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Biomedical subjects

I Weinstein

Publications and source records attributed to I Weinstein.

At least 19 recordsLinked to original sources
PubMed1993

Subtotal splenectomy for Gaucher's disease: a follow-up study.

Three patients with Gaucher's disease who underwent partial splenectomy have been followed for 3, 7 3/4, and 8 1/2 years. All have had significant regrowth of the the splenic remnant and some recurrence of hypersplenism. A review of all previously reported cases also substantiates the recurrence of splenomegaly and hypersplenism. Among new options for the therapy of Gaucher's disease, enzyme replacement therapy (Ceredase) holds great promise for effective treatment.

Female↗
PubMed1991

Secretion of triglyceride and ketogenesis by livers from spontaneous diabetic BB Wistar rats.

Livers from male and female BB Wistar spontaneously diabetic rats were perfused in vitro to determine the effects of spontaneously occurring insulin-dependent diabetes on the metabolism of fatty acid. The secretion of triglyceride and the incorporation of [1-14C] oleic acid into perfusate and hepatic triglyceride was reduced by the diabetic state, whereas beta-hydroxybutyrate production and output of total ketone bodies were increased. The spontaneous diabetic Wistar rat clearly is a suitable model to study the derangements induced in lipid/plasma lipoprotein metabolism by the insulin-dependent diabetic state; the data obtained with this model confirm our earlier observations on experimental insulin deficiency induced with alloxan, streptozotocin, and anti-insulin serum.

3-Hydroxybutyric Acid↗
PubMed1988

Effects of the antiestrogen LY 117018 on the modulation by ethinyl estradiol of the metabolism of [1-14C]oleic acid by perfused livers from normal and ovariectomized rats.

Intact female Sprague-Dawley rats (195-249 g) and rats that had been ovariectomized (210-285 g) were injected subcutaneously for 14 days with ethinyl estradiol (15 micrograms/kg), the antiestrogen LY 117018 (500 micrograms/kg), both drugs simultaneously, or the vehicle (sesame oil) alone. Livers were removed and perfused in vitro in a recycling system. The administration of LY 117018 alone did not affect the secretion of triacylglycerol by livers from normal rats but decreased the secretion of triacylglycerol by livers from ovariectomized rats. When the drugs were administered concurrently to either normal or ovariectomized animals, the increase in the concentration of triacylglycerol and the decrease in the concentration of cholesteryl esters in the plasma produced by ethinyl estradiol were prevented. When administered to either intact or ovariectomized rats, ethinyl estradiol alone stimulated the synthesis and secretion of triacylglycerol and cholesteryl esters by perfused livers isolated from these animals. The simultaneous administration of LY 117018 with ethinyl estradiol prevented this stimulation of the hepatic synthesis and secretion of triacylglycerol and cholesteryl esters. The depression of ketogenesis observed with livers from rats administered ethinyl estradiol alone was reversed by concurrent administration of LY 117018. The concurrent administration of the estrogen and antiestrogen did not result, however, in a complete blockade of the estrogen-induced elevation of hepatic triacylglycerol synthesis and depression of ketogenesis. The incorporation of [1-14C]oleic acid into the triacylglycerol and ketone bodies by livers from ovariectomized rats was less than that of livers from normal rats. It is clear that the antiestrogen antagonizes the actions of ethinyl estradiol on hepatic lipid metabolism. Furthermore, the use of the antiestrogen LY 117018 in these experiments allows the probable conclusion that the modulation of hepatic metabolism of fatty acid by estrogen is mediated by conventional estrogenic receptors.

Animals↗
PubMed1986

Regulation by oestrogen of carnitine palmitoyltransferase in hepatic mitochondria.

