Biomedical subjects

D R Sullivan

Publications and source records attributed to D R Sullivan.

At least 19 recordsLinked to original sources

PubMed2003

Recent trends in lipid management: raising the bar and shifting the goalposts?

The National Heart Foundation of Australia, in conjunction with the Cardiac Society of Australia and New Zealand, updated its Lipid Guidelines at the end of 2001, but on-going modification is anticipated to stay abreast of the rapid progress in this field. Research at all levels re-affirms the fundamental importance of lipid metabolism in many physiological and pathological processes. In addition, clinical trials such as the recent Heart Protection Study broaden the indications for intervention. The present review summarizes recent advances and analyzes emerging attitudes towards diagnosis and management that will influence future recommendations and practice.

Humans↗

PubMed2001

Glycoconjugate structures of parasitic protozoa.

Glycoconjugates are abundant and ubiquitious on the surface of many protozoan parasites. Their tremendous diversity has implicated their critical importance in the life cycle of these organisms. This review highlights our current knowledge of the major glycoconjugates, with particular emphasis on their structures, of representative protozoan parasites, including Leishmania, Trypanosoma, Giardia, Plasmodia, and others.

Animals↗

PubMed2001

Cardiovascular risk in the Asia-Pacific region from a nutrition and metabolic point of view: visceral obesity.

The association between abdominal obesity and an increased risk of cardiovascular disease (CVD) is now well recognized. Both problems are becoming more prevalent within the Asia-Pacific region, but there are substantial differences within and between countries. The strength of the temporal relationship between obesity and CVD in the region has led to the suggestion that obesity is the driving force behind the continuing epidemic of CVD. This raises the question as to whether there are any special aspects to the Asia-Pacific epidemic of obesity and resultant problems as a result of genetic or developmental factors. It is clear that the experience of central obesity and its cardiovascular consequences in western society cannot be directly transposed to all countries in the region. Issues such as smoking, alcohol use and inactivity may carry different implications. The Asia-Pacific region has started from low baseline prevalence of both obesity and CVD. but this implies that the potential for major problems in the future is particularly severe.

Adipose Tissue↗

PubMed2000

The effect of a lipid-lowering diet on plasma lipids and lipoproteins in mildly hypercholesterolaemic subjects: a potential role for occasional treats.

The aim of the study was to compare the effect of a lipid-lowering diet containing chocolate confectionery with an equivalent diet that is chocolate-free. In a parallel design trial, 42 free-living subjects (19 men and 23 women), aged 46.9 yr, mildly hypercholesterolemic (6.9 mmol/L) were allocated to an American Heart Association/National Cholesterol Education Program Step 1 diet that included chocolate confectionery or an identical regimen containing no chocolate. Blood samples for the analysis of plasma lipids were obtained initially, then at 6 and 12 weeks after dietary therapy. Both groups of subjects showed a trend toward a reduction in saturated fat, with those allowed chocolate reaching borderline significance (P < 0.057). Plasma cholesterol and low density lipoprotein cholesterol concentrations were significantly lower (P < 0.03) whereas plasma triacylglycerol was significantly higher (P < 0.02) in the control group compared with the chocolate group. High density lipoprotein cholesterol was reduced in both groups. Subgroup analysis on patients with the apo E3/E3 phenotype showed that the response was identical between the control and chocolate groups. The inclusion of a modest amount of chocolate confectionery did not detract from the response of a lipid-lowering diet.

Journal Article↗

PubMed1998

Cholesteryl ester transfer in hypercholesterolaemia: fasting and postprandial studies with and without pravastatin.

Subjects with hypercholesterolaemia (HC) have increased fasting cholesteryl ester transfer protein (CETP) activity and accelerated cholesteryl ester transfer (CET) from HDL to apo B-containing lipoproteins. The aim of this study was to examine the effects of postprandial lipaemia and pravastatin treatment on plasma triglycerides (TG) and CETP activity and on CET and LDL Stokes' diameter in primary HC (n = 19, total cholesterol > or =6.5, LDL-cholesterol > or =4.5, TG <4.0 mmol/l). Samples were collected fasting and 6 h after an oral fat load (0.88 g/kg body weight) after 6 weeks therapy with placebo or pravastatin 40 mg nocte according to a double-blind randomized cross-over study. Apart from significant reductions in plasma total cholesterol, LDL-cholesterol apo B and TG. pravastatin significantly reduced CETP activity in both the fasting (mean +/- SD, 37.9+/-12.2 to 32.0+/-10.3 nmol/ml plasma per h) and postprandial state (35.5+/-11.3 to 31.3+/-9.5 nmol/ml plasma per h) compared to equivalent placebo phases. CETP activity did not change during postprandial lipaemia despite a significant 45-55% increase in CET to triglyceride-rich lipoproteins (TRL) of d <1.006 g/ml. LDL Stokes' diameter was unchanged postprandially or by pravastatin. The mass of TRL was the strongest contributor to variation in CET in both fasting and postprandial plasma, accounting for at least 77% of the variance of CET. Postprandial TRL-TG was the strongest contributor to variation in fasting LDL Stokes' diameter in untreated HC (54%) whilst HDL-cholesterol was the strongest fasting contributor to variation (45%) for placebo- and pravastatin-treated HC. We conclude that pravastatin may reduce the atherogenicity of the lipoprotein profile in HC by reducing CETP activity. Furthermore, CET is strongly influenced by postprandial lipaemia which may have a cumulative effect on LDL size.

