Search PubMed⌕ Search

Biomedical subjects

H A Eder

Publications and source records attributed to H A Eder.

At least 37 records · Page 2Linked to original sources
PubMed1982

Cardiovascular complications.

This report summarizes the current state of knowledge concerning the cardiovascular system in various animal models of diabetes and presents their major strengths and weaknesses for studying the important research questions in the field. Nonhuman primates have many desirable features for studies on the macrovascular and cardiac complications of the disease as well as risk factor alterations, but their availability, cost, and maintenance present practical disadvantages. The spontaneous rodent models of diabetes currently are not considered very useful for cardiovascular research, but they have not been well characterized with respect to most aspects of their cardiovascular system. Alloxan-diabetic rabbits offer some promise for examining the effects of diabetes on atherogenesis, lipoprotein metabolism, and cardiomyopathy, but additional research is required to validate their usefulness. Insufficient data are available on canine and swine models of diabetes to judge their merits for cardiovascular research. The Task Force recommends: (1) additional longterm investigations to determine the extent and severity of cardiovascular complications in the well-characterized rodent models and in diabetic rodents with multiple risk factor abnormalities; (2) further studies on the macrovascular disease and lipoprotein abnormalities of the alloxan-diabetic rabbit and the development of rabbit colonies with spontaneous diabetes; (3) increased emphasis on such potentially important but neglected areas of research in diabetic animals as the intramyocardial circulation, adventitial blood vessels, blood pressure, platelet function, blood coagulation, blood rheology, and autonomic nervous function; (4) long-term studies on the influence of control of hyperglycemia and of insulin therapy on cardiovascular complications in diabetic animals; and (5) encouragement of use of diabetic nonhuman primates for cardiovascular research and institution of measures to increase their supply and availability by expanding current colonies, screening newly imported animals for diabetes, and establishing a visiting scientist's program allowing investigators to study diabetic primates at resource centers.

Animals↗
PubMed1982

Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure.

Studies in recent years have suggested that measurement of high density lipoprotein (HDL) subclasses may provide significant information beyond that provided by measurement of total HDL. However, conventional methodology for separation of HDL subclasses involves various types of ultracentrifugation that are time-consuming, costly, and not suitable for many clinical or epidemiological studies. We have developed a simple precipitation method for the separation of HDL subclasses in human plasma. After precipitation of apoB-containing lipoproteins with heparin-Mn2+, HDL2 is precipitated by addition of dextran sulfate (mol wt 15,000). HDL2 cholesterol is calculated as the difference between total HDL cholesterol (heparin-Mn2+ supernatant) and HDL3 cholesterol (dextran sulfate supernatant). HDL2 determined by this method correlated well with results obtained by preparative ultracentrifugation (n = 295, r = 0.91) and analytical ultracentrifugation (n = 17, r = 0.92). In the original method final concentration of dextran sulfate was 0.09 g/dl; however further studies indicated that 0.13 g/dl is a more suitable concentration. The chemical compositions of HDL2 and HDL3 isolated by the precipitation method were very similar to those of HDL2 and HDL3 isolated by preparative ultracentrifugation. The concentration of HDL2 cholesterol was 40% higher in normal women than in normal men. In men with coronary heart disease, total HDL was decreased by 28%, HDL2 was decreased by 44%, while HDL3 was 19% lower. A similar pattern of change was found in women with coronary heart disease. In other conditions where total HDL either increased or decreased, the change in HDL2 was always proportionately greater than the change in total HDL. HDL3 showed relatively less change, and in some instances its concentration was unchanged. Thus HDL2 is the more variable component and may be a more meaningful index of altered HDL metabolism.

Chemical Phenomena↗
PubMed1981

Comparison of the effects of colestipol hydrochloride and clofibrate on plasma lipids and lipoproteins in the treatment of hypercholesterolemia.

The effects of colestipol HCl resin and clofibrate on plasma lipid and lipoprotein levels were compared in 65 patients with primary hypercholesterolemia. Patients were randomly assigned to treatment with colestipol (in progressive doses of 15, 20, and 30 g/day), clofibrate (2 g/day), or placebo resin; lipoprotein levels were determined at months 0, 2, 4, 6, and 9. The colestipol group received both colestipol and clofibrate during months 7 through 9 of the study. After 6 months of treatment, mean plasma total cholesterol fell from 333 to 266 (P less than 0.01) on colestipol, and from 329 to 270 (P less than 0.05) on clofibrate. More patients responded, however, to colestipol than to clofibrate. Both drugs also produced significant reductions in LDL cholesterol levels, and clofibrate lowered plasma triglycerides as well. HDL cholesterol level did not change significantly on either medication. The placebo group showed no change in any of the parameters studied. A significant difference was not observed between the effects of 15 g/day of colestipol and those of the higher doses studies. Addition of clofibrate to colestipol did not enhance the latter's hypocholesterolemic action.

