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Biomedical subjects

D R Sullivan

Publications and source records attributed to D R Sullivan.

32 records · Page 2Linked to original sources
PubMed1992

Increased oxidizability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation.

Atherosclerosis is considered to be the major complication of diabetes mellitus. Since diabetic patients have increased blood levels of lipid peroxidation products we investigated whether the susceptibility of blood components to oxidation is altered in this disease. We analysed the parameters characterizing the extent of oxidative change and the antioxidant status of low density lipoprotein (LDL) and high density lipoprotein (HDL) in a group of diabetic patients and in a control population. LDL oxidizability was significantly higher for patients (P = 0.001) than for individuals in the control group. There were no significant differences in the alpha-tocopherol content or levels of performed peroxides in LDL samples isolated from diabetic patients and control individuals which could account for this effect. Similarly, LDL glycation, common in diabetes mellitus, was not responsible, since LDL glycated in vitro was more rather than less resistant to oxidation. Even the presence of unbound glucose at normal or elevated physiological concentrations had a delaying effect on the oxidation of LDL. The increased oxidizability of LDL isolated from diabetic patients could be reduced to control levels by a 6-week standard treatment with Probucol, originally applied to reduce their blood cholesterol.

Adult↗
PubMed1991

Plasma lipoprotein distribution of apolipoprotein(a) in the fed and fasted states.

In order to quantitate the contribution of triglyceride-rich lipoprotein (TRL) apolipoprotein(a) to total plasma apo(a) concentration in the fed and fasted states, we have studied a group of 20 male subjects (age 49 +/- 3 years) with fasting apo(a) concentrations varying from 39 to 1385 U/l. After a 12-h overnight fast, each subject was given a fat-rich meal (1 g fat/kg body weight) and venous blood samples were obtained at hourly intervals for 10 h. TRL were isolated from bihourly plasma samples by ultracentrifugation (d less than 1.006 g/ml) and apo(a) was measured by radioimmunoassay. Total plasma apo(a) concentration did not change after the meal. However, TRL apo(a) increased significantly (0 h: 3 +/- 1, 4 h: 30 +/- 7 U/l; p less than 0.001) and 'd greater than 1.006' apo(a) decreased (0 h: 267 +/- 56, 4 h: 231 +/- 50 U/l; P less than 0.05). Similar postprandial changes were observed in apoB concentration (TRL apo B at 0 h: 10.3 +/- 1.5, 4 h: 13.6 +/- 1.7 g/l, P less than 0.001, 'd greater than 1.006' apoB at 0 h: 118 +/- 7, 4 h: 110 +/- 7 g/l, P less than 0.001). In the fasted state 2.0 +/- 1.0% and in the fed state (4 h postprandially) 16.0 +/- 4.6% of total plasma apo(a) was found in the TRL fraction. Eleven subjects had less than 10% of total apo(a) in TRL, 5 had 25% or more apo(a) in TRL in the fed state. Postprandial increase in TRL apo(a) was significantly correlated (r = 0.75, P less than 0.001) with increase in plasma triglycerides. TRL apo(a) concentration in the fed state was not correlated with total fasting cholesterol, triglyceride, apo(a) or HDL cholesterol concentration. We conclude that in some individuals, TRL apo(a) makes a significant contribution to total plasma apo(a) concentration in the fed state.

Adult↗
PubMed1991

Cyclosporin A blood levels are not influenced by dietary alterations in lipids.

The bioavailability of an oral dose of cyclosporin A (CSA) is variable. CSA is highly lipid soluble with approximately 40% of the CSA in the intravascular compartment bound to lipoproteins. This study was undertaken to determine what effect acute alterations in plasma lipids following a high fat meal would have on CSA whole blood levels 12 to 14 hours after the last dose. Fifteen renal transplant patients with stable renal function and on CSA therapy alone for a minimum of three months were investigated. Anthropometric data was recorded and baseline blood samples were drawn for CSA, liver function, renal function, vitamins A and E. triglycerides, cholesterol and lipoproteins following an overnight fast. The subjects then received a high fat (72.8% of caloric value) or a low fat (12% of caloric value) meal and post-prandial samples were drawn at two and four hours. The correlation between CSA levels (r = 0.72) taken on the two study days (one week apart) was less than expected despite no change in dosage. Cholesterol levels remained unchanged but triglyceride levels rose following the high fat meal. CSA levels did not correlate with the post-prandial changes in triglycerides, nor with any other parameter of lipid metabolism, lipid transport, or total body fat. This study demonstrated that CSA whole blood levels are not influenced by acute variations in lipids following a meal and therefore the time of sampling for a CSA trough level will not be influenced by the proximity to a recent meal.

Adult↗
PubMed1990

Vitamin E content and low density lipoprotein oxidizability induced by free radicals.