Treatment of female rats with ethynyloestradiol decreased both the activity of carnitine palmitoyltransferase and its Ki value for malonyl-CoA compared with pair-fed control rats. In starved rats, carnitine palmitoyltransferase activity and its Ki value for malonyl-CoA were both elevated as expected. Oestrogen treatment had no effect on carnitine palmitoyltransferase activity in the starved state, but the Ki value for malonyl-CoA was substantially decreased by oestrogen. Treatment with a more physiological concentration of ethynyloestradiol (15 micrograms/kg body wt. per day) also produced a decrease in the Ki value for malonyl-CoA. These data suggest that the oestrogen may produce its anti-ketogenic effect by increasing the affinity of carnitine palmitoyltransferase for its physiological inhibitor, malonyl-CoA.

Acyltransferases↗
PubMed1986

Effects of high-dose ethinyl estradiol on serum concentrations and hepatic secretion of the very-low-density lipoprotein, triacylglycerol, cholesterol, and apolipoprotein A-I in the rat.

Female and male rats were treated with ethinyl estradiol (5.0 mg/kg daily for 5 days). Control animals were pair fed to compensate for the reduction in food intake induced by the estrogen, or were fed ad libitum. Treatment with ethinyl estradiol reduced total cholesterol and apolipoprotein A-I concentrations in the serum of female and male animals. The concentrations of serum and hepatic triacylglycerol were depressed markedly in animals of both sexes in groups treated with ethinyl estradiol, compared to the control group fed ad libitum. Compared to the pair-fed controls, however, ethinyl estradiol had only a very minor further reduction on serum triacylglycerol concentration. In male and female rats, the synthesis and secretion of triacylglycerol by the liver was, in comparison to the pair-fed controls, stimulated by estrogen, whereas the secretion of unesterified cholesterol was unaffected by any of the treatment regimens. The synthesis and secretion of total cholesteryl esters by livers from male and female rats was increased by treatment with ethinyl estradiol. The hepatic synthesis and secretion of VLDL triacylglycerol and cholesteryl ester was stimulated by ethinyl estradiol in male and female rats, and the VLDL particle was enriched with cholesteryl ester. Treatment with the high-dose estrogen increased the secretion of apolipoprotein A-I by livers from female rats. It is suggested that the depression in the serum concentrations of cholesteryl esters and apolipoprotein A-I is the result of increased rates of hepatic and/or peripheral catabolism of these components and that the hepatic production rates were increased or unaffected in animals administered high doses of ethinyl estradiol. Since the secretion of apolipoprotein A-I by livers from male rats was unaffected by treatment with ethinyl estradiol, the response to estrogen may be sex related.

Animals↗
PubMed1981

Alterations of plasma HDL lipids and apolipoproteins in female rats treated with ethynyl estradiol.

Female Sprague-Dawley rats (160-200 g body weight) were injected subcutaneously daily for 14 days with 1, 5, 15, 50 or 100 micrograms ethynyl estradiol in sesame oil/kg body weight, or with oil alone. Food consumption was restricted to 15 g/day, and animals were fasted overnight before exsanguination. Concentrations of plasma cholesteryl ester decreased with increasing dosage of ethynyl estradiol, as a result of decreases in HDL cholesteryl ester. Concentrations of plasma unesterified cholesterol were not altered by treatment; the tendency for a decrement in the HDL cholesterol was not statistically significant. Plasma and HDL phospholipid also tended to decrease with increasing dose of ethynyl estradiol. Plasma levels of apolipoprotein A-I increased on treatment with 5 micrograms ethynyl estradiol/kg but were diminished at a dose of 50 micrograms ethynyl estradiol/kg. The ultracentrifugally isolated high density lipoproteins were delipidated and the distribution of apolipoproteins was characterized by SDS-polyacrylamide gel electrophoresis and esoelectric focusing. The proportion of apolipoprotein E in HDL was depressed, while apolipoprotein A-I was increased and apolipoprotein C unchanged by treatment with ethynyl estradiol. Clearly, the alterations in plasma HDL lipid levels resulting from treatment with ethynyl estradiol were accompanied by distinct changes in composition of the apolipoproteins of HDL, and a biphasic response dependent on dose of the drug. A possible mechanism for the diminution in the proportion of HDL apolipoprotein E may be the enhanced removal of the apolipoprotein E-rich (HDL1) subfraction of the HDL from the circulation on treatment with ethynyl estradiol.

