The Program on the Surgical Control of the Hyperlipidemias: a status report.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.

Swine in atherosclerosis research--Development of an experimental animal model and study of the effect of dietary fats on cholesterol metabolism.

The effect of saturated (beef tallow) and polyunsaturated (corn oil) fat diets on plasma cholesterol, bile flow and composition, and excretion of fecal steroids, was studied in 5 female and 6 male miniature swine. The animals were fitted with a modified Baldwin T-tube in the common bile duct for bile sampling and a catheter in the duodenum for reinfusion. Plasma cholesterol levels were increased by beef tallow and decreased by corn oil. Both fats caused an increase in the secretion of bile, biliary lipids and bile acid pool size. The increases were significant when the source of fat was corn oil. The fecal neutral steroid excretion measured in the male swine was increased by both fats. However, only the polyunsaturated fat diet caused a significant increase in the fecal acidic steroid excretion.

The generation of phospholipase A and hemolytic fatty acids by autolysing suspensions of Trypanosoma congolense.

When T. congolense undergoes autolysis there is a concomitant appearance of phospholipase A activity and hemolytic fatty acids. The generation of enzyme activity is exponential, and the appearance of hemolytic activity corresponds to a free fatty acid concentration of 0.02 to 0.03 mg. per ml. The concentration of the trypanosome suspension markedly affected the kinetics of the generation process. In contrast, the autolysis of T. lewisi did not generate hemolytic activity unless exogenous phospholipase A was added to the organisms.

Mechanisms of the anemia in trypanosomiasis: studies on the role of the hemolytic fatty acids derived from Trypanosoma congolense.

Trypanosoma congolense releases a number of hemolytic free fatty acids on autolysis of which the most potent is linoleic acid. These fatty acids can lyse washed rat and bovine erythrocytes in vitro. Autolysed T. congoleuse will cause increased fragility of erythrocytes in whole rat blood but not in whole bovine blood. The lack of effect of these fatty acids on bovine erythrocytes tends to be confirmed by the failure of this material to influence the survival of these cells in vivo. Calculations based on the amount of free fatty acids required to cause hemolysis in vivo also confirm that this mechanism of erythrocyte destruction is probably unimportant in bovine trypanosomiasis.

The generation and identification of the hemolysin of Trypanosoma congolense.

The hemolytic activity of Trypanosoma congolense appears to be due to the presence of free fatty acids generated by the action of phospholipase A on endogenous phosphatidyl choline. Some lysolecithin also contributes to the lytic activity. Trypanosoma lewisi, being devoid of phospholipase A, does not generate free fatty acids and is therefore non-hemolytic.

The release of soluble vasoactive material from Trypanosoma congolense in intraperitoneal diffusion chambers.

Millipore diffusion chambers containing living or lysed Trypanosoma congolense cause a local inflammatory reaction when implanted intraperitoneally into rats. Empty chambers do not do this. The active material is of low molecular weight and is possibly peptide in nature. It appears to act by increasing local vascular permeability. It was found to be neither chemotactic nor cytotoxic in several assay systems. It is considered that this material may contribute to the pathogenesis of T. congolense infection in animals.

The generation of toxic activity from trypanosoma congolense.

Trypanosoma congolense organism, on incubation at 20 degrees C for 91/2h, were found to generate phospholipase like activity which was capable of mediating lysis of both nucleated cells and erythrocytes as well as acute inflammatory response on intradermal inoculation.

The dendritic cells of the guinea pig popliteal lymph node: identification and classification of cells observed by scanning electron microscopy.

Scanning electrom microscopy of guinea pig popliteal lymph nodes revealed that 3 types of cells adhered to glass and possessed extensive cytoplasmic processes. Two of these types were considered to represent extremes of a macrophage population on the basis of possession of surface receptors for cytophilic Abs, complement and immunoglobulin, as well as their distribution, quantity and morphology. The third cell type was characterized by possession of large numbers of filamentous dendritic processes. On the basis of morphology, quantity, distribution and the absence of receptors, this cell was considered to represent a cell type clearly distinct from the other cells observed in the normal lymph node.

Glucose metabolism in thyroidectomized and normal dogs during rest and acute cold exposure.

Uniformly labeled (14C)glucose was infused iv at a constant rate into unanesthetized surgically thyroidectomized (THY) and normal dogs during the basal state at 22 degrees C and during cold exposure at 4-5 degrees C. 02 uptake, CO2 output, and plasma glucose levels were determined; from these rates of glucose turnover and oxidation were calculated. Comparison of THY with normal dogs shows that at a mean plasma glucose level of 103 mg/100 ml, a significantly lower glucose turnover rate was observed in THY dogs on the basis of a kg body weight, body surface area (m-2), but not per cal BMR. The same percentage of glucose turnover was immediately oxidized in THY and normal dogs, accounting for 16 and 15% of the total caloric expenditure, respectively. Acute cold exposure increased energy expenditure in both THY and normal dogs without a change in glucose level or turnover rate. However, the percentage of glucose turnover which was immediately oxidized as well as the amount of glucose oxidized increased significantly and proportionally to the increase in energy expenditure so that the percent of calories derived from plasma glucose oxidation remained the same as that observed during the control period.

Free fatty acid and glucose metabolism during increased energy expenditure and after training.

The amount of fat available as substrate to provide the energy needed for submaximal exercise is almost unlimited; therefore, it stands to reason that the organism will adapt so that it uses fat as the major energy substrate during very prolonged exercise. Nevertheless, the quantitatively smaller body stores of carbohydrate, which contain only one to two percent as many calories as the fat stores, play a very important role during exercise, since depletion of either muscle or liver glycogen will force an individual to terminate strenuous muscular work. In normal dogs during long-lasting exercise, at energy expenditures ranging from the resting state of 0.73 kcal/m2 min to a work load of 4.66 kcal/m2 min, the FFA mobilization, and participation of FFA oxidation in total energy expenditure increases. During prolonged exercise in trained dogs, 50-90% of the energy may derive from plasma FFA, while plasma glucose contributes not more than 10% to the energy expenditure. However, there is an inverse relationship between the amount of glycogen stored inside the muscle, its rate of depletion, and muscular endurance during prolonged strenuous work. Oxidation of FFA spares muscle glycogen and in this way increases work endurance.

Glycerol turnover and oxidation in man.

The oxidation and turnover of plasma glycerol has been studied in lean and obese, fed and starving man by means of a long-term infusion of glycerol-(14)C, and the participation of glycerol in gluconeogenesis has been determined. Under none of the experimental conditions did glycerol contribute more than 10% of the total respiratory CO(2). Glycerol turnover in fed lean subjects was 106 mmoles/min. Glycerol levels and turnover were higher in the obese subjects and with all subjects after starvation. There was a direct correlation between plasma levels and turnover values for which a regression equation was derived: y = 1556 x + 33.1, when y = turnover in micromoles per minute and x = glycerol level in micromoles per milliliter. Whereas a direct relation was established between glycerol and FFA levels, the FFA/glycerol turnover ratio was 4.7:1 in the lean group indicating incomplete hydrolysis of adipose tissue triglycerides.During starvation plasma glycerol is nearly or completely converted to glucose in the lean and obese groups, respectively. Of the new glucose formed from protein and glycerol 38% is derived from glycerol in the lean and 79% in the obese. Protein and glycerol have been shown to be adequate as precursors to supply at least as much glucose as is being oxidized per day.