashion the generation of PGI2 from PGH2 by aortic microsomes whereas LDL from premenopausal women stimulated PGI2 formation even calculated as LDL lipid peroxides (in nM MDA/ml). The results call into question the hypothesis that diminished PGI2 formation by atherosclerotic vessels is related to inhibition of PGI2 synthetase by lipid peroxides present in LDL in the lesions. A new working hypothesis is presented that also the fatty acid pattern and the lipid class composition in the LDL are important for their influence on the PGI2 formation.

Animals↗

Low density lipoprotein (LDL) from male volunteers stimulated the thromboxane formation by human platelets.

LDL (0.5 - 2.0 mg LDL-cholesterol/ml) isolated from venous blood of healthy male volunteers stimulated dose-dependently the malondialdehyde (MDA) formation by frozen human platelets, used as a marker for the activity of the thromboxane synthetase. HDL (0.25 - 1.0 mg HDL-cholesterol/ml) and human serum albumin (1 - 10 mg/ml) had no concentration-dependent influence on the MDA formation. If these results can be extended to in vivo they suggested the strong connection between the prostaglandin and lipoprotein hypothesis of pathogenesis of atherosclerosis.

Adult↗

Alterations in renal and aortic prostaglandin E and F formation correlate with blood pressure dietary linoleate deficiency.

Male Wistar rats received for 4 weeks a linoleic acid (LA) rich (13.3 cal. % LA) or an LA deficient (0.5 cal. % LA) diet as well as 1.5% sodium chloride as drinking fluid. Compared with the LA rich diet the LA deficient diet caused an increase in blood pressure of about 10 mmHg. Indomethacin treatment (2 X 1 mg/kg/day s.c.) increased the blood pressure in the LA rich but not in the LA deficient fed rats. The flow rate of isolated perfused kidneys was reduced after 4 weeks LA deficient diet as were aortic and renal PGE formation, whereas PGF formation was only slightly diminished. PGE2 degradation in the kidney was not influenced by the LA content of the diet. We postulate that the prohypertensive effect of LA deficient diet in salt loaded rats is mediated via a reduction of endogenous PGE formation and a shift towards PGF.

Animals↗

Differential influence of lipoproteins isolated from women and men on the activity of the PGI2 synthetase activity.

We have found a correlation between the activity of the PGI2 synthetase in the microsomal fraction of pig aorta and the amount of high density lipoprotein (HDL) cholesterol in the incubation fluid. The reverse was true for low density lipoprotein (LDL) cholesterol. These correlations exist independently of whether the lipoproteins were isolated from men than from women as it is for HDL isolated from women than from men. This result may give an explanation for the differential risk against the incidence of cardiovascular disease between women and men at the same concentration of the individual lipoproteins in their blood.

Animals↗

Cholesterol esters of rat hearts of linoleic acid fed rats stimulate prostaglandin I2 (PGI2) synthetase activity.

Rats fed a diet rich or poor in linoleic acid (LA) for 25 weeks were used for investigation into whether the cholesterol ester (CE) of rate hearts influences the conversion of PGH2 to PGI2 by the microsomal fraction of pig aorta. The CE of rats fed the LA rich diet increased PGI2 synthesis after 4 weeks and even more after 25 weeks, whereas CE from rats fed the LA poor diet decreased PGI2 synthetase activity.

Animals↗

Influence of linseed oil diet on the pattern of serum phospholipids in man.

We gave 11 volunteers 30 ml linseed oil daily for 4 weeks. This diet increased the amount of linolenic, eicosapentaenoic and docosahexaenoic acid in the serum phospholipids within 1 week, whereas the amount of dihomo-gamma-linolenic acid was decreased. Both effects were statistically significant. The results suggest that eicosapentaenoic acid can be synthesized from alpha-linolenic acid in human organism.

Adult↗

Influence of human low density and high density lipoprotein cholesterol on the in vitro prostaglandin I2 synthetase activity.