Animals↗
PubMed1981

Lack of effect of somatostatin on the glucagon-induced alterations of hepatic metabolism of [1-14C]oleate.

Livers from normal fed male rats were perfused in a recycling system in vitro. Glucagon was infused in varying quantities to give final concentration in the cell-free perfusate of 4.9 . 10(-10)-4.9 . 10(-7) M after 3 h of perfusion, assuming no degradation of the hormone. Where indicated, cyclic somatostatin was infused simultaneously to give a final concentration of 3.0 . 10(-6) M. In the absence of somatostatin, glucagon at a concentration as low as 4.9 . 10(-10) M increased the release of glucose and increased ketogenesis, but impaired the synthesis and release of perfusate triacylglycerol and very low density lipoprotein lipids. Somatostatin did not affect these actions of glucagon. Somatostatin alone, however, did reduce the output of very low density lipoprotein. It is suggested that the alteration of fatty acid metabolism by somatostatin in vivo results from modulation of pancreatic glucagon secretion, not from interference by somatostatin of the action of glucagon on the liver.

Animals↗
PubMed1981

Effects of diuretic and propranolol on plasma lipoprotein lipids.

Ticrynafen (TCNF), a nonthiazide diuretic, has been reported to be nonhyperlipidemic. To define the effects of these drugs on plasma lipoproteins, experiments were performed in hypertensive subjects after placebo therapy, 4 wk after therapy with either hydrochlorothiazide (HCTZ) or TCNF, 3 mo after diuretic with propranolol, and 1 mo after therapy with propranolol alone. Plasma lipoproteins were separated by ultracentrifugation and the lipid fractions isolated by extraction and silicic acid thin-layer chromatography. Plasma low-density lipoprotein (LDL) total cholesterol fell and high-density lipoprotein (HDL) total cholesterol rose in subjects receiving TCNF. TCNF had no effect on plasma low-density lipoprotein (VLDL) triglyceride or phospholipid. There was no significant changes in LDL or HDL total cholesterol in subjects on HCTZ. HCTZ tended to increase plasma VLDL triglyceride and phospholipid. The addition of propranolol to either diuretic had no effect on LDL or HDL total cholesterol but increased VLDL triglyceride, especially in subjects on HCTZ. Propranolol alone had no effect on any of the lipids measured.

Adult↗
PubMed1981

The effects of 17 beta-estradiol and progesterone on the metabolism of free fatty acid by perfused livers from normal female and ovariectomized rats.

To determine whether any interaction occurs between progesterone and 17 beta-estradiol in the regulation of FFA metabolism by the liver, normal female rats were injected sc daily for 14 days with 7.5, 15, 50, or 100 microgram 17 beta-estradiol/kg, 25 mg progesterone/kg, 15 microgram 17 beta-estradiol plus 25 mg progesterone/kg, or vehicle (sesame oil) alone. To determine the effects of these hormones in the absence of endogenous estradiol and progesterone, ovariectomized rats were treated with the steroids. Livers were removed from the variously treated rats and perfused in vitro in a recycling system. An albumin-oleate complex was infused into the perfusate, providing a steady state concentration of 0.3--0.5 nM oleate. The uptake of FFA and output of ketone bodies and glucose by the livers were generally not altered by any of the steroid treatments. Neither these parameters nor triglyceride secretion was altered by ovariectomy. The administration of 15, 50, and 100 microgram estradiol/kg to normal, but not ovariectomized rats, increased triglyceride secretion. Progesterone alone had no effect on the secretion of triglyceride, but did antagonize the estradiol-mediated stimulation of triglyceride secretion in normal rats. The molar ratios of phospholipid to triglyceride and cholesterol to triglyceride of the very low density lipoprotein secreted by livers from normal females treated with estradiol were not altered, suggesting that the livers secreted more very low density lipoprotein particles of the same size. Based on the same criteria, livers from ovariectomized rats secreted smaller very low density lipoprotein particles compared to livers from control animals, an effect which was reversed by the administration of estradiol. We conclude that progesterone antagonizes the stimulation of hepatic triglyceride secretion by estradiol in normal female rats and that ovariectomy prevents this effect of progesterone.

