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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 109 records · Page 6Linked to original sources

Uptake of fatty acids by the developing rat brain.

Polyunsaturated fatty acids are avidly taken up by the developing rat brain. To explore the specificity of this process, [1-14C]labeled 16:0, 18:2n-6, 18:3n-3, and 22:6n-3 each were co-injected with [3H]18:1n-9 into the jugular vein of two-wk-old functionally hepatectomized and sham-operated control rats. The radioactivities present in the brain, liver and serum were assessed 30 min after injection. Uptake of labeled fatty acids into brain lipids steadily increased with increasing degree of unsaturation, with more than twice as much uptake of 22:6n-3 compared to 16:0. Phosphatidylcholine was the principal radioactive species in the brain except for animals injected with [1-14C]22:6n-3, in which more of the label was incorporated into phosphatidylethanolamine. Determination of water-soluble oxidation products in the brain and serum revealed that the greater uptake of the more unsatrated fatty acids did not result from differences in rates of degradation.

Animals↗

Effects of omega-3 fatty acids in hypertriglyceridemic states.

In the experimental studies reported in this review, dietary omega-3 fatty acids from fish and fish oil had profound hypolipidemic effects in normal subjects and in hypertriglyceridemic patients with combined hyperlipidemia (type IIb) and type V hyperlipidemia. In these studies, 68 adults participated in carefully controlled metabolic experiments. In all subjects and patients, there were marked reductions in plasma cholesterol and triglyceride concentrations, with triglyceride lowering being especially great. There were also reductions in VLDL, chylomicrons, remnants, LDL, apo B, and apo E. The HDL changes were inconstant and varied from subject to subject. Whereas the mechanism of the hypolipidemic action of the omega-6-rich vegetable oils containing linoleic acid, such as corn or safflower oil, still remains obscure, the mechanism of action of the omega-3 fatty acids in fish oil has been well documented within a few years of their use as hypolipidemic agents. The synthesis of triglyceride and VLDL in the liver is greatly reduced by omega-3 fatty acids. At the same time, the turnover of VLDL in plasma is greatly shortened. LDL production is decreased. Combined with other dietary manipulations, such as a reduction in saturated fat and dietary cholesterol, the use of omega-3 fatty acids to treat hyperlipidemic and especially hypertriglyceridemic patients would appear to have a well-supported rationale. Further studies are required to delineate exact doses and precise indications for different types of hyperlipidemia and to differentiate the effects of, if any, the two major omega-3 fatty acids in fish oil, EPA and DHA. Coupled with the known antithrombotic actions of omega-3 fatty acids from fish oil because of changes in prostaglandin secretion and platelet function, these hypolipidemic effects would appear to have an important potential role in the control of coronary heart disease and other atherosclerotic disorders.

Clinical Trials as Topic↗

Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids.

Long chain n-3 fatty acids present in fish oils have been shown to reduce fasting plasma triglyceride and very low density lipoprotein levels in normal and hyperlipidemic human subjects. The present studies were designed to examine whether dietary n-3 fatty acids influence chylomicron formation and metabolism in healthy volunteers. In the first study seven subjects were fed either saturated fat, vegetable oil, or fish oil-based diets for 4 weeks each, and test meals containing 50 g of the background fat were administered after the second week of each diet. The postprandial rise in triglyceride levels was significantly lower following the fish oil test meal as compared to the saturated fat or vegetable oil test meals. In the second study, six subjects eating their usual home diets were given two fat tolerance tests. The first contained saturated fat and the second, given 1 week later, contained fish oil. There was no difference in the postprandial triglyceride response between the fish oil and the saturated fat meals. A third study was then conducted with eight volunteers in which saturated fat and fish oil test meals were administered during saturated fat and fish oil background diets in a crossover design. The presence of fish oil in the background diet reduced postprandial lipemia regardless of the type of fat in the test meal. Although there was no effect of the fish oil diet on the lipoprotein lipase and hepatic lipase activity of postheparin plasma measured in vitro, stimulation of in vivo lipolysis was not ruled out. Our results suggest that chronic (but not acute) intake of fish oil may inhibit the synthesis or secretion of chylomicrons from the gut. However, accelerated clearance due to decreased VLDL competition cannot be excluded.

