Norton Spritz

Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids

Several aspects of the effects of dietary fat on plasma lipids and lipoproteins were investigated in 12 subjects during the long-term feeding of formulas containing 40% of their calories as either saturated or unsaturated fats. The changes in fatty acid composition of plasma lipids, shown previously to occur after prolonged feedings of a dietary fat, required 10-14 days to be complete and were synchronous with the effect of the fat on plasma lipid concentrations. The change in lipid concentration occurred in low but not in high density lipoproteins. The effects on lipid levels of the low density lipoproteins were found to occur with little or no effect on the concentration of the protein moiety of these lipoproteins; as a result, cholesterol- and phospholipid to protein ratios in low density lipoproteins fell during unsaturated fat feeding. The effects of dietary fat on plasma phospholipids were studied in detail: the relative amounts of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine were unaffected by the type of dietary fat. However, the molecular species of phosphatidylcholine were markedly affected. More than 90% of the fatty acids at the alpha-position were saturated during both saturated and unsaturated feedings. In contrast, during unsaturated feedings, linoleate at the beta-position outnumbered oleate by approximately 4:1, whereas during saturated feedings these two types of fatty acids were present in nearly equal amounts.This paper also presents the following hypothesis for the lipid-lowering effect of unsaturated dietary fat: since unsaturated fatty acids occupy a greater area than saturated acids, they alter the spatial configuration of the lipids into which they are incorporated; as a result, fewer lipid molecules can be accommodated by the apoprotein of the low-density lipoproteins (LDL), and thus the lipid content of the lipoprotein is lowered. The experimental findings of this study, while not proving this hypothesis, are consistent with it.

Difference in hepatic metabolism of long- and medium-chain fatty acids: the role of fatty acid chain length in the production of the alcoholic fatty liver.

Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO(2) and incorporation into esterified lipids of (14)C-labeled chylomicrons or palmitate-(14)C (representing LCFA), and of octanoate-(14)C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO(2); MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-(14)C to (14)CO(2). Furthermore, in hepatic microsomal fractions incubated with alpha-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA.

Metabolism of peripheral nerve myelin in experimental diabetes.

Previous in vitro studies of the metabolism of the peripheral nerve have been based on incorporation of radioactive precursor into components isolated from whole nerve. In this study we have determined incorporation secifically into myelin components of peripheral nerve by isolating myelin after incubating whole nerves with lipid or protein precursors and by determining the specific activity of the components of that membrane. The effect of diabetes on such incorporation was also studied. In the rat, in vitro incorporation of DL-[1-14C]leucine into protein components of myelin was decreased by 30-88% in diabetic animals as compared to controls. The major polypeptide constituent of rat sciatic nerve myelin (mol st 28,000; 58.5% of total mass of proteins) was not labeled in either the diabetic or the control group. In diabetes incorporation rate into a polypeptide of mol wt 23,000, which constitutes 21% of total mass, was approximately one half that of controls. In polypeptides of mol wt 38,000-49,000, which are heavily labeled in normal animals, but constitute only about 5% of total mass of proteins, depression of incorporation was e-en more marked in the diabetics. While these marked differences in incorporation between diabetic and control animals were observed, the amount of protein and its distribution among the constituent polypeptides was the same in both groups. In young rats made diabetic with streptozotocin and young rabbits made diabetic with alloxan, there was a lower rate of incorporation of the lipid precursors, [1-14C]sodium acetate or [3H]water, into myelin components. In older animals of both species incorporation in the controls was considerably lower than in the yount animals, and the effect of diabetes was no longer apparent. In nondiabetic animals, the in vitro addition of insulin (10-7 M) stimulated incorporation of DL-[1-14C]leucine into myelin proteins 1.6-3.1 times that of controls. This stimulation by insulin in vitro was not seen in diabetic animals. In animals in which diabetes had spontaneously recovered, however, incorporation rate in the in vitro experiments approached that of controls and were significantly above that in animals whose diabetes persisted. Since myelin is the palsma membrane of the Schwann cell, these studies provide evidence that the Schwann cell is affected by insulin and that some aspects of the metabolism of myelin are altered in insulin-deficient states.