Animals↗
PubMed1980

Hepatic metabolism of [1-14C]oleate in pregnancy.

Livers from normal ad libitum fed nonpregnant and 20 day pregnant rats were perfused in vitro. Uptake and utilization of [1-14C]oleate were measured while the concentrations of free fatty acids in the erythrocyte-free perfusate was maintained at a steady-state level (mean 0.42 +/- 0.03 (S.E.) mM). Pregnancy increased the incorporation by the isolated liver of [1-14C]oleate into perfusate triacylglycerol and cholesteryl esters and into hepatic triacylglycerol, phospholipid, diacylglycerol and cholesteryl esters. The conversion of [1-14C]oleate by the livers into ketone bodies and CO2 was depressed by pregnancy. With pregnancy, the output of the very low density lipoprotein triacylglycerol, cholesterol, cholesteryl esters and phospholipid was increased significantly by the perfused liver. The relative molar composition of the lipid components of the very low density lipoproteins, however, was not altered by gestation, suggesting that the number of particles secreted was increased by pregnancy. The total output of glucose was decreased by livers from pregnant rats. It may be concluded from these data that livers from pregnant rats in late gestation channel fatty acid ([1-14C]oleate) preferentially into products of esterification rather than into products of oxidation.

Animals↗
PubMed1979

Effects of ethynyloestradiol on the metabolism of [1-14C]oleate by perfused livers and hepatocytes from female rats.

Normal female rats were given 15mug of ethynyloestradiol/kg body wt. for 14 days and were killed on day 15 after starvation for 12-14h. The livers were isolated and were perfused with a medium containing washed bovine erythrocytes, bovine serum albumin, glucose and [1-(14)C]oleic acid; 414mumol of oleate were infused/h during a 3h experimental period. The output of bile and the flow of perfusate/g of liver were decreased in livers from animals pretreated with ethynyloestradiol, whereas the liver weight was increased slightly. The rates of uptake and of utilization of [1-(14)C]oleate were measured when the concentration of unesterified fatty acid in the perfusate plasma was constant. The uptake of unesterified fatty acid was unaffected by pretreatment of the animal with oestrogen; however, the rate of incorporation of [1-(14)C]oleate into hepatic and perfusate triacylglycerol was stimulated, whereas the rate of conversion into ketone bodies was impaired by treatment of the rat with ethynyloestradiol. Pretreatment of the rat with ethynyloestradiol increased the output of very-low-density lipoprotein triacylglycerol, cholesterol, phospholipid and protein. The production of (14)CO(2) and the incorporation of radioactivity into phospholipid, cholesteryl ester and diacylglycerol was unaffected by treatment with the steroid. The net output of glucose by livers from oestrogen-treated rats was impaired despite the apparent increased quantities of glycogen in the liver. The overall effect of pretreatment with oestrogen on hepatic metabolism of fatty acids is the channeling of [1-(14)C]oleate into synthesis and increased output of triacylglycerol as a moiety of the very-low-density lipoprotein, whereas ketogenesis is decreased. The effect of ethynyloestradiol on the liver is apparently independent of the nutritional state of the animal from which the liver was obtained. It is pertinent that hepatocytes prepared from livers of fed rats that had been treated with ethynyloestradiol produced fewer ketone bodies and secreted more triacylglycerol than did hepatocytes prepared from control animals. In these respects, the effects of the steroid were similar in livers from fed or starved (12-14h) rats. Oestrogens may possibly inhibit hepatic oxidation of fatty acid, making more fatty acid available for the synthesis of triacylglycerol, or may stimulate the biosynthesis of triacylglycerol, or may be active on both metabolic pathways.

Animals↗