Adult↗

The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina.

It is now apparent that both n-6 and n-3 fatty acids are essential for normal development in mammals, and that each has specific functions in the body. N-6 fatty acids are necessary primarily for growth, reproduction, and the maintenance of skin integrity, whereas n-3 fatty acids are involved in the development and function of the retina and cerebral cortex and perhaps other organs such as the testes. Fetal life and infancy are particularly critical for the nervous tissue development. Therefore, with respect to human nutrition, adequate amounts of omega-3 fatty acids should be provided during pregnancy, lactation and infancy, but probably throughout life. We estimate that adequate levels are provided by diets containing 6-8% kcals from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The essentiality of n-3 fatty acids resides in their presence as DHA in vital membranes of the photoreceptors of the retina and the synaptosomes and other subcellular membranes of the brain. The replacement of DHA in deficient animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the membranes for reasons as yet to be ascertained. Most significant is the lability of fatty acid composition in the retinal and brain of deficient animals. Dietary fish oil, which contains EPA and DHA, will readily lead to a change in the composition of the membrane of retina and brain, fatty acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships between the chemistry of neural and retinal membranes as affected by diet and their biological functioning provides an exciting prospect for future investigations.

Animals↗

The cholesterol/saturated-fat index: an indication of the hypercholesterolaemic and atherogenic potential of food.

A food's hypercholesterolaemic-atherogenic potential lies in its cholesterol and saturated-fat content. To help understand the contribution of these two factors a cholesterol/saturated-fat index (CSI) has been calculated. This index is based on a modification of a regression equation computed from metabolic studies designed to lower plasma lipids. A low CSI indicates low saturated fat and cholesterol content and low atherogenicity. The CSI may be used to compare different foods and recipes and to evaluate daily intake quickly and easily.

Arteriosclerosis↗

Hepatic and dermatologic manifestations of chronic hypervitaminosis A in adults. Report of two cases.

Chronic hypervitaminosis A in adults is a clinical syndrome that can develop over varying periods of time depending on the average daily intake of vitamin A. Two adult cases of chronic hypervitaminosis A are described and illustrate this diverse dosage-duration relationship. Hepatic cirrhosis developed as a manifestation of vitamin A toxicity in one of the patients; this appears to be the first reported case of chronic hypervitaminosis A in an adult induced by the long-term frequent ingestion of beef liver.

Adult↗

Absorption of cholesterol and beta-sitosterol from cigarette smoke in Macaca mulatta.

When smoke from single cigarettes containing [4-14C]cholesterol or beta-[4-14C]sitosterol was delivered to the lungs of Rhesus macaques, plasma contained radiolabeled sterols up to 50 days later. Since cholesterol, as well as plant sterols (campesterol, stigmasterol and beta-sitosterol), are normally present in cigarette smoke, our observations suggest that protracted absorption of sterols occurs after cigarette smoking.

Animals↗

Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys.

Docosahexaenoic acid [22:6 omega 3; 22:6-(4,7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other omega 3 fatty acids, chiefly alpha-linolenic acid (18:3 omega 3). We tested the effect of dietary omega 3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurified diets very low in 18:3 omega 3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3 omega 3. In near-term fetuses and newborn infants of the deficient group, the 22:6 omega 3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6 omega 3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6 omega 3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain omega 6 fatty acids, particularly 22:5 omega 6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary omega 3 fatty acids are retina and brain.

Animals↗

Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.

Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed. In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans. Compared with control subjects (n = 8), the sitosterolemic subject had an increased absorption of 22-dehydrocholesterol (71.5% vs. 43.8 +/- 11.4%, mean +/- SD), C-26 sterol (80.6% vs. 49.3 +/- 11.4%), brassicasterol (51.8% vs. 4.8 +/- 4.2%), and 24-methylene cholesterol (60.5% vs. 16.0 +/- 8.3%). This enhanced absorption was associated with an increased plasma total shellfish sterol level (13.1 mg/dl vs. 1.9 +/- 0.7 mg/dl in normals). In the sitosterolemic subject, as in normals, the shellfish sterols were not preferentially concentrated in any lipoprotein class, and 50-65% of these sterols were in the esterified form in plasma. Bile acids and neutral sterols were quantitated in bile obtained by duodenal aspiration. The bile acid composition did not differ significantly in the sitosterolemic subject compared with the normal controls. The sitosterolemic subject, though, was unable to concentrate normally the neutral shellfish sterols in bile. The normal controls concentrated the shellfish sterols in bile 6.3 +/- 1.7-fold relative to the plasma shellfish sterol concentration whereas the study subject was only able to concentrate them 2.1-fold. We propose that sitosterolemia and xanthomatosis occur from a generalized abnormality in the usual ability of the gut mucosa and other tissues of the body to discriminate among many different sterols. This has important implications for the understanding of the pathophysiology of this disease and for therapeutic recommendations.

