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Biomedical subjects

G Friedman

Publications and source records attributed to G Friedman.

At least 181 records · Page 10Linked to original sources

Concurrent and subsequent serum cholesterol of breast- and formula-fed infants.

Animal studies have suggested that feeding a high-cholesterol diet early in life will reduce serum cholesterol of later life. We tested this hypothesis by comparing the serum cholesterol of breast-fed children and bottle-fed children. The former type of feeding has a cholesterol content 26-52 mg of cholesterol/8 ounces, and the latter type of feeding has 4 mg/2 ounces. Serum cholesterols were determined by the Wybenga technique. At the end of 4-6 months, both groups were switched from their original feeding to skim milk. The parents were counseled to avoid high-cholesterol content foods such as eggs and to limit the intake of the more moderate cholesterol dietary forms. Our objective was to achieve a cholesterol intake of 200 mg/day for both groups. The serum cholesterol was evaluated at the following ages: 2-4 months, 12 months, 18-24 months, and 15-19 years. The same child was not necessaryily followed longitudinally. Our results indicate that breast-fed children had significantly higher serum cholesterols than bottle-fed children at ages 2-4 months and 12 months. After 1 year, no significant difference in serum cholesterol was found when the two groups were compared. We concluded that no protection against high serum cholesterol in later life occurred as the result of initial feedings high in cholesterol.

Adolescent↗

Apolipoprotein Eepsilon4 allele, a risk factor for late onset nonfamilial Alzheimer's disease among Israeli Jews.

Apolipoprotein (apoE) genotypes were determined in 90 Israeli Jews with late onset sporadic Alzheimer's Disease (AD) and in 90 age- and sex-matched non-demented controls. The percentage of subjects carrying at least one apoEepsilon4 allele was 6% among the controls, and 42% among the patients (P<0.001), indicating a strong association between late onset sporadic AD and the apoEepsilon4 allele. However, no association was found between the apoEepsilon4 allele in demented and non-demented Jewish Israeli patients with Down's syndrome or Creutzfeldt-Jakob disease (CJD). The data presented in this paper confirmed several recent reports, suggesting that the apoEepsilon4 allele is a risk factor for the development of AD but not for the development of CJD or Down's syndrome among Israeli Jews.

Journal Article↗

Intestinal absorption of low molecular weight heparin in animals and human subjects.

INTRODUCTION: We had previously shown that the use of bile salts, which act as surfactants, facilitates the intestinal absorption of large molecules such as those of heparin and insulin. However, the bioavailability of unfractionated heparin (UFH) administered through the large intestine was low. The aim of the present study was to evaluate the absorption of low molecular weight heparin (LMWH) combined with bile salts through the gut mucosa in animals and human subjects. MATERIALS AND METHODS: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH with or without sodium cholate (Sch) was administrated rectally in rats and healthy volunteers via a microenema. Absorption was estimated by the activated partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the plasma lipoprotein lipase (LPL) activation. RESULTS: In groups of 6 rats, LMWH at doses of 100--1,000 U with sodium cholate (10--20 mg/ml) was readily absorbed through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1 U/ml and a dose-dependent activation of LPL. The absorption was significantly superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The plasma anti-factor Xa levels in the 6 healthy volunteers who received a microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15 min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also observed in these subjects. The plasma LMWH levels after rectal application were in the same range as those obtained after subcutaneous administration, however the elimination time (t 1/2) was shorter. There were no adverse reactions. CONCLUSIONS: Intestinal absorption of LMWH facilitated by Sch is both feasible and safe. A slow release formulation will be needed to prolong the plasma half-life.

Administration, Rectal↗

Expression of lipoprotein lipase mRNA in rat heart is localized mainly to mesenchymal cells as studied by in situ hybridization.

The expression of lipoprotein lipase mRNA (LPL mRNA) was studied in rat hearts by use of a sulfur-35-labeled antisense mRNA probe. Rats were studied under three conditions: fed, fasted, and injected with cholera toxin (an irreversible agonist of adenylate cyclase) and then fasted. The highest LPL activity was found in the hearts of cholera toxin-injected, fasted rats. After injection of cholera toxin, LPL mRNA levels were 3.5-fold higher than those from fed rats. Using in situ hybridization, we studied the site of expression of LPL mRNA under the same three experimental conditions. In sections of hearts from cholera toxin-injected, fasted rats, concentrations of autoradiographic grains, representing the site of LPL mRNA, were seen over interstitial elements, which comprise capillary and perivascular cells. A more diffuse and sparse reaction was seen over cardiac myocytes and was not always distinguishable from background. A similar but much less definitive localization was seen in sections of hearts from fasted rats. The present results indicate that in the rat heart, the main site of LPL synthesis and processing, especially after stimulation with an irreversible agonist of adenylate cyclase, is localized to interstitial elements rather than to adult cardiac myocytes.

Adenylyl Cyclase Inhibitors↗

Enhanced metabolism of normolipidemic human plasma very low density lipoprotein in cultured cells by exogenous apolipoprotein E-3.

In this investigation in cultured human fibroblasts, an attempt was made to determine the optimal metabolism of apolipoprotein (apo) B-100 lipoproteins from normolipidemic human subjects. We supplemented culture systems containing 125I-lipoproteins with exogenous recombinant or plasmatic apo E-3. Very low density lipoprotein (VLDL) fractions I, II, and III, and low density lipoproteins (LDL) were prepared from one E 4/3 and four E 3/3 subjects. Without added apo E-3, cellular metabolism (binding, cell association, and degradation) of VLDL-I, II, and III was negligible. Exogenous apo E-3 caused a many-fold enhancement of the metabolism of the three VLDL fractions, but LDL was not affected. The effects of apo E-3 were specific, not observed with apo E-2, and not observed on receptor-negative cells. Exogenous apo E-3 also enhanced down-regulation of cellular sterol synthesis by the VLDLs, but not LDL, indicating increased particle catabolism by the cells. The optimal concentrations of exogenous apo E-3 were 4 to 6 micrograms protein/15 micrograms VLDL-protein, when most of the added apo E-3 became associated with the VLDL particles. Apo E-3 failed to associate with LDL. These results demonstrate that availability and association of adequate amounts of apo E-3 are crucial for optimal cellular metabolism of apo B-100 lipoproteins along the VLDL----LDL cascade.

Apolipoprotein E3↗