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Summary The fractional removal rate of fat emulsion injected intravenously has been measured in several groups of subjects: controls, patients with hypercholesterolaemia or hypertriglyceridaemia. The intravenous fat tolerance test was also estimated in controls before and after a short ethanol perfusion. The fractional removal rate (K 2 ) is low in patients with hypertriglyceridaemia and the results obtained suggest that the intravenous fat tolerance test provides a simple mean for an estimation of the removal of triglycerides from the blood. After a constant infusion of alcohol in healthy subjects a significant reduction of K 2 is found.

Resume Afin d'etudier les effets respectifs de l'atenolol et de la prazosine sur le profil lipidique, 60 hypertendus (diastolique: 90 a 120 mmHg; systolique: 160 a 200 mmHg) en provenance de deux centres ont ete tires au sort dans les deux groupes de traitement. Le profil lipidique, stable en periode d'observation, comportait cholesterol total, triglycerides, etude en ultracentrifugation et dosage des apoproteines A1 et B par immunonephelemetrie laser; il fut realise a J-30, J0, J90 et J180. Alors que l'effet hypotenseur etait equivalent sous prazosine, cholesterol total, LDL cholesterol, apoproteines B diminuent significativement, alors qu'HDL cholesterol et apolipoproteine A1 augmentent; les variations inverses furent observees sous atenolol. Bien que la signification clinique de ces variations reste incertaine, ce type d'effet metabolique merite d'etre pris en consideration pour evaluer le rapport risque/benefice du traitement.

The nature and amount of essential fatty acids in dietary fat play a leading part in the repartition of brain polyunsaturated fatty acids (n-3 and n-6). In order to determine precisely the respective roles of linolenic and linoleic acids in the diet on rat brain development, we used two diets in which the percentage of linolenic acid (18:3 n-3) was different. The animals were fed peanut oil (group A) or rapeseed oil (group B) during pregnancy and throughout lactation. The study of the fatty acid composition of gastric milk showed that the levels of linoleic acid (18:2 n-6) and more so linolenic acid (18:3 n-3) were much lower than in dietary fats. In group B, the 18:3 n-3 level of gastric content was about four times lower (2.4%) than in the maternal diet (8.5%) at the beginning of the suckling period and significantly increased until weaning. Analysis of the fatty acid composition of ethanolamine phosphoglycerides showed that docosapentaenoic acid delta 7-10-13-16-19 (22:5 n-3) and docosahexaenoic acid delta 4-7-10-13-16-19 (22:6 n-3) levels increased in group B in relation to group A and, on the other hand, the docosapentaenoic acid delta 4-7-10-13-16 (22:5 n-6) level decreased in group B. The sum of (n-3 + n-6) fatty acids did not change in either group B or group A. In our experimental conditions, we found no marked effect of diet composition upon conversion of linoleic acid to arachidonic acid. In summary, linolenic acid can be utilized in the brain (rather than linoleic acid) to provide long-chain polyunsaturated fatty acids and the amount of n-3 fatty acids would correlate with the desaturation activity of docosatetraenoic acid delta 7-10-13-16 (22:4 n-6) to docosapentaenoic acid delta 4-7-10-13-16 (22:5 n-6).

The metabolism of three fat emulsions (Lipiphysan, Trive 1000, Intralipid) was compared when administered by intravenous route as complete parenteral nutrition in minipigs during 14 days. With Lipiphysan. an important accumulation of glycerides appeared in liver, spleen and lung whereas the phospholipids content of those tissues was unchanged. The three fat emulsions determined an increase of linoleic acid (18:2) percentages in glycerides and phospholipids of several tissues: liver, heart, lung, spleen and kidney. Moreover, at the level of phosphatidyl-ethanolamine (PE) in liver tissue, the three fat emulsions induced a decrease of some polyunsaturated fatty acids (C20 and C22) percentages. The observed differences in the amount of liver triglycerides between the three fat emulsions seem to be related with the removal mechanisms which appear to be dependent on each fat emulsion. In fact, all tissue lipid analyses showed an increase of 18:2 percentages which agree with an uptake of the different fat emulsions used. The decrease of polyunsaturated fatty acids percentages in PE might be due to an inhibition of elongation-desaturation system or a degradation of those fatty acids.