Adult↗

Reduced prostacyclin survival after fasting-induced elevation of plasma free fatty acids.

The anti-thrombotic effect of prostacyclin (PGI2) may be determined not only by its synthetic rate but also by its subsequent survival in blood. After its release from the vascular wall, prostacyclin binds to plasma albumin which stabilizes the molecule and prolongs its inhibitory effects on platelets. In vitro studies have shown that free fatty acids compete for the same albumin binding sites and may therefore displace PGI2 and substantially shorten its survival. To see if this competition could also occur in vivo, we produced a three-fold rise of plasma free fatty acid concentrations in ten normal volunteers by four days of fasting, which led to a significant reduction in prostacyclin survival as measured by a functional assay based on inhibition of ADP-induced platelet aggregation. The shortening of prostacyclin survival was associated with evidence of increased platelet reactivity as measured by the circulating platelet aggregate ratio test. Diseases that produce marked elevations of free fatty acids such as acute myocardial infarction may also lead to shortened PGI2 survival with potentiation of platelet mediated thrombosis.

Adult↗

Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia.

Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in normolipidemic subjects. We examined the effects of fish oil in 20 hypertriglyceridemic patients: 10 with Type IIb hyperlipidemia and 10 with Type V. These patients were put on three diets differing primarily in fatty acid composition and fat content. The control diet contained a fatty acid mixture typical of a low-fat therapeutic diet (ratio of polyunsaturated to saturated fat, 1.4), the fish-oil diet contained omega-3 fatty acids, and the vegetable-oil diet was rich in the omega-6 fatty acid, linoleic acid. Each diet was followed for four weeks. In the Type IIb group, the fish-oil diet led to decreases in both plasma cholesterol (-27 per cent) and triglyceride (-64 per cent), as compared with the control diet. Very-low-density lipoproteins (VLDLs) were also reduced markedly. The vegetable-oil diet had much less effect. With fish oil, the Type V group had marked decreases in total cholesterol and triglyceride levels (-45 and -79 per cent, respectively). VLDL levels were dramatically lowered, as were apoprotein E levels. The vegetable-oil diet (unlike the fish-oil diet) produced a rapid and significant rise in plasma triglyceride levels. We conclude that fish oils and fish may be useful components of diets for the treatment of hypertriglyceridemia.

Adult↗

The effects of a high-carbohydrate low-fat cholesterol-restricted diet on plasma lipid, lipoprotein, and apoprotein concentrations in insulin-dependent (type I) diabetes mellitus.

Six women with well-defined insulin-dependent diabetes mellitus (IDDM) were studied for 4 weeks during a control diet containing 45% of the calories as carbohydrate, 40% fat (P/S ratio 0.14), 15% protein, and 580 mg of cholesterol, and for 6 weeks during a high-carbohydrate low-fat cholesterol-restricted diet with 65% carbohydrate, 20% fat (P/S ratio 1.40), 15% protein, and 62 mg cholesterol. All subjects completed both dietary periods in a crossover experimental design. Individual menus were subject-selected from a calculated exchange list containing conventional food items consistent with current American dietary patterns. The diets were well-tolerated by all subjects. Total plasma cholesterol decreased from 201 to 156 mg/100 mL (P less than 0.05) during the cholesterol-restricted diet, while total plasma triglyceride (TG) increased from 96 to 115 mg/100 mL (P less than 0.01). During this same period, very low-density lipoprotein cholesterol (VLDL-C) and VLDL-TG increased from 17 to 21 mg/100 mL (P less than 0.05) and from 59 to 76 mg/100 mL (P less than 0.001), respectively, while low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) decreased from 126 to 90 mg/100 mL (P less than 0.05) and from 50 to 39 mg/100 mL (P less than 0.05), respectively. LDL-C/HDL-C and total-C/HDL-C ratios were lower but not significantly different, and LDL-TG and HDL-TG were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Co-occurrent use of cigarettes, alcohol, and coffee in healthy, community-living men and women.