Cholesterol↗
PubMed1981

Hepatic binding and internalization of low density lipoprotein-gold conjugates in rats treated with 17 alpha-ethinylestradiol.

Receptor-mediated hepatic uptake of low density lipoproteins (LDL) conjugated to colloidal gold was studied by perfusion of livers from rats treated for 5 d with 17 alpha-ethinylestradiol. Estrogen treatment resulted in a marked decrease in serum lipid and lipoprotein concentrations. After 15 min of perfusion the conjugate was bound to the hepatic microvilli of both control and estrogen-treated rats; the estrogen-treated rats showed an 8- to 11-fold greater number of membrane-bound conjugates. The conjugates were bound to the membrane receptor by the LDL particle because the gold granules were regularly displaced from the membrane by 20 +/- 3.2 nm, the diameter of LDL. Internalization of the conjugate, evident by gold particles in multivesicular bodies, occurred at coated pits at the base of the microvillus where coated vesicles containing a single gold-LDL conjugate were released. After 1 h of perfusion, the livers from the estrogen-treated rats showed all phases of endocytosis and incorporation into multivesicular bodies of the conjugate. After 2 h of perfusion, there was congregation of gold-labeled lysosomes near the bile canaliculi. Gold-LDL conjugates were also observed to bind and be internalized by Kupffer cells and sinusoidal endothelium. These findings indicate that estrogen treatment induces hepatic receptors for LDL. The catabolic pathway of binding and endocytosis of the conjugate is similar to that seen in fibroblasts, although slower. Because gold-LDL conjugates were also present in the Kupffer and endothelial cells, the uptake of LDL by the liver involves the participation of more than a single cell type.

Animals↗
PubMed1980

Effects of 17 alpha-ethinyl estradiol on the serum lipoproteins of cholesterol-fed diabetic rats.

Large doses of 17 alpha-ethinyl estradiol were administered to rats made diabetic by administration of streptozotocin and fed a diet containing 2% cholesterol and 1% cholic acid. Before estrogen treatment, these rats were severely hypercholesterolemic and had high concentrations of lipoproteins of d < 1.006 g/ml (very low density lipoproteins, VLDL), d = 1.006 to 1.03 g/ml (intermediate density lipoproteins, IDL), and d = 1.03 to 1.063 g/ml (low density lipoproteins, LDL), and low concentrations of lipoproteins of d = 1.063 to 1.21 g/ml (high density lipoproteins, HDL). The VLDL contained two populations of particles with a mean diameter of 1150 and 350 A, respectively. The IDL contains only the latter particles. These particles are unusual in that they contain apolipoprotein A-I in addition to their usual complement of apolipoproteins. After estrogen treatment, the concentrations of both large and smaller particles in VLDL were greatly decreased as were the concentrations of IDL and LDL; apo A-I was no longer present in the residual VLDL and IDL. HDL phospholipid, protein, and cholesterol increased 7-fold, 4-fold, and 2-fold, respectively. Studies by others have shown that large doses of estrogen enhance uptake of LDL by the liver and this is associated with an increase in the saturable binding sites for LDL on liver membranes. The present studies suggest that these binding sites recognize lipoproteins other than LDL. Furthermore, the enhanced uptake of these lipoproteins appears to result in transfer of their surface components to HDL.

Animals↗
PubMed1980

Serum lipoproteins of diabetic rats fed a high cholesterol diet.

Feeding a diet containing 2% cholesterol and 1% cholic acid (wt/wt) to rats made diabetic by administration of streptozotocin (45 mg/kg) produced marked hypercholesterolemia characterized by high concentrations of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) and a reduction in concentration of high density lipoproteins (HDL). The VLDL was unique in that it contained apo A-I and apo A-IV in addition to its usual complement of apoproteins: apo B, apo E, and the C apoproteins. IDL had a similar apoprotein composition. The HDL from these rats was deficient in apo E. Nondiabetic rats fed the same diet exhibited similar qualitative changes in lipoprotein concentration and composition but with lesser increases in VLDL and IDL concentrations. The altered apoprotein composition suggested that the hyperlipoproteinemia associated with cholesterol feeding in the rat is due to an inadequate rate of removal of lipoproteins of intestinal origin, and that this is greatly exacerbated by diabetes.

