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Biomedical subjects

D Mathé

Publications and source records attributed to D Mathé.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

[Massive traumatic hemoptysis].

A case is reported of a patient who suffered a rupture of one lung as result of thoracic trauma. This gave rise to respiratory distress with massive haemoptysis which was initially treated with a double-lumen endotracheal tube, with separate lung ventilation, a chest drain and massive transfusion. A haemostatic pneumonectomy had to be performed because of the persisting and profuse bleeding.

Accidents, Traffic

Cholesterol metabolism in lean and obese Zucker rats: effects of portacaval anastomosis.

The effects of portacaval anastomosis (PCA) on cholesterol biodynamics of male adult (fa/fa) Zucker rats and their lean littermates were studied with an isotopic equilibrium method. Animals were fed with a sucrose-rich semi-purified diet. Obese rats were hypercholesterolemic (2.03 +/- 0.14 vs 1.06 +/- 0.7 mg/ml), had a cholesterol-enriched liver (135.3 +/- 14.5 vs 40.0 +/- 2.6 mg/liver) and accumulated cholesterol in body pools. However no difference in the rates of cholesterol absorption, synthesis, fecal elimination or transformation into bile acids distinguished obese from lean Zucker rats. In both lean and obese rats, PCA decreased cholesterolemia by about 28 per cent and liver weight by 40 per cent while the total cholesterol content of the liver was not affected. Input of synthesized cholesterol (internal secretion) was strikingly decreased by the shunt (from 13.2 +/- 0.6 and 12.6 +/- 0.7 mg/day/rat before PCA, to 8.9 +/- 0.8 and 8.6 +/- 1.0 mg/day/rat after PCA) in lean and obese rats respectively. A similar decrease was observed in the cholesterol transformation into bile acids. Since the activity of the gut for cholesterol synthesis, as shown by the fecal external secretion (cholesterol synthesized by the gut and directly eliminated in the gut and feces) was probably not modified, the reduction of internal secretion induced by PCA resulted from decreased hepatic cholesterogenesis. It is suggested that this decrease may be one of the factors involved in the lowering effect of PCA on plasma cholesterol level.

Animals