Plasma apo B and apo A-I were determined in 477 subjects (206 males and 271 females) by laser immuno-nephelometry. Measurements of VLDL- + LDL-cholesterol, HDL-cholesterol and triglycerides were done simultaneously. VLDL- + LDL-cholesterol and apo B values were similar in males and females and increased with age. HDL-cholesterol and apo A-I values were higher in females but stable with age. Different regression curves (HDL-cholesterol vs apo A-I) were obtained in males and females and a negative correlation was found between HDL-cholesterol or apo A-I and triglycerides. Increased body weight was associated with higher values of VLDL- + LDL-cholesterol, apo B and triglycerides in both sexes but lower values of HDL-cholesterol and apo A-I essentially in males. Finally, the study provides evidence of a relationship between smoking and alcohol consumption on the one hand, and HDL-cholesterol and apo A-I on the other.

With a model of isolated rat liver perfusion, the authors study the removal kinetic of three different fat emulsions. In experiments done with Lipiphysan, triglyceride uptake by liver is linear with a rate of 30 mg/h until the 60th minute; after blockade of the reticuloendothelial system (RES), triglyceride uptake is greatly reduced. In standard experiments done with Intralipid and Trive 1000, triglyceride content of the perfusate does not vary significantly; however, the study of free fatty acids removal done before and after liberation of hepatic triglyceride lipase by heparin seems to show that Intralipid triglycerides are slightly hydrolyzed by hepatic triglyceride lipase. The particles of Lipiphysan might be capted directly by RES cells (fast removal), whereas Intralipid might be slightly hydrolyzed (slow removal); Trive 1000 removal appears to be slow and similar to Intralipid. Those results give some explanations on data obtained in vivo in minipigs and agree with a better use of Intralipid and Trive 1000 triglycerides by extrahepatic sites.

Adverse modifications of blood lipid fractions are thought to be an additional risk factor in hypertensive patients treated with some antihypertensive drugs. The purpose of this study was to compare the changes in concentrations of lipid fractions in patients treated with either the cardioselective beta blocker atenolol or the selective alpha 1 blocker prazosin. When used in approximately equipotent doses for antihypertensive effect, prazosin and atenolol demonstrated different effects on lipid metabolism. Prazosin lowered total levels of cholesterol, low-density lipoprotein cholesterol and B-apolipoproteins, but increased the levels of high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol and A1-apolipoproteins. Changes opposite to those induced by prazosin were observed during atenolol therapy.

An automated method for measurement of glycerol is presented for the determination of post-heparin plasma clearing factor. The method has been found to have advantages over previous manual methods with regard to both speed of estimation and accuracy. Clearing factor lipase activity is significantly lower in atherosclerotic subjects than in normal subjects.

The effects of alcohol on plasma lipids removal were studied in 16 control subjects by comparative measurements of turbidity and triglyceridemia. Alcolhol was administered intravenously for 3 h, either after fat meal or 2 h before artificial lipid emulsion infusion. Compared to the control study, alcohol determines a persistant elevation of induced hyperlipemia and was thought to decrease plasma lipids removal. In fact, rats epididymal fat pads lipoprotein lipase activity is decreased after alcohol intraperitoneal administration. Moreover, in man, the fractional removal constant following an intravenous fat tolerance test was slowed down after alcohol infusion. Both results agree with the decreased removal rate of fat emulsion particles and chylomicrons on account of alcohol.

Erucic acid (22:1) metabolism was studied in human and in rats. We explored, in seven subjects, the myocardial extraction of free erucic acid, 3 h after a rapeseed oil meal; we concluded that 22:1 is extracted as other fatty acids, but oleic acid (18:1). Rat tissues Jipoprotein lipase activity was measured; it appeared that heart muscle and epididymal fat pad preparation of lipoprotein lipase liberate similarly erucic acid from chylomicrons. Then, during triérucine administration in rats, we examined the fatty acid content of triglycerides from heart, kidneys and adipose tissue; we found a tremendous accumulation of 22:1 in heart muscle in comparison with kidney. This fact is related to a slow catabolism of 22:1 in myocardium; on these results, an extra-mitochondrial oxidation of 22:1 to lower fatty acids and the secundary enzymatic adaptation of heart are discussed.

A semi-automatic method is used to measure the tissue lipoprotein lipase activity. This method includes an incubation of tissue extract of lipoprotein lipase with a triglyceride emulsion, whereafter the release of free fatty acids is measured automatically. This procedure has many advantages over previous manual methods, considering time consumption and accuracy. In animals, the adipose tissue and heart lipoprotein lipase activity depends upon the nutritional state. In human adipose tissue, the activity is 15 to 20 times lower than in animals.

