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Biomedical subjects

U Cogan

Publications and source records attributed to U Cogan.

At least 19 recordsLinked to original sources
PubMed1992

Lovastatin inhibits low-density lipoprotein oxidation and alters its fluidity and uptake by macrophages: in vitro and in vivo studies.

Under experimental conditions, oxidized low-density lipoprotein (Ox-LDL) may possess atherogenic properties, as is evidenced by its contribution to cholesterol accumulation in macrophages. LDL was oxidized in a cell-free system by predialysis of the lipoprotein against EDTA-free buffer and the addition of copper ions. Oxidation of LDL in the presence of lovastatin (10 to 1,000 mumol/L) resulted in a time- and dose-dependent reduction in thiobarbituric-acid-reactive substances (TBARS) concentration that was accompanied by increased LDL lysine-amino-group reactivity, in comparison with Ox-LDL produced in the absence of lovastatin. At 100 mumol/L, the drug reduced malondialdehyde concentration and increased amino-group reactivity by 24% and 42%, respectively. However, lovastatin's antioxidant effect was limited relative to other antioxidants, such as probucol and vitamin E. The fluidity of Ox-LDL was substantially reduced in comparison with native LDL. However, lovastatin inhibited this reduction in fluidity by 20%. Upon incubation of J-774 macrophage-like cell line with Ox-LDL, the lovastatin-treated Ox-LDL induced a reduction in the cellular cholesterol esterification rate in comparison with the effect of Ox-LDL that was produced in the absence of the drug. In four patients with hypercholesterolemia, the effect of lovastatin therapy (20 mg/d) on the sensitivity of their LDL to in vitro oxidation was studied. In all patients, Ox-LDL prepared from LDL obtained during lovastatin treatment demonstrated a reduced TBARS content, an increased trinitrobenzenesulfonic acid (TNBS) reactivity, an increased fluidity, and an impaired uptake by macrophages. These results were similar to those obtained by adding lovastatin in vitro.

Animals↗
PubMed1992

Food restriction and membrane fluidity.

The fluidity of the erythrocyte membrane derived from growing rats raised under restricted food intake was found to be higher than the fluidity of the respective membranes from ad libitum fed animals. Considering the apparent relationship between the decrease in membrane fluidity and aging, the results point to the possible beneficial effects of food restriction at a young age.

Aging↗
PubMed1992

Dietary fish oil modulates the alkaline phosphatase activity and not the fluidity of rat intestinal microvillus membrane.

The effect of dietary fish (mackerel) oil on the function and fluidity of the intestinal microvillus membrane in 1-y-old rats was compared with that of coconut and soybean oils. The animals were fed diets containing 10% protein (derived from casein) and 15% oil. Intestinal microvillus membranes and RBC ghosts were isolated after a 6-wk feeding period and examined for fluidity by fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene. The functionality of the microvillus membrane was assessed by the activity of the intrinsic enzyme alkaline phosphatase. No differences in the fluidity were observed between the microvillus membranes or between the RBC ghosts derived from the various dietary groups. The alkaline phosphatase activity of the microvillus membrane was found to be the lowest in the membranes isolated from the fish oil-fed rats. In these membranes the contents of 20:5(n-3) and 22:6(n-3) fatty acids were higher than in the membranes derived from the coconut and soybean oil-fed animals. The cholesterol to phospholipid molar ratio was lower in the coconut oil-fed group than in the other two groups. It is suggested that the compensatory effect of the elevated cholesterol to phospholipid molar ratio on the membrane fluidity was such that no differences in the overall fluidity were detected. It is likely that the incorporation of these long chain fatty acids might have caused compositional changes in the lipid microenvironment of the enzyme. Such changes could alter the fluidity of these microdomains, thereby affecting the activity of the integral enzyme alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1992

Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia.

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.

Adult↗
PubMed1992

Reduction of plasma cholesterol by lovastatin normalizes erythrocyte membrane fluidity in patients with severe hypercholesterolaemia.