We investigated in vitro the influence of low density lipoprotein (LDL) cholesterol and high density lioprotein (HDL) cholesterol separated from human serum on prostaglandin I2 synthetase activity studied by the conversion of prostaglandin H2 to prostaglandin I2 by the microsomal fraction of pig aorta. 6-Oxo-prostaglandin F1 alpha was analyzed by gas-liquid chromatography using prostaglandin F1 alpha as internal standard. We found a linear negative correlation (P less than 0.001) between the amount of LDL cholesterol in the incubation solution and prostaglandin I2 synthetase activity, whereas there was a positive correlation (P less than 0.01) between HDL cholesterol and prostaglandin I2 synthesis. A very low concentration of LDL cholesterol and a high concentration of HDL cholesterol stimulated prostaglandin I2 synthesis, whereas a high LDL cholesterol concentration inhibited prostaglandin I2 biosynthesis by 64%. The concentration range of LDL and HDL cholesterol was representative of physiologically low, normal or elevated levels of lipoproteins.

Animals↗

Catalytic properties and electrostatic potential of charged immobilized enzyme derivatives. Pyruvate decarboxylase attached to cationic polystyrene beads of different charge densities.

Pyruvate decarboxylase has been covalently attached to positively charged macroporous polystyrene resins. The changes in the functional behaviour of the enzyme resulting from the electrostatic interaction of the cationic carrier polymer and the anionic substrate have been studied as function of the fixed charge concentration of the carrier. The findings confirm the connection of two widely used theoretical expressions relating electrostatic parameters with Michaelis constants.

Carboxy-Lyases↗

Stimulation and inhibition of PGI2 synthetase activity by phospholipids (PL), cholesterol esters (CE), unesterified fatty acids (UFA) and lipoproteins (LDL and HDL).

We investigated the influence of different lipids on the transformation of PGH2 to PGI2 by the microsomal fraction of pig aorta. Phospholipids and cholesterol esters obtained from animals fed prenatally a linoleic acid rich diet stimulated the PGI2 formation. However, when obtained from animals fed prenatally a linoleic acid deficient diet, phospholipids and cholesterol esters inhibited PGI2 production. Unesterified fatty acids are potent inhibitors at 1 mM. The degree of inhibition was dependent on the length of the carbon chain and the number of double bonds in the UFA molecule. We found further that lipoproteins modified the PGI2 formation at physiological concentrations. The amount of hig density lipoprotein cholesterol had a positive correlation with the activity of PGI2 synthetase, whereas the amount of low density lipoproteins cholesterol had a negative one.

Animals↗

[Effect of the chemical surface structure of functionalized polystyrene on the kinetic properties of immobilized yeast pyruvate decarboxylase].

The influence of the loading density of different functional groups and the length of suitable spacer structures on the kinetic properties of yeast pyruvate decarboxylase are investigated on identical polystyrene matrices. At constant concentrations of the fixed protein both the specific activity and the storage stability of the immobilized enzymes increase with increasing concentrations of the protein binding (C = O)-groups. pH-Optimum and K'M-value prove to be functions of the NH3+-content of the supports. Using four spacer resins with an equal content of spacer groups it could be shown that the optimum time of coupling as well as the maximum catalytical activity, storage stability and thermostability depend on the length of the spacer structures. On the other hand, the mobility of an ESR-marker fixed via the same spacers to the resin is not affected by the different spacer structures.

Carboxy-Lyases↗

Trapidil derivatives and low density lipoprotein metabolism by human skin fibroblasts and by human hepatoma cell line Hep G2.

The effect of trapidil (RocornalR) and some of its newly developed derivatives (AR 12456, AR 12463, AR 12465, AR 12464) on the receptor-mediated low density lipoprotein (LDL) binding, uptake and degradation was studied in human skin fibroblasts (HSF) and in human hepatoma cell line Hep G2. Compound AR 12456 influenced this pathway in a selective way: it enhanced the uptake and degradation of 125I-LDL by Hep G2 cells in a dose-dependent manner, but inhibited it in HSF. Scatchard analysis of the saturable LDL binding in Hep G2 indicates that the effect of compound AR 12456 is the result of an increased number of LDL binding sites. Compound AR 12465 was less effective on LDL catabolism. Trapidil and the other derivatives were inactive under the same experimental conditions. When Ar 12456 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. These findings suggest that a metabolite(s) of AR 12456 might be responsible for the enhanced expression of LDL receptors in cultured human cells.

Animals↗