Animals↗
PubMed1979

Biochemical and morphologic studies on diabetic rats: effects of sucrose-enriched diet in rats with pancreatic islet transplants.

Isolated pancreatic islets were administered to Lewis rats with streptozotocin-induced diabetes. Then the rats were fed either a semisynthetic diet containing 60% (wt/wt) sucrose for 3 weeks or were continued on chow. Transplantation resulted in a decrease in serum glucose, an increase in serum insulin, and a marked decrease in serum triacylglycerol, particularly in the sucrose-fed diabetic rats. In these rats, in demarcated areas of hepatocytes surrounding portal vein termini, lipid was deposited in the cytosol and large lipoprotein particles engorged the Golgi apparatus, Golgi-derived secretory vacuoles, and GERL. This model permits observation of the effects of pancreatic islet hormones on lipogenesis by hepatocytes in situ.

Animals↗
PubMed1979

Apoproteins of high density lipoproteins in the urine of normal subjects.

Apoproteins of high density lipoproteins were detected in the urine of normal subjects after the urinary proteins were highly concentrated. By immunoelectrophoresis, all of the urinary apoproteins gave precipitin lines with similar electrophoretic mobility. This suggests that the various apoproteins are present in the same particle. The apoproteins were present only in the ultracentrifugal fraction of density greater than 1.24 g/ml. Neither apoprotein B nor apoprotein E were detected in the urine, suggesting that very low density and low density lipoproteins are not excreted in the urine of normal subjects.

Apolipoproteins↗
PubMed1977

Characterization of the apolipoproteins of rat plasma lipoproteins.

Purified fractions of three major rat high-density lipoproteins (HDL) and one rat very low-density lipoprotein (VLDL) were isolated by Sephadex gel chromatography or preparative sodium dodecyl sulfate gel electrophoresis. These proteins were characterized by amino acid analysis, end-group analysis, molecular-weight determination, polyacrylamide gel electrophoresis, and circular dichroism. One of these rat proteins, of molecular weight 27 000, appears to be homologous with the human A-I protein. However, rat HDL possesses two additional major components not reported in human HDL - an arginine-rich protein of molecular weight 35 000 and a protein of molecular weight 46 000. The arginine-rich protein of the rat is similar in size and amino acid analysis to the arginine-rich protein reported in human VLDL. A major component of rat VLDL of 35 000 molecular weight appears similar or identical to the arginine-rich protein in rat HDL by every criterion employed for their characterization.

Amino Acid Sequence↗
PubMed1976

Serum lipoproteins and apolipoproteins in rats with streptozotocin-induced diabetes.

The lipoproteins of rats fed a high sucrose diet and made diabetic by administration of 45 mg/kg of streptozotocin were studied. All lipoprotein classes were found to be present in increased concentrations. The apolipoprotein composition of the various lipoprotein fractions was studied by polyacrylamide-gel electrophoresis in the presence of 8 M urea, isoelectric focusing in the presence of 8 M urea, and sodium dodecyl sulfate gel electrophoresis in polyacrylamide gels. In the very low density lipoproteins (VLDL) of diabetic rats, there was a marked alteration in the relative amounts of C proteins by polyacrylamide-gel electrophoresis, and this was found by isoelectric focusing to be primarily a relative increase in C-III-3 apoprotein and a decrease in C-III-O. In addition, in the diabetic rats, the VLDL contained a protein of mol wt 46,000, the A-IV protein, which normally is only present in the high density lipoproteins. In the high density lipoproteins, (HDL) the same alterations in pattern of the C proteins seen in the VLDL were present. Furthermore, the arginine-rich and A-IV protein normally present in HDL could not be detected in the HDL, although the other apolipoproteins are present. Apolipoprotein concentrations were determined by quantitative immunoelectrophoresis. It was found that in the diabetic rats there was an increase in the total amount of apo-B in the plasma, with the increment divided proportionately between the VLDL and the low density lipoprotein (LDL). The total apo-C concentration of plasma increased minimally. The A-IV concentration of plasma increased by 27%; it decreased markedly in the HDL, but appeared in increased amounts in both VLDL and in the d greater than 1.21 fraction. The arginine-rich protein decreased by 63% in the plasma and decreased significantly in the HDL, but increased in VLDL, LDL, and in the d greater than 1.21 fraction. These alterations in apolipoprotein patterns in diabetic animals suggest that the apolipoproteins may play an important role in determining the concentration of various lipoprotein fractions, or may be the result of altered metabolism of the lipoproteins. These lipoproteins with altered apolipoprotein composition may have important biologic differences from normal lipoporteins. Nevertheless, the HDL, despite the fact that it is deficient in some of its major constituents, was unchanged in its cholesterol content.