Human LDL, HDL and lipoprotein deficient plasma isolated from 15 normal subjects was exposed to oxygen free radicals generated by gamma rays and the formation of peroxides and changes in levels of LDL alpha-tocopherol were measured. LDL exhibited an initial resistance against oxidation stress when compared to HDL. The results obtained for different individuals showed that there was no correlation between the initial levels of vitamin E in LDL or plasma and the amount of peroxide formed after exposure of the LDL to a standard quantity of oxygen radicals. Kinetic experiments with original LDL and LDL containing incorporated alpha-tocopherol demonstrated that the vitamin performed its antioxidant role by conferring some early protection to the lipids, being consumed in the process, but it was clear that additional factors are also instrumental in determining the total antioxidant potential of the human LDL.

Adult↗
PubMed1990

The effects of dietary n - 3 fatty acid in animal models of type 1 and type 2 diabetes.

We studied the incorporation of dietary n - 3 fatty acids from marine oils into red cell membranes, using animal models of type 1 diabetes (streptozotocin-treated Wistar rats) and type 2 diabetes (gold-thioglucose-injected CBA/T6 mice). In type 1 diabetic rats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were higher following marine oil supplementation, and the increase in EPA was significantly greater than in non-diabetic animals (3.4 +/- 1.4% vs. 0.8 +/- 1.6%). Marine oil supplementation also resulted in higher levels of EPA and DHA in mice, but the increases were quantitatively similar with and without type 2 diabetes. Improvement in glycosylated haemoglobin following n - 3 fatty acid feeding was only found in type 2 diabetes (6.5 +/- 2.9% vs. 9.5 +/- 1.2%). This was associated with a higher plasma insulin concentration (170 +/- 40 vs. 136 +/- 41 mU/ml). The theory that n - 3 fatty acids improve insulin sensitivity would have predicted a decrease in plasma insulin levels. Our results suggest that n - 3 fatty acids may modify insulin secretion.

Animals↗
PubMed1990

A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors.

We developed a new angiographic score of the extent of coronary disease (extent score), which we compared with conventional stenosis and vessel scores that emphasize the severity of stenosis. Scores were determined in 132 patients (29 women, 103 men with a mean age of 55 +/- 10 years) who underwent elective coronary angiography. Risk factors were more closely related to the extent score than to either the stenosis or vessel scores (Total R2 = 0.35 versus 0.28 (p less than 0.001) and 0.25 (p less than 0.001), respectively). The extent score was more closely related to age (r = 0.30, p less than 0.05), than was either stenosis (r = 0.21 ns) or vessel score (r = 0.26, p less than 0.05). Apolipoprotein B was the strongest predictor of both extent and stenosis scores but was more closely related to the extent score (r = 0.36, p less than 0.05), even after correction for age and gender. This new angiographic score that assesses the extent of coronary disease is simple to perform and correlates better with age and lipoprotein risk factors than conventional scores do.

Adrenergic beta-Antagonists↗
PubMed1990

Boys from populations with high-carbohydrate intake have higher fasting triglyceride levels than boys from populations with high-fat intake.

Experimentally, high-carbohydrate diets have been shown to elevate triglycerides, but it has not been established whether this rise is permanent or transient. The authors approached this question by studying 719 boys from worldwide populations with marked differences in long-term carbohydrate intake. Fasting serum triglycerides, total cholesterol and high density lipoprotein (HDL) cholesterol concentrations were measured in boys aged 8 and 9 years from 12 countries--eight in Europe, three in Africa, and one in Asia. A standardized protocol was used for obtaining fasting blood and for the preparation, storage and transport of serum, and all measurements were made in one laboratory. Published values were used for the United States. Mean values for lipid levels per country were compared with the percentage of daily energy intake consumed as carbohydrate or fat, as determined by survey. Boys from populations with higher carbohydrate and lower fat intake had lower low density lipoprotein (LDL) cholesterol levels (univariate regression coefficient (+/- standard error, -0.028 +/- 0.009 mmol/liter for each percent of energy from carbohydrate; p less than 0.01, n = 13), but they also had higher fasting triglycerides (0.010 +/- 0.002 mmol/liter for each percent of energy from carbohydrate; p less than 0.01, n = 13) and lower HDL cholesterol levels (-0.022 +/- 0.003 mmol/liter for each percent of energy from carbohydrate; p less than 0.001, n = 13). These trends agree with results from epidemiologic studies within populations and from controlled dietary trials, and suggest that in normolipidemic healthy subjects, high-carbohydrate, low-fat diets cause higher triglyceride levels than diets that are higher in fats and oils.

Africa↗
PubMed1989

Elevated apolipoprotein(a) levels in cancer patients.

Elevated plasma lipoprotein(a) has been associated with an increased risk of cardiovascular disease. We report a significant elevation of total plasma apolipoprotein(a) levels in cancer patients compared with hospitalized control patients and normal healthy blood donors. Of the cancer patients studied, 48% had levels in excess of 350 mg/l compared to 20% in normal blood donors and 29% of hospitalized control patients. The elevation was more prevalent but less extreme than that reported in patients with cardiovascular disease. Density gradient centrifugation studies of plasma from cancer patients revealed the presence of apolipoprotein(a) at a density of 1.085 g/ml in the region where mRNA-containing proteolipids, neoproteolipids and malignancy-associated lipoproteins had previously been isolated.