The effect of lovastatin on erythrocyte membrane composition and fluidity was investigated in eight patients with severe hypercholesterolaemia (mean LDL-cholesterol of 7.2 mmol l-1). Lovastatin was administered at a dosage of 40-80 mg for 20 weeks and was discontinued for 5 weeks thereafter. Parallel to a 47% fall in plasma LDL cholesterol, there was a significant reduction (P < 0.01) in erythrocyte membrane cholesterol:phospholipid molar ratio, while erythrocyte membrane fluidity assessed by diphenylhexatriene (DPH) fluorescence polarization increased significantly (P < 0.01). Discontinuation of lovastatin resulted in the reversal of erythrocyte membrane composition and fluidity to pre-treatment values.

Adult↗
PubMed1991

Excessive dietary tryptophan enhances plasma lipid peroxidation in rats.

High plasma cholesterol levels and plasma lipid peroxidation are associated with atherosclerosis. The effect of excessive dietary tryptophan on plasma lipid peroxidation was studied in rats fed a diet containing soybean oil (control), as well as an atherogenic diet, containing coconut oil and cholesterol. Feeding the atherogenic diet resulted in a 5-fold increment in plasma cholesterol concentration with no significant effect of the tryptophan supplementation. The plasma obtained from the hypercholesterolemic rats exhibited a 67% increased lipid oxidation (measured as thiobarbituric acid reactive substances) in comparison to normocholesterolemic plasma. Dietary tryptophan supplementation increased plasma lipid peroxidation by 9 and 21% in the control and in the hypercholesterolemic animals, respectively. Similarly, the excessive dietary tryptophan enhanced macrophage cholesterol esterification rate by 40 and 38% following cell incubation with the plasma obtained from the control and from the hypercholesterolemic animals, respectively. Since tryptophan is the precursor of serotonin we have measured urine concentration of 5-hydroxyindoleacetic acid (5HIAA), the metabolite of serotonin, and found 22 and 118% elevation in 5HIAA in the tryptophan fed control and hypercholesterolemic rats, respectively. The direct effect of tryptophan and serotonin on in vitro lipid peroxidation was also studied. Low density lipoprotein (LDL) was peroxidized by incubation with copper ions in the presence of tryptophan or serotonin. Serotonin was shown to enhance LDL peroxidation whereas tryptophan had no effect on LDL peroxidation. We conclude that excessive dietary tryptophan may be atherogenic since it enhanced plasma lipid peroxidation in hypercholesterolemic rats and increased macrophage uptake of plasma cholesterol. These effects are probably associated with increased plasma concentration of serotonin following the consumption of a tryptophan supplemented diet.

Animals↗
PubMed1991

Decreased very low density lipoprotein fluidity in familial hypercholesterolemia.

The fluidity of lipoproteins from normolipidemic subjects and from familial hypercholesterolemic patients was investigated by fluorescence polarization. The fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene) was incorporated into the lipoprotein fractions, and assessment of the fluidity pattern of each particle was determined by fluorescence anisotropy measurements over a temperature range of 10 to 40 degrees C. The very low density lipoprotein (VLDL) of the hypercholesterolemic patients was found to be considerably more rigid than the respective VLDL of normolipidemic subjects. Analysis of the constituents of the various lipoproteins suggested that the large difference in the fluidity between hypercholesterolemic and normal VLDL patients might be due to increased VLDL cholesterol/triglyceride, cholesterol/protein and cholesterol/phospholipid ratios, which were 10, 2 and 1.4 fold higher, respectively, in the hypercholesterolemic VLDL patients. Decreased VLDL fluidity in familial hypercholesterolemic patients may be of importance in the pathogenesis of their accelerated atherosclerosis.

Adolescent↗
PubMed1990

Riboflavin deficiency and the function and fluidity of rat erythrocyte membranes.

The effect of riboflavin deficiency on the fluidity and function of the red blood cell (RBC) membrane and on the activity of some enzymes involved in antioxidant defense mechanisms was studied. Growing male rats were fed an experimental (riboflavin-deficient) or a control (riboflavin-supplemented) diet. Following 7 wk of feeding, RBC from riboflavin-deficient rats contained higher levels of peroxidation products, most likely due to decreased glutathione reductase activity. An elevation in glutathione peroxidase activity was also observed whereas the activity of catalase and superoxide dismutase was not affected. Membrane fluidity was studied by fluorescence polarization, using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. The fluidity of RBC membranes isolated from riboflavin-deficient rats was significantly lower than that of the controls. This decreased fluidity was accompanied by an increase in the activity of the membrane-bound enzyme acetylcholinesterase. This study demonstrated that a decrease in cells' ability to cope with peroxidative damage as a result of riboflavin deficiency may lead to changes in the fluidity and function of membranes.

