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Biomedical subjects

D Mathé

Publications and source records attributed to D Mathé.

At least 19 recordsLinked to original sources
PubMed1995

Dyslipidemia and diabetes: animal models.

Many models of diabetes dyslipidemia are available. Animals with chemically-induced diabetes have been used to study insulin-dependent diabetes. Hypercholesterolemia in streptozotocin-induced diabetes in rats results from increased intestinal absorption and synthesis of cholesterol. Lipoproteins from diabetic rats are oxidized and demonstrate cytotoxicity, a feature which can be prevented by insulin or antioxidant treatment. Diabetic rabbits fed a cholesterol-rich diet do not develop atherosclerotic lesions because accumulated VLDL are apo E-depleted, too large and do not enter into the arterial wall. Models for non-insulin-dependent diabetes (NIDDM) are obtained through selective breeding or dietary conditions. The obese Zucker rat (fa/fa) is characterized by hyperphagy, hyperglycaemia, hyperinsulinemia, insulin-resistance, hypertriglyceridemia and hypercholesteolemia. It responds to dietary, hormonal and drug treatments, but does not develop atherosclerosis spontaneously. It is used as a model for obesity, NIDDM and type IV hyperlipidemia. The JCR:LA cp rat bears the corpulent gene and develops similar characteristics to those of the Zucker rat. However, insulin-resistance is more severe in homozygous males (cp/cp), and cardiovascular lesions are observed. Their appearance is reduced by treatments which decrease hyperinsulinemia and insulin resistance but not by lowering lipid levels alone. The sand rats (Psammomys obesus) develop obesity and NIDDM when fed a laboratory diet. When cholesterol and anti-thyroid drug are added to the diet, they develop cardiovascular lesions. This species constitutes a new model for studying atherosclerosis-related diabetes.

Animals↗
PubMed1994

Effect of simvastatin treatment on plasma apolipoproteins and hepatic apolipoprotein mRNA levels in the genetically hypercholesterolemic rat (RICO).

The effects of long-term treatment with simvastatin on plasma lipoproteins, plasma apolipoproteins, and on hepatic apolipoprotein gene expression were evaluated in genetically hypercholesterolemic (RICO) rats. Simvastatin administration caused a decrease in plasma triglyceride and phospholipid concentrations. Plasma cholesterol concentration was not changed by simvastatin, but cholesterol distribution among plasma lipoproteins was altered. Plasma apo B, apo A-I, and apo A-IV concentrations were lowered by simvastatin treatment whereas plasma apo E concentration was not affected by this drug. In the liver, simvastatin treatment induced a significant decrease of apo E mRNA level but had no effect on apo B, apo A-I, and apo A-IV mRNA abundances. It appears that simvastatin may modify plasma apolipoprotein concentrations by influencing their hepatic synthesis at both pre- and posttranscriptional levels.

Animals↗
PubMed1993

Reduction of postprandial lipemia after acute exposure to high altitude hypoxia.

The effects of acute exposure to high altitude hypoxia upon plasma levels of lipids and lipoproteins were studied in 6 healthy subjects observed under strict dietary control. Fasting and postprandial values, first measured at low altitude (< 300 m), were compared to values measured 7 days after transfer by helicopter to the Observatoire Vallot (4350 m) near Mont-Blanc. Plasma levels of catecholamines and thyroid hormones were measured in parallel. Under normoxic conditions, a rise in plasma levels of cholesterol, triglycerides and phospholipids was found 4 hr after the test-meal, whereas circulating norepinephrine fell. Under hypoxic conditions, postprandial effects on lipid parameters disappeared, lipemic responses to the test-meal were dramatically reduced and plasma levels of norepinephrine increased. These effects were accompanied by a fall in triglyceride-rich lipoproteins, generally associated with a slight elevation of HDL-cholesterol, especially the less dense HDL2 fraction. When all results obtained in normoxic and hypoxic conditions were analyzed together, a series of highly significant correlations were found between the magnitude of postprandial lipidemia and various lipid parameters, in particular HDL2-cholesterol which was negatively correlated. These observations strongly suggest that high altitude hypoxia, independent of interfering variables such as exercise training or cold exposure, induced a net stimulation of the lipolysis of plasma triglycerides.

Adult↗
PubMed1993

Effects of plasma lipid levels on blood distribution and pharmacokinetics of cyclosporin A.

The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol--TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.

Adult↗
PubMed1992

Lipid and apolipoprotein changes after orthotopic liver transplantation for end-stage liver diseases.