Experimental studies of alcohol influence on plasma lipids were performed in men and rabbits. Ethanol infusions induced hypertriglyceridemia in the plasma of normal subjects and patients with alcoholic hepatitis. No significant difference was found between the two groups of subjects. Comparative studies of triglyceride fatty acid composition obtained in the normal state and after ethanol infusion were performed in the rabbit after labelling of adipose tissue triglycerides with unusual fatty acids. The data obtained are consistant with an extra-hepatic origin of triglyceride fatty acids synthetised in the liver under ethanol influence.

To compare the effects of prazosin and atenolol on plasma lipid concentrations, 60 patients with arterial hypertension (diastolic 90 to 120 mm Hg, systolic 160 to 200 mm Hg) were allocated at random to one of two treatment groups. The lipid profile included the determination of total cholesterol and triglyceride levels by ultracentrifugation, and assays of apoproteins A1 and B by laser immunonephelometry. Determinations were performed 30 days before and on the first, 90th, and 180th days of treatment. Both drugs had similar reducing effects on blood pressure. A significant decrease in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B, and an increase in high-density lipoprotein cholesterol and apolipoprotein A1 were observed in patients receiving prazosin, whereas patients receiving atenolol exhibited opposite changes in plasma lipids. Although the clinical significance of these findings is uncertain, such metabolic effects should be taken into account when evaluating the risk/benefit ratio of antihypertensive treatments.

Repeated thrombophlebitis with pulmonary embolism in a 28-year-old female led to the discovery of a complex malformation of the inferior vena cava which required the insertion of a clip. Three years later, recurrence of phlebitis with appearance of bipolar aphthae, arthritis and a meningeal syndrome led to the diagnosis of Behçet disease. Despite various medications for this disorder and heparin or oral anticoagulant therapy, the thromboembolic disease remained active, accompany with new exacerbations of Behçet disease. Diminished plasma fibrinolytic activity was demonstrated, probably resulting from venous endothelial vascularitis, which aggravates the consequences of the preexisting vascular malformation.

A double aneurism, located in the abdominal aorta and left common iliac was found complicating a salmonella typhimurium infection which had been present for 7 months. A by-pass operation between the inaffected iliac arteries was followed by resection of the two aneurisms. Cultures taken from the walls of the aneurisms showed the presence of salmonella typhimurium. The authors stress the particular seriousness of the spontaneous evolution of such mycotic aneurisms.

The hypertriglyceridaemia of patients with haemodialysis-treated chronic renal insufficiency was characterized in respect of the apolipoproteins C of VLDL. Using Kane's method, particular attention was paid to the CII/CIII ratio of VLDL isolated by ultracentrifugation in eleven hemodialyzed patients with hypertriglyceridaemia. There was a significant decrease of this ratio compared to twenty three patients with essential hypertriglyceridaemia. A removal defect is suggested as fundamental to the pathogenesis of the hypertriglyceridaemia of renal failure since apoprotein CII acts as a specific activator of lipoprotein lipase.

Large prospective British and American studies have shown a significant increase in the relative risk of systemic arterial complications in women taking oral contraceptives. The risk increases with age and the association of other principal risk factors including cigarette smoking; the duration of oral contraception does not seem to be closely related; the incidence does not seem to have decreased since the introduction of the minipill. The synthetic oestrogens are the main causative factor; however, the role of progesterone cannot be totally excluded. The pathogenesis of arterial thrombosis, especially in coronary and cerebral territories is discussed.

Two cases of systemic necrotizing angeitis are reported because of their very unusual presenting symptom: serous otitis media responsible for bilateral deafness. After this "invasion phase", typical polyarteritis nodosa developed. Cardiac involvement, with auriculoventricular block, and cranial neuritis were observed in both cases. The few previously published identical cases are reviewed. Specific neurological and cardiac forms of P.A.N. are discussed. It is hypothesized that the cause of this immune complex-mediated disease is infectious.