Acetylcholinesterase↗
PubMed1990

Dietary tryptophan enhances platelet aggregation in rats.

The effect of diets enriched with tryptophan (4 and 10 g/kg) on ADP induced platelet aggregation and on plasma lipids was studied with growing rats, following feeding periods of up to 3 weeks. Dietary tryptophan was found to enhance markedly ADP induced platelet aggregation. It appears that this effect was not related to plasma lipid levels. In vitro studies aimed to clarify the mechanism by which tryptophan exerts its action showed that the latter, at concentrations up to 100 micrograms/ml, had no effect on ADP induced platelet aggregation. On the other hand, serotonin, the metabolic product of tryptophan, increased the ADP induced platelet aggregation in a dose dependent pattern. The possible involvement of serotonin in the observed enhancement of platelet aggregation was further substantiated by the observed high levels of 5-hydroxyindole acetic acid, which is a catabolite of serotonin, in the urine of the experimental animals. It is conceivable that tryptophan enhances platelet aggregation in rats via its metabolite, serotonin, and this may in turn contribute to increased atheroslerotic risk.

Adenosine Diphosphate↗
PubMed1989

Age and membrane fluidity.

Male rats aged 1, 9 and 19 months were used to study changes in membrane fluidity with age, employing the fluorescence polarization technique with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the fluorescent probe. The intestinal microvillus membranes derived from the 19-month-old rats were found to possess lower fluidity than that observed with the membranes derived from the younger animals. The decrease in fluidity with age was also reflected in a corresponding increase in the gel-to-liquid crystalline transition temperature. Only small insignificant changes with age, were observed in the fluidity of the red blood cell membrane.

Aging↗
PubMed1989

The safety evaluation of Dunaliella bardawil as a potential food supplement.

The safety of the alga Dunaliella bardawil for food use, was evaluated in a multigeneration study with rats. Four generations were raised on diets containing 0, 5 or 10% dehydrated D. bardawil. Each experimental group comprised ten males and 20 females. No significant differences were observed between the rats consuming algae and the controls, of any generation, in general appearance, behaviour, growth, reproductive performance or gross pathology. The blood chemistry and haematology of the first generation animals, after 1 yr on the diets, showed no appreciable differences between the experimental and control animals. The only differences in histopathology observed were a decrease in some chronic inflammations and an increased frequency of focal bronchopneumonia in rats fed 10% algae compared with the controls. The latter effect may be attributed to the powdery nature of the algal diet. Considering the large amount of algae consumed by the experimental rats, and the absence of adverse effects in these animals, this multigeneration feeding study may be indicative of the safety of D. bardawil for human consumption.

Animal Feed↗
PubMed1989

The thermal properties of intestinal alkaline phosphatase of three kinds of deep-water fish.

1. The thermal properties of intestinal alkaline phosphatase were investigated with three species of deep-water fish in the temperature range of 0-70 C. 2. A relationship was found between the thermal stability of the enzyme and the fish origin. 3. Maximum activity of alkaline phosphatase of the fish that originated in tropical water, namely, Aphanopus carbo and Epigonus telescopus was 60 C, whereas the respective maximum enzyme activity of Etmopterus princeps that originated in the burial zone was 30 C. 4. A breakpoint at 10 degrees C in the Arrhenius plot of emzyme activity in the case of A. carbo and a lack of a break point in the case of E. telescopus and E. princeps, are in accordance with the stenothermic nature of the former and the everythermic nature of the two latter fish species.

Alkaline Phosphatase↗
PubMed1989

An effective method for plasma lipoprotein separation: studies of various animal species.