Animals↗
PubMed1976

Hyperlipoproteinemia in streptozotocin-treated rats.

In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal dose of streptozotocin was 45 mg/kg body weight for the sucrose-fed rats. With this dose, plasma glucose reached a maximum of over 600 mg/100 ml., and plasma insulin was reduced by 60 per cent. Plasma triglycerides rose in the sucrose-fed rats to over 1,000 mg/100 ml. two days after the streptozotocin was given and then decreased to over 770 mg./100 ml. 12 days after treatment and then to 585 mg./100 ml. 10 weeks after induction of diabetes. With this dose, ketonuria did not occur nor did any of the animals die, as occurred with higher doses. In the chow-fed rats, plasma triglyceride levels were elevated with the induction of diabetes to levels of approximately 300 mg./100 ml. The concentration of all the plasma lipoproteins increased with the induction of diabetes. The concentration of very-low density lipoprotein (VLDL) protein in the sucrose-fed diabetic increased fivefold, the low-density lipoprotein (LDL) protein increased, and especially striking was the increase in high-density lipoprotein (HDL) protein concentration, which became more pronounced with the duration of the diabetes. The diabetes produced by streptozotocin administration to sucrose-fed rats, thus, provides a useful model for the study of the hyperlipoproteinemia of diabetes.

Animals↗
PubMed1973

Serum lipoproteins of normal and cholesterol-fed rats.

The density distribution of lipoproteins in rats fed chow or chow containing 1% cholesterol and 10% olive oil was studied. Lipoprotein fractions were prepared in the ultra-centrifuge between narrow density bands within the density range of 1.006-1.21 and were analyzed by chemical, electrophoretic, and immunological methods. In serum from normal rats there were three major lipoprotein fractions, with densities less than 1.006, 1.030-1.063, and 1.063-1.21. Almost no lipoprotein was found between d 1.006 and 1.030. Most of the low density lipoprotein appeared between a density of 1.04 and 1.05. In the density range 1.05-1.07, small amounts of both low density and high density lipoprotein were found. Feeding a diet high in cholesterol resulted in a marked increase in the concentration of lipoproteins of density less than 1.006, and a new lipoprotein fraction appeared between d 1.006 and 1.030; this fraction contained immunologically demonstrable low density and high density lipoproteins. In addition, there was a decrease in the high density lipoprotein fraction between d 1.070 and 1.21.

Animals↗
PubMed1972

Effect of clofibrate on lipoprotein metabolism in hyperlipidemic rats.

The effects of clofibrate administration were studied in rats made hyperlipidemic by the feeding of diets high in sucrose. Within 12 hr of administration of clofibrate, there was a marked decrease in the concentration of serum high density lipoproteins but no change in the concentrations of the low and very low density lipoproteins. Between 2-4 days of treatment, the concentration of the very low density lipoproteins decreased whereas that of the low density lipoproteins was unchanged. In addition, the composition of the very low density lipoproteins was altered by clofibrate administration with a decrease in triglyceride and an increase in phospholipid content. The synthesis of high density lipoproteins, as measured by the incorporation of labeled amino acids, decreased within 12 hr of treatment. The synthesis of the very low density lipoproteins was increased during the first 2 days and then decreased slightly. The synthesis of low density lipoproteins did not change. The rate of removal of very low density lipoproteins was measured at various times from 0.5 to 8 days of treatment and was found to be elevated. It was concluded that in the hyperlipidemic sucrose-fed rat, administration of clofibrate results in a reduced level of very low density lipoproteins which may be due in part to enhancement of the rate of removal of this fraction.

Animals↗