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P Janetschek

Publications and source records attributed to P Janetschek.

9 recordsLinked to original sources

Fat restriction alters the composition of apolipoprotein B-100 containing very low-density lipoproteins in humans.

We investigated effects of fat saturation and fat restriction on very low-density apolipoproteins (VLDL) including the isoforms. Normolipidemic women (22) were given a reference diet, a polyunsaturated diet, and a low-fat, polyunsaturated diet for 6 wk each. The polyunsaturated diet decreased cholesterol and apolipoprotein B levels in VLDL (-33.1% and -23.8%) and in LDL (-13.5% and -8.8%) without affecting HDL. The low-fat, polyunsaturated diet resulted in a reincrease of VLDL triglycerides, but not of VLDL cholesterol. Concentration of VLDL apolipoprotein B fell further (-41.6%). All VLDL apolipoprotein B was in the B-100 region. Though the apolipoprotein E phenotype (E-3/E-3) remained constant, a shift to more (nonsialated) apolipoprotein E isoforms could be confirmed, resulting in an increased apolipoprotein E-3 to apolipoprotein E-2 area ratio (+30.6%). This study indicates that restriction of dietary-fat intake alters the composition of apolipoprotein B-100 containing VLDL that may be favorable for atherogenesis.

Adult

Effects of diazoxide-induced reversible diabetes on chemically induced autochthonous mammary carcinomas in Sprague-Dawley rats.

The effect of oral administration of diazoxide on rats bearing mammary carcinomas induced by dimethylbenzanthracene (7,12-DMBA) or methylnitrosourea (MNU) was investigated. Administration of 300 mg/kg diazoxide caused mild reversible diabetes with maximum glucose levels of 305 +/- 74 (control: 119 +/- 12) mg/dl and related insulin levels of 15 +/- 5 (control: 24 +/- 11) microU/ml after 4 hr in tumor-bearing animals. Following the same dose of diazoxide a more than 90% inhibition of tumor growth was observed in 7,12-DMBA- and MNU-induced autochthonous rat mammary carcinomas as well as remission of the median total tumor volume per group in 7,12-DMBA-induced lesions. Frequently, onset of remissions and median remission duration proved to be dose-dependent in 7,12-DMBA-induced mammary carcinoma and, with the exception of the median remission duration, in MNU-induced tumors too. After cessation of diazoxide application, 30% rebound responses were observed in 7,12-DMBA-induced tumors of animals that had had a first remission due to diazoxide. Application of insulin (2 IU per rat) together with diazoxide (300 mg/kg) reversed the tumor-inhibiting effect of diazoxide in MNU-induced tumors. The diazoxide effect might in part be due to a decrease in the percentage of proliferating cells caused by insulin depletion as indicated by a lower amount of cells in S-phase, as measured by DNA-flow cytometry. Marked toxicity was observed after effective doses of diazoxide; the experiments indicate that induction of reversible diabetes might be a useful tool in the treatment of hormone-dependent mammary carcinoma.

9,10-Dimethyl-1,2-benzanthracene

Influence of polyunsaturated fats and fat restriction on serum lipoproteins in humans.

This study was designed to determine the effects of polyunsaturated fats and of reducing intake of total fat on serum lipids, lipoproteins, and apolipoproteins. Twenty-two normolipidemic women living in a nunnery were given a reference diet (fat/carbohydrate 42/46% of energy, P/S ratio 0.16), a polyunsaturated diet (42/46%, P/S 1,0), and a low-fat, polyunsaturated diet (32/56%, P/S 1.0) for 6 weeks each. Serum and lipoprotein lipids were determined by standard procedures, apolipoproteins either by laser immunonephelometry or by rocket immunoelectrophoresis. Consumption of the polyunsaturated diet decreased cholesterol and apolipoprotein B levels in VLDL (-33.1% and -23.8%) and in LDL (-13.5% and -8.8%) without affecting HDL. Consumption of the low-fat, polyunsaturated diet resulted in a reincrease of VLDL triglycerides, but not of VLDL cholesterol. Concentration of VLDL apolipoprotein B further fell (-41.6%) and that of apolipoprotein E decreased (-25.9%), resulting in an increased VLDL lipid/apolipoprotein mass ratio. This study indicates that responses to therapeutic polyunsaturated diet are lowered levels of VLDL and LDL, but unchanged levels of HDL. Additional restriction of dietary fat intake alters the VLDL composition with a decrement in apolipoprotein E enriched VLDL particles.

Adult

Effect of fenofibrate on serum lipoproteins in subjects with familial hypercholesterolemia and combined hyperlipidemia.

The effects on serum lipoproteins were studied in 8 patients with familial heterozygous hypercholesterolemia and 9 patients with familial combined hyperlipidemia during an 8-week treatment with fenofibrate. VLDL, IDL, LDL and HDL were isolated by ultracentrifugation and precipitation. Lipids and apolipoproteins A-I and B were determined by enzymatic and immunonephelometric techniques, respectively. In hypercholesterolemia, administration of fenofibrate resulted in decreases of VLDL, IDL, and LDL (cholesterol -58.3%, -28.6%, and -24.4%), while, in combined hyperlipidemia, treatment with the drug lowered VLDL and IDL (-33.3% and -42.9%). HDL cholesterol and apolipoprotein A-I increased only in hypercholesterolemia (+22.9% and +6.9%).

Adult

Changes in very low and low density lipoproteins with dietary fat modification.

Since VLDL and LDL are involved in atherogenesis, their response to dietary modification was studied in 15 normal male prisoners. A 3-month reference diet (P/S ratio 0.3, daily cholesterol intake 370 mg) was compared with a modified fat diet (P/S 1.0, 250 mg) given for further 3 months. The decrement in serum cholesterol by 32 mg/dl reflected a decrease in VLDL and LDL. It was associated with a decrease in serum apolipoprotein B by 16 mg/dl and in serum apolipoprotein E by 1.2 mg/dl. The decrement in VLDL cholesterol was paralleled by a lowered VLDL apolipoprotein E content. Serum and VLDL triglycerides, HDL cholesterol and the serum apolipoproteins A-I and A-II did not change significantly. One beneficial result of a conventional dietary regimen is lowered LDL with unaffected HDL. Another effect is the apparent modification of VLDL with a decrement of cholesterol and apolipoprotein E-enriched particles.

Adult

High density lipoproteins unaffected by dietary fat modification.

Since diets containing a high P/S ratio have been reported to have detrimental effects on HDL, the effect of a moderately modified fat diet (P/S ratio 1.0, cholesterol content 250 mg/day) was investigated in 30 healthy male volunteers, divided into 2 groups. They were either given a modified fat diet or an isocaloric control diet (P/S ratio 0.3, cholesterol content 370 mg/day) for 3 months each in a cross-over design. After 3 months of the polyunsaturated fat diet LDL cholesterol was significantly lowered by 19 and 13%, respectively, in both groups. This effect was already apparent after 4 weeks. Apo A-I and cholesterol in serum and the subfractions HDL2 and HDL3 remained unchanged. Consequently, the ratio LDL/HDL cholesterol was decreased by this diet. Dietary adherence was good according to the typical changes of the linoleic acid content in serum cholesteryl esters, to the dietary recalls and to the constant body weight. We conclude that a moderately modified fat diet supplied from mixed general food is acceptable for longer periods, effectively lowers LDL cholesterol, even in normolipoproteinemic subjects, and has no detrimental effects on HDL.

Adult