1. Plasma lipoprotein separation by density gradient ultracentrifugation largely depends on visual examination based on the natural yellow pigments of lipoproteins. 2. In non-human species and in humans with dyslipoproteinemia, some lipoproteins are not well visualized due to the lack of pigments. 3. Using a fluorescent probe in minute quantity (1,6 diphenyl-1,3,5-hexatriene) we were able to demonstrate an effective plasma lipoprotein separation using a discontinuous density gradient ultracentrifugation technique. 4. Plasma lipoproteins of human, chicken, rat and carp were compared showing the unique character of carp HDL.

Animals↗
PubMed1987

Protein malnutrition and the function and fluidity of the intestinal microvillus membrane in growing rats.

The effect of protein malnutrition on the function, fluidity and composition of the intestinal microvillus membrane was studied in growing rats. Weanling male rats were fed diets containing 10% protein derived from either wheat gluten (experimental diet) or casein (control diet). Intestinal microvillus membranes were isolated after a 7-wk feeding period. The functionality of the membranes, as assessed by the level of activity of the four enzymes alkaline phosphatase, gamma-glutamyl transpeptidase, leucine aminopeptidase and maltase, showed no difference between the membranes derived from the experimental and the control animals. Similar Arrhenius plot patterns of alkaline phosphatase activity (13-50 degrees C) and of the fluorescence anisotropy parameter (8-40 degrees C) were observed for both types of membranes with respect to the transition temperatures and energies of activation. In addition, the similarity between the membranes derived from the experimental and the control animals was also manifested in the cholesterol and phospholipid content. The study demonstrates that despite the extreme nutritional stress exerted on the gluten-fed rats, the integrity and functionality of the intestinal microvillus membrane was adequately maintained.

Alkaline Phosphatase↗
PubMed1976

Comparative studies of human and chicken retinol-binding proteins and prealbumins.

Microheterogeneity of retinol-binding proteins of human plasma and urine, and of chicken plasma was studied by polyacrylamide gel electrophoresis. All three protein systems were found microheterogenous. Incorporation of retinol into the protein preparations on the one hand, and depletion of these proteins from retinol on the other hand, enabled us to clarify the extent to which the presence or absence of the ligand affects the apparent heterogeneity. Upon electrophoresis, each of the native proteins displayed two pairs of protein zones. It appeared that within each pair the fast moving band corresponded to aporetinol-binding protein which upon binding of retinol was converted to a holoprotein with a slightly lower mobility. However, it did not seem that proteins of one pair were converted to proteins of the second pair upon binding of retinol, substantiating ghe microheterogenous character of this protein system. A rapid, two step procedure for isolation of prealbumins from plasma is described. The method which consists of DEAE-cellulose chromatography follwed by preparative electrophoresis was utilized to separate human and chicken prealbumins. Routine dodecyl sulphate electrophoresis resulted in partial dissociation of human prealbumin but in no dissociation of the chicken protein. More drastic treatments prior to electrophoresis were needed to effect complete disruption of both proteins into subunits.

Animals↗
PubMed1976

The interaction between retinol-binding proteins and prealbumins studied by fluorescence polarization.

The interaction between retinol-binding proteins and prealbumins of human and chicken was studied by fluorescence polarization techniques. The binding affinity between chicken plasma retinol-binding protein and chicken prealbumin was essentially the same as between the respective human proteins. Human urine retinol-binding protein displayed a similar affinity, though possibly slightly smaller than that of the human plasma protein, toward human prealbumin. Retinol-binding proteins and prealbumins of human and chicken have been found to cross-interact displaying an affinity similar to that displayed by the proteins of the same species. Solution of a binding equation which assumes identical, independent sites, indicated that the number of binding sites on prealbumin for retinol-binding protein is somewhat less than 2 with the human system, and in the neighborhood of 4 with the chicken system. A possible interpretation suggests that prealbumin possesses four identical binding sites for retinol-binding protein, one for each subunit, but that the binding is of a negative cooperative nature. A major share of the negative cooperativity is likely to result from steric hindrance induced by already bound retinol-binding protein molecules, which have a sizable volume compared to the volume of the prealbumin molecule. The cooperativity is likely to be more pronounced with the human system. Rotational relaxation times derived from Perrin plots suggest that 1:1 molecular complexes of retinol-binding proteins with prealbumins have a compact structure.

Animals↗