Previous studies have examined intra-individual aggregation in the use of cigarettes, alcohol, and coffee by examining the co-occurrent use of any pair of these three substances. A recent literature review failed to find a single investigation that studied use of all three in the same sample. In the present study, co-occurrent use of all three of these substances was examined in crossvalidated subsamples of 226 male and 245 female healthy, community-living, middle-class Americans. A log-linear analysis was used to compare the proportion of smokers, ex-smokers, and nonsmokers categorized as users of more or less amounts of coffee and alcohol. Although most of the intercorrelations were not strong, the results indicate that for both sexes, smokers and ex-smokers were more likely than nonsmokers to drink greater amounts of alcohol and coffee. Furthermore, for smokers, ex-smokers, and nonsmokers, a majority of individuals who reported drinking more alcohol also reported drinking more coffee. Interestingly, the coffee and alcohol consumption levels of ex-smokers resembled those of smokers more than those of nonsmokers. Also, ex-smokers reported drinking more wine and decaffeinated coffee than either smokers or nonsmokers. Finally, the number of cigarettes smoked per day (daily quantity) was positively related to total alcohol and coffee consumption in men, but not in women. Further studies are recommended to examine the role of individual differences in the development, maintenance, and modification of these three appetitive habits and their co-occurrence.

Adolescent↗

The effects of subject-selected high carbohydrate, low fat diets on glycemic control in insulin dependent diabetes mellitus.

In the present study, six women with insulin dependent diabetes mellitus (IDDM) were assigned to begin either a control diet containing 45% of the calories as carbohydrate, 40% fat, and 15% protein for four weeks, or a high carbohydrate, low fat diet with 65% carbohydrate, 20% fat, and 15% protein for six weeks. All subjects completed both periods in a cross-over experimental design. Individual menus varied, and were subject-selected from a calculated exchange list consisting of conventional food items. Subjects selected an equal distribution of carbohydrate from simple and complex sources during both dietary periods, and dietary fiber intake was only modestly greater during the high carbohydrate diet (50 g) than in the control diet period (28 g). No significant changes occurred in any measures of glycemic control between the control and high carbohydrates diets; fasting serum glucose 215 vs 213 mg/100 ml; preprandial serum glucose 214 vs 200 mg/100 ml; 24 hour urine glucose 36 vs 31 g/day; and glycosylated hemoglobin 10.3 vs 10.5% Hb A1, respectively. Similarly, insulin dose was unchanged during the control (38 IU/day) and experimental (38 IU/day) periods. These findings indicate that the application of present dietary recommendations to persons with IDDM in a realistic clinical setting led to neither an improvement nor a deterioration of glycemic control.

Adult↗

The absorption of cholesterol and the sterol balance in the Tarahumara Indians of Mexico fed cholesterol-free and high cholesterol diets.

The Tarahumara Indians of Mexico are habituated to a very low cholesterol, low fat diet and have lifelong low plasma cholesterol concentrations. To study cholesterol metabolism in these unusual people, 8 Tarahumara men were fed sequentially a cholesterol-free diet and then a diet containing 900 mg cholesterol under controlled conditions. The intestinal absorption of cholesterol, fecal steroid excretion and sterol balance were determined. During the high cholesterol diet period, the plasma cholesterol level increased from 113 +/- 8 mg/dl to 147 +/- 11 mg/dl (means +/- SD). Cholesterol biosynthesis decreased from 14.0 +/- 0.7 to 7.1 +/- 1.0 mg/kg/day (means +/- SE). The intestinal absorption of cholesterol was 27.7 +/- 6.7% (means +/- SE) during both dietary periods. Compared to other cultures, Tarahumaras had a reduced ability to absorb dietary cholesterol and higher total sterol turnover primarily because of an increased bile acid output. The total sterol disposition over three weeks of the high cholesterol diet accounted for all the absorbed dietary cholesterol.

Adult↗