Detected using a method involving gradient electrophoresis on polyacrylamide gel, the presence of a high level of an Lp(a) was demonstrated in 17% of control subjects and 39% oh hyperlipidaemic subjects explored. The difference appeared to be particularly significant in subjects with a pure hypercholesterolaemia (type IIA) or dominant hypercholesterolaemia (type IIB), which may be accounted for by the antigenic communities and related substances in the lipid composition uniting Lp(a) to LDL. The association of frank atherosclerosis with the hyperlipidaemia substantially increased the frequency of high levels of circulating Lp(a). A combined elevation of levels of Lp(a) and LDL would seem to be associated with a particular atherogenic power.

Adipose tissue lipoprotein lipase activity (LPLA) and cellularity have been studied in controls, in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects (p less than 0.02) and decreased in insulin dependent diabetic patients (p less than 0.02). Adipocyte size is larger in obese subjects, whether diabetic or not (p less than 0.05). As defined by LPLA and cell size means, the different groups are related linearly. The implications of this relationship between LPLA and adipocyte size are considered.

In normal individuals, insulin regulates lipoprotein metabolism. It increases hepatic triglycerides (TG) secretion and makes VLDL and chylomicrons post prandial removal easy by stimulating adipose tissue lipoprotein lipase (LPL). Insulin activity and cholesterol rich lipoprotein is more complicated: by its action on VLDL and chylomicrons turn-over, it influences LDL and HDL formation. It regulates cellular cholesterol pool at different levels: stimulation of LDL receptor, but also of HMG CoA reductase. Controlling LCAT, in participates in cholesterol removal by HDL. In insulin dependent diabetes, lack of adipose tissue LPL stimulation augments triglycerid-rich lipoproteins, by slowing their catabolism, resulting in a weak increase of LDL and a lowering of HDL. In non insulin dependent diabetes with hyperinsulinism, VLDL are elevated because of insulin stimulation of triglycerid hepatic production. LDL are increasing. HDL status remains discussed: HDL cholesterol is low but HDL triglycerid is high, there is no known disturbance of apo A level. In the two types of diabetes, although mechanism is different, perturbation of lipoprotein metabolism may account for the atherogenicity of this disorders.

Inhibition enzyme immunoassay was applied to human apolipoprotein B (apo-B) from plasma. The technical conditions of the assay were determined. The detection limits of the assay were 200 ng to 10 microgram/ml. Correlation coefficients obtained between enzymoassay and rocket immunoelectrophoresis on one hand and radial immunodiffusion on the other were respectively 0.84 and 0.80. The inhibition enzymoassay provides a specific and highly sensitive method for the quantitation of apo-B.

We used enzyme immunoassay to measure apolipoprotein B concentration in human plasma. Pure lipoprotein B was isolated from serum samples of fasting normolipidemic subjects by sequential preparative ultracentrifugation and coated to a polystyrene tube surface by adsorption. Human serum samples and rabbit antiserum to human apolipoprotein B were incubated with the solid-phase lipoprotein B. Soluble antigen competed with solid-phase antigen for binding to antibodies. After washing, peroxidase-labeled sheep antibodies against rabbit immunoglobulins were added, and after further washing the bound label was assayed. This provided a direct measurement of the soluble antigen. The best technical conditions for the assay were determined. The minimum detectable concentration was 1 microgram per assay. The enzyme immunoassay yielded values that compare favorably with those obtained by radial immunodiffusion (r = 0.84) and by rocket immunoelectrophoresis (r = 0.80). The assay offers several advantages over existing techniques: sensitivity, specificity, simplicity, ane non-use of radioisotopes.

Male Wistar rats were fed rapeseed oil containing high or low levels or erucic acid for 20 weeks, and changes in the fatty acid composition of cardiac mitochondrial phospholipids were studied. Treatment with rapeseed oil containing 46.2% erucic acid showed incorporation of 22:1 (5.6%) into isolated cardiolipin from heart mitochondria. After high or low (3.7%) erucic rapeseed oil feeding, linolenic acid was slightly incorporated into cardiolipin. Moreover, both of these rapeseed oils induced a significant increase of linoleate-arachidonate ratio in phosphatidylethanolamine and phosphatidylcholine. This ratio was also significantly increased in fatty acids esterified to the beta-position of these phospholipids. On the basis of such results, we have to consider the role of linolenic acid which is present at a high level in the different rapeseed oils used, as a possible inhibitor of heart microsomal enzymes involved in linoleate arachidonate conversion. Such alterations might account for mitochondrial fragility and myocardial lesions obtained in long term rapeseed oil feeding experiments.