Apolipoproteins A↗
PubMed1987

Studies of lipoproteins and fatty acids in maternal and cord blood of two racial groups in Trinidad.

The high mortality rate from coronary heart disease (CHD) among Indians compared to Negroes in Trinidad led us to test plasma lipid profiles to see whether dietary or genetic factors might be involved. There were no interracial differences in the composition of plasma cholesterol ester fatty acids of the tested women and neonates. This finding suggests that dietary fat does not account for the interracial difference in CHD, nor does the cause appear to be due to genetic differences in lipid profiles, as there was no significant difference between values for plasma triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, apo-I, apo-II, apo B or cholesterol ester fatty acids in the cord blood of each racial group. Blood samples were collected from 69 nonpregnant and 71 postpartum, fasted Negro and Indian women. Also taken were 71 umbilical cord blood samples. The mean triglyceride level was significantly lower in the Negro nonpregnant and postpartum women than in the Indians. HDL cholesterol and apo-I values were lower in the Indian women. There were no significant differences in the total cholesterol and apo B measurements. The triglyceride values for postpartum women were higher than those of the nonpregnant Negroes and Indians (75% and 47%, respectively), whereas the total cholesterol and HDL cholesterol, apo A-I and apo A-II ranged from 9% to 29% higher in the postpartum women. Apo B was about 40% higher postpartum in both ethnic groups. The high CHD rate of Indians in Trinidad cannot be explained by dietary factors, plasma total cholesterol or fatty acid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Paradoxical elevation of LDL apoprotein B levels in hypertriglyceridaemic patients and normal subjects ingesting fish oil.

Twenty-three hypertriglyceridaemic patients treated with 15 g/day of a fish oil concentrate (Maxepa) showed the expected reduction in serum triglyceride concentration but levels of LDL apoprotein B (apoB), measured by radial immunodiffusion, increased significantly. Increases in LDL apoB did not correlate with lipoprotein phenotype or changes in serum triglyceride. Studies in eight normal volunteers demonstrated that the effect of fish oil on LDL apoB was not restricted to hypertriglyceridaemic subjects. In view of the evidence that LDL apoB may be a risk factor for coronary heart disease these findings raise questions regarding the use of fish oil in the treatment of hypertriglyceridaemia.

Adult↗
PubMed1985

Determination of serum triglycerides by an accurate enzymatic method not affected by free glycerol.

In this automated single-run enzymatic procedure for specific determination of triglycerides in serum, free glycerol is removed from the reaction mixture by pre-incubation with glycerol phosphate oxidase and peroxidase. The subsequent addition of lipase and the chromogen, 4-aminoantipyrine, results in the formation of color proportional to the amount of triglycerides in serum. Standards containing triolein in aqueous detergent are used to calibrate the method. For serum pools from the Centers for Disease Control with target values of 0.74, 1.41, and 2.63 mmol/L, the method produced biases of +0.01, -0.05, and 0.00 mmol/L, respectively (mean: -0.01 mmol/L or -0.4%). The mean coefficient of variation was 1.4% within and 2.5% between days; the combined CV, 2.9%. Ninety 6-microL serum samples can be analyzed per hour. The method is more accurate and precise than one based on an NADH-coupled enzyme system with separate addition of lipase.

Ampyrone↗
PubMedDate not supplied

Triglyceride-lowering effect of marine polyunsaturates in patients with hypertriglyceridemia.

Twenty male patients with primary hypertriglyceridemia were treated for 4 weeks with daily supplements (15 g) of oil, which provided approximately 6 g of polyunsaturated fatty acid (PUFA) either of fish or of vegetable origin. Total plasma cholesterol concentrations were unaffected, but both types of supplement increased high density lipoprotein-3 (HDL3) cholesterol concentrations. The fish, but not the vegetable, oil supplement led to a decrease in plasma triglyceride concentrations. Very low density lipoprotein (VLDL), fatty acid composition, and VLDL triglyceride kinetics were subsequently studied in five patients (four male, one female) before and after 4 weeks of therapy with 15 g of the same fish oil. The fish oil led to increases in the proportion of eicosapentaenoic acid in both the VLDL triglyceride and phospholipid fractions, but the increase was greater in the latter. In contrast, the proportion of docosahexanoic acid was increased only in the VLDL triglycerides. The decrease in plasma triglyceride concentrations that occurred with fish-oil therapy was accompanied by a reduction in the absolute catabolic rate of VLDL triglyceride, implying a concomitant change in synthetic rate; the fractional catabolic rate of VLDL triglyceride was unaltered. It is suggested that polyunsaturated fatty acids of marine origin may be therapeutically useful for hypertriglyceridemia.

Adult↗