Orthotopic liver transplantation was performed in 37 patients with different endstage liver diseases. Changes in lipid and apolipoprotein concentrations were followed daily from day 1 to 20 after surgery and regularly thereafter until 12 months. When the acute effects of surgery had cleared away, there was a sharp drop in HDL-C, apo A-I and A-II from day 1 to 5, a stabilization at their lowest values from day 5 to 15 and then a progressive rise. Contrasting with this drop, triglycerides, apo B, C-II and C-III increased from day 1 to 5 with variable concentrations thereafter. Apo SAA considerably increased early after surgery and remained significantly higher than normal in most patients after 12 months. All other parameters returned to normal from 3 to 6 months after transplant. The mechanism leading to these lipid and apolipoprotein changes are discussed with respect to the distant effect of infusions, re-alimentation, immunosuppressive therapy and lipoprotein metabolism. The apolipoprotein concentrations appear very useful indicators of functional liver recovery.

Adult↗
PubMed1991

Effect of chronic glucagon administration on lipoprotein composition in normally fed, fasted and cholesterol-fed rats.

Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 micrograms of zinc-protamine glucagon by subcutaneous injection for 8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats. Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006-1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (-57 to -81%) was observed in 1.050-1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (-70%) of fed and cholesterol-fed rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding.

Animals↗
PubMed1991

Lipolytic activities in rats fed a sucrose-rich diet supplemented with either cystine or cholesterol: relationships with lipoprotein profiles.

To study the relationships between lipolytic activities and plasma lipoprotein levels in rats, three diets were given for 8 weeks: a semipurified diet (based on sucrose, casein and lard) and this diet enriched with 5% cystine or with 1% cholesterol. Both supplemented diets induced hypercholesterolemia. Lipoprotein analysis by density gradient ultracentrifugation of plasma indicated that hypercholesterolemia of cystine-fed rats (+52%) was characterized by an increased cholesterol level in high-density lipoprotein (HDL; +131%) and low-density lipoprotein 2 (LDL2; +147%), the lipoprotein fraction containing essentially apolipoprotein-E-rich high-density lipoproteins (HDL1), and was associated with a decreased cholesterol level in triglyceride-rich lipoproteins (TRL: -69%). That obtained by cholesterol feeding (+28%) was due to a large increase in the TRL cholesterol level (+315%) whereas cholesterol was reduced in HDL (-40%) and in LDL2 (-60%). Under these dietary conditions, the activity of hepatic lipase (HL) was measured in liver homogenates and those of both HL and lipoprotein lipase were measured in plasma after heparin injection. The activity of HL (1,783 +/- 132 mU/g liver in control rats) was increased by 48% in cystine-fed rats and decreased by 40% in cholesterol-fed rats. Similar changes were observed in the activity of both lipases measured in postheparin plasma. Highly significant positive correlations linked each lipolytic activity with the level of cholesterol, phospholipids and proteins in LDL2 (HDL1-rich fraction) and in HDL. In contrast, significant negative correlations were found between all of the TRL components and the activity of the lipases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Plasma lipids, lipoproteins and apolipoproteins in two kindreds of hypobetalipoproteinemia.

Plasma lipids and apolipoproteins were quantified in two kindreds of hypobetalipoproteinemia. All affected members were asymptomatic but showed a decrease of 75% in apolipoprotein B and of 69% in LDL-cholesterol. There were no major changes in apo A-I and A-II but all affected family members had reduced levels of apo C-II (by 58%) and C-III (by 59%) without significant decrease in apo C-I and no specific decrease of apo C-III1. Apolipoprotein E is decreased in SDS-PAGE. The plasma level and phenotype of Lp(a) are not affected by HBL, suggesting that a catabolic rather than a synthetic mechanism is responsible for the disease. As shown by density gradient ultracentrifugation, HDL2 particles that contain essentially apolipoprotein A-I, cholesterol and phospholipids represent in affected subjects the major part of HDL. Due to the net reduction of apolipoprotein B-containing particles (VLDL and LDL) as acceptors of lipids in HBL, there is an accumulation of large particles rich in cholesteryl esters.

Adolescent↗
PubMed1989

Effects of chronic glucagon administration on rat lipoprotein composition.

Male adult rats of the Wistar strain received daily at 9 a.m. and 5 p.m. 10 micrograms of Zn-protamine glucagon (Novo) for 21 days by subcutaneous injections. Plasma levels of cholesterol, triacylglycerol and phospholipids were decreased by 47, 40 and 21%, respectively. Lipoproteins were separated by sequential ultracentrifugation. Concentrations of cholesterol, phospholipids and proteins were decreased in chylomicrons, VLDL, LDL2 (1.040-1.063 g/ml) and HDL, LDL2 being the most affected by glucagon treatment (-70%). Triacylglycerol levels were decreased only in chylomicrons and VLDL. The relative proportions of cholesterol, triacylglycerol, phospholipids and proteins in lipoproteins were virtually unchanged by glucagon, suggesting a reduced number of some lipoprotein particles in plasma. However, lipoproteins of glucagon-treated rats were depleted in cholesteryl esters, while the proportion of triacylglycerol increased in LDL and HDL. Apo E contents were decreased in plasma, LDL1 (1.006-1.040 g/ml), LDL2 and HDL, whereas apo B100 proportions increased in VLDL and LDL1 in glucagon-treated rats. Glucagon appeared to be a potent hypolipidemic agent affecting mainly the apo-E-rich lipoproteins.