Myelin from Human Peripheral Nerves QUANTITATIVE AND QUALITATIVE STUDIES IN TWO AGE GROUPS

Myelin in femoral nerve segments obtained at autopsy was isolated quantitatively by a series of discontinuous and continuous flotation procedures. The total amount of myelin isolated from these nerves was expressed as the sum of cholesterol, glycolipid, phospholipid, and protein and averaged 2.6+/-0.4 mg/g in a group aged 60-77 yr compared with 10.8+/-1.9 mg/g of nerve in a group aged 35-58 yr. The lower value in the older group remained apparent whether the myelin content was related to the whole nerve segment, its unit length or weight. This indicates that the decrease is an absolute one, not related to a change with aging in the nonmyelin content of nerve. No qualitative differences in myelin lipids were found between the two groups. Protein content was, however, significantly higher in the older group (34 and 28.7% of the total myelin weight, respectively). The decrease in myelin content with aging, observed by direct measurement in this study, may be the structural counterpart to age related alterations in peripheral nerve function-decreased conduction velocity, and impaired appreciation of vibration.

Hydroxy Acid Excretion in Steatorrhea of Pancreatic and Nonpancreatic Origin

Abstract Although fecal hydroxy fatty acids are known to be increased in steatorrhea, we found this increase to be inconstant in different types of steatorrhea. In eight normal subjects, hydroxy acids were undetectable in three and in no case exceeded 1.2 per cent of total fecal fatty acids. In 15 patients with steatorrhea from causes other than pancreatic insufficiency, hydroxy acid excretion per day ranged from 0.2 to 11.4 gm, representing from 5.1 to 20.9 per cent of their total fecal fat loss. In five patients with comparable steatorrhea caused by pancreatic disease, hydroxy acids were undetectable in two, were below 1 per cent of fecal fat loss in two and in the fifth amounted to 2.2 per cent of this loss. The significant difference in excretion of hydroxy acids between patients with pancreatic disease and those with other types of steatorrhea may prove diagnostically useful and suggests that only nonesterified fatty acids serve as substrate for hydroxylation by intestinal bacteria.

Decrease in Myelin Content of Rabbit Sciatic Nerve with Aging and Diabetes

Previous studies of the amount of peripheral nerve myelin have been based on histologic examination. In this study, myelin content was measured directly after quantitative isolation from sciatic nerve. There was a decrease in the amount of myelin beginning at nine months, the time of maximal myelin content in normal rabbits, and beginning at six months, the amount was decreased in diabetic as compared with control animals. Composition of myelin isolated from young (age three to four months) and old (age nine to thirteen months) rabbit sciatic nerves was also determined and is similar to that of other species. Although the composition was not affected by diabetes, with aging there was a significant decrease in the amount of cholesterol and an increase in glycolipid.

Use of a Calcium Chelating Agent(NaEDTA) in Cardiac Arrhythmias

The interrelated effects of digitalis and various cations on cardiac rhythmicity are the subject of much recent interest. This paper presents additional data on this subject that carry important therapeutic implications. The chelating agent, disodium ethylene diamine tetra acetate (NaEDTA), has been used intravenously in 14 instances of supraventricular and ventricular arrhythmia. Digitalis had been administered previously in 13 instances, and various degrees of digitalization were encountered. This report summarizes our experience with NaEDTA as a test of the degree of digitalis therapy and as treatment of the arrhythmias observed.

Decrease of ethanol-induced fatty liver by ethyl alpha-p-chlorophenoxyisobutyrate.

Summary The effect of CPIB on ethanol-induced fatty liver was studied in 7 sets of group-fed rat litter mates. Total hepatic lipids averaged 50.4 mg/g higher in the animals fed ethanol alone than in those receiving ethanol plus CPIB (p<.02) with a corresponding difference in triglyceride of 53.3 mg/g (p<.001). Hepatic total lipid and triglycerides of the CPIB-ethanol group averaged 31.3 and 30.0 mg/g higher respectively (p<.01) than the control animals fed iso-caloric diets without ethanol. These findings indicate that CPIB significantly reduces triglyceride accumulation produced by prolonged ethanol intake; in the absence of ethanol hepatic triglycerides were not decreased.

The use of L-lysine monohydrochloride in combination with mercurial diuretics in the treatment of refractory fluid retention.

Administration of large doses of L-lysine monohydrochloride at meal times has proved to be an efficient method, free of significant side effects, for the production of a hyperchloremic acidosis to restore responsiveness to mercurial diuretics in cardiac and cirrhotic patients with refractory fluid retention. Results obtained in a group of 14 patients are presented and advantages of L-lysine monohydrochloride over previously available acidifying chloride salts are discussed.

Electrocardiographic interrelationship of the pre-excitation (Wolff-Parkinson-White) syndrome and myocardial infarction

Abstract A case is presented in which electrocardiographic evidence of myocardal infarction is demonstrated in a patient with intermittent pre-excitation (Wolff-Parkinson-White) syndrome. It has been shown in this case that the QRS complex of pre-excitation phenomenon can both simulate and mask that of myocardial infarction, and that J-T segment alterations can be due to either or both when these two conditions co-exist.