Animals↗
PubMed1989

Efficient transformation of Bacillus thuringiensis and B. cereus via electroporation: transformation of acrystalliferous strains with a cloned delta-endotoxin gene.

Electroporation was used as a method to transform intact cells of Bacillus thuringiensis and B. cereus. With our optimized method a range of plasmid vectors could be transformed into strains of B. thuringiensis at frequencies of up to 10(7) transformants/micrograms DNA. This high frequency allows cloning experiments to be done directly in B. thuringiensis. A bifunctional vector capable of replicating in Escherichia coli and in Bacillus spp. was constructed. The kurhd1 protoxin gene was cloned into this shuttle vector to produce plasmid pX193, then transformed into B. thuringiensis HD1 cryB and B. cereus 569K. The cloned protoxin gene was expressed in sporulating cultures of both strain HD1 cryB (pX193) and 569K (pXI93), producing crystal protein active in biotests against larvae of Heliothis virescens. This demonstrates the usefulness of the electroporation method for the introduction of cloned toxin genes, in either their native or modified form, into a variety of host strains.

Bacillus cereus↗
PubMed1988

Induction of long-lasting hypercholesterolemia in the rat fed a cystine-enriched diet.

The influence of dietary excess (5%) of L-cystine on rat plasma lipoproteins was examined. After only one week of cystine feeding, an increase in the plasma cholesterol level and a decrease in triglyceride levels were observed. The increase in cholesterol level became greater when the duration of cystine-enriched diet increased until eight weeks (+131% after eight weeks), but no further increase occurred between 8 and 20 weeks. This change was essentially due to the progressive increase in cholesterol levels in high density lipoproteins (HDL) and in lipoproteins isolated between 1.040 and 1.063 g/ml, i.e., certain low density lipoproteins (LDL2), and containing mainly apoE-rich lipoproteins (HDL1). The decrease in plasma triglycerides resulted from that of chylomicrons and very low density lipoproteins (VLDL). The effects observed after four or eight weeks of cystine feeding were maintained for eight weeks after replacing the cystine diet by the standard diet. Ingestion of the standard diet containing either cholestyramine (2%) or probucol (0.25%) following eight weeks of cystine feeding significantly decreased plasma cholesterol levels. It is concluded that cystine-fed rats are a useful tool of investigation for understanding mechanisms leading to increased plasma cholesterol level and for hypocholesterolemic drug trials.

Animals↗
PubMed1987

Effect of portacaval anastomosis on plasma lipoproteins of lean and obese Zucker rats.

The distribution of cholesterol (C), triglycerides (TG), phospholipids (PL) and proteins in the different lipoproteins was studied in lean and obese Zucker rats under 2 conditions: non-operated and after portacaval anastomosis (PCA). All lipoproteins, but mainly the d less than 1.006 g/ml (chylomicrons + VLDL) fraction, were increased in obese rats. They were hypertriglyceridemic (+ 675%) and hypercholesterolemic (+ 207%). PCA decreased cholesterolemia by about 50% and triglyceridemia by 50-70% in both lean and obese rats. Except for VLDL, enriched in TG in obese rats, proportions of C, TG, PL and proteins in lipoproteins were about the same in obese and lean Zucker rats and were nearly unchanged by PCA, suggesting an increased number of particles in obese rats and a decreased number after PCA. Lipoproteins of obese rats were enriched in apo C and proportions of apo E and apo B were decreased in the d less than 1.006 g/ml fraction. PCA decreased the proportion of apo C in all lipoproteins.

Animals↗
PubMed1986

Effect of portacaval anastomosis on rat lipoproteins.

The distribution of cholesterol (C), triglycerides (TG), phospholipids (PL) and protein in the different lipoproteins was studied in male Wistar rats under 2 conditions: control and 2 months after portacaval anastomosis (PCA). PCA decreased the levels of cholesterol and the other components in chylomicrons (-90%), very low density lipoproteins (-65 to -78%), LDL2 (1.040 less than d less than 1.063 g/ml; -51 to -61%) and HDL (1.063 less than d less than 1.21 g/ml), whereas no change was observed in LDL1 (1.006 less than d less than 1.040 g/ml). Apoprotein C contents were decreased in all lipoproteins. The relative proportions of C, TG, PL and proteins in lipoproteins were essentially unchanged by the shunt, suggesting a reduced number of lipoprotein particles in plasma after PCA. It was concluded that PCA reduced the levels of all lipoproteins secreted by liver and/or the intestine without modifying those of intraplasmatic origin (LDL1).

Animals↗