Adult↗

PubMed1997

Comparison of methods for measurement of apolipoprotein B and cholesterol in low-density lipoproteins.

We describe a new method for the direct measurement of LDL-apolipoprotein (apo) B by using a commercial kit that isolates LDL by immunoseparation. We evaluated immunoseparation of LDL for apo B and cholesterol measurement in 46 dyslipidemic patients with LDL-cholesterol (LDL-C) between 1.5 and 8.2 mmol/L, 11 of whom had plasma triglyceride (TG) concentrations >4.0 mmol/L. There was a reasonable correlation (r = 0.94, n = 40) between LDL-apo B obtained after immunoseparation and d >1.006 kg/L apo B obtained after ultracentrifugation. LDL-C by the immunoseparation method also correlated well (r = 0.98, n = 46) with the d >1.006 kg/L cholesterol after ultracentrifugation. These results show that immunoseparation can be used to determine LDL-apo B, even in hypertriglyceridemic samples. This method may provide a quick and simple alternative for the identification of hyperapobetalipoproteinemia, even when TG concentrations are high.

Apolipoproteins B↗

PubMed1996

Changes in plasma phospholipids in the presence and absence of erythrocytes 31P-NMR time-course studies.

Whole human blood and plasma were incubated at 37 degrees C and 31P-NMR spectra were acquired from aliquots of plasma dissolved in sodium cholate. The narrow resonances of phospholipids were well resolved, allowing identification and accurate quantification of the various phospholipid classes. During the course of plasma incubation, the rate of increase in 2-lysphosphatidylcholine (2-LysoPtdCho) corresponded closely to the rate of decrease in phosphatidylcholine. However, little or no change was observed in the sphingomyelin concentrations. The rate of cholesteryl ester formation in plasma was also determined using HPLC and was observed to be similar to the rate of 2-LysoPtdCho increase in plasma; this is consistent with the rate of acyl transfer from phosphatidylcholine to free cholesterol catalysed by lecithin:cholesterol acyltransferase. However, during the course of whole blood incubation, the rate of 2-LysoPtdCho increase in plasma was significantly lower than the rate of 2-LysoPtdCho production during incubation of plasma alone (31 +/- 4 micromol x 1(-1) x h(-1) and 80 +/- 8 micromol x 1(-1) x h(-1), respectively). The difference between the rates can be attributed to the action of enzymes present in blood cells including those in the erythrocytes that catalyse acylation or hydrolysis of 2-LysoPtdCho.

Chromatography, High Pressure Liquid↗

PubMed1996

Quantitative 31P nuclear magnetic resonance analysis of the phospholipids of erythrocyte membranes using detergent.

31P Nuclear magnetic resonance (NMR) spectra of human erythrocyte lysates dissolved in sodium cholate were acquired. The narrow resonances of phospholipids were mostly well resolved, allowing identification and accurate quantitative analysis of phospholipid classes of the erythrocyte membranes. The ether-linked phosphatidylethanolamine components of the erythrocyte membranes were identified, based on the removal of plasmalogens by acidolysis and of diacyl phospholipid species by degradation using phospholipase A1. It was also shown that the introduction of double bonds on the acyl chains of phosphatidylcholine shifted the 31P NMR resonances to lower frequencies. Quantitative analyses of phospholipids from the spectra were based on their apparent molar concentrations. The recoveries of phospholipids from erythrocytes were significantly higher than those using conventional extraction procedures.

Cell Extracts↗

PubMed1996

Phospholipid composition of erythrocyte membranes and plasma of mammalian blood including Australian marsupials; quantitative 31P NMR analysis using detergent.

The phospholipid classes of erythrocyte membranes and plasma from several domestic animals and marsupials were quantified by 31P NMR using detergents. Washed erythrocyte samples were thoroughly haemolysed by tip-sonication and dissolved in sodium cholate; plasma samples were dissolved in Triton X-100. The species studied were: common wombat (Vombatus ursinus), black-striped wallaby (Macropus dorsalis), bandicoot (Isoodon macrocarpus), Eastern grey kangaroo (Macropus giganteus), Tammar wallaby (Macropus eugenii), sheep (Ovis aries), goat (Capra hircus), cattle (Bos taurus), horse (Equus caballus), dog (Canus familiaris) and rabbit (Orytolagus caniculus). There were considerable species variations in the relative abundance of erythrocyte and plasma phospholipid classes. The variations may be attributed to the habitats and diets of the animals as well as to their phylogenetic differences.

Animals↗

PubMed1996

A new molecular defect in the lecithin: cholesterol acyltransferase (LCAT) gene associated with fish eye disease.

We report a new genetic defect in the lecithin:cholesterol acyltransferase (LCAT) gene associated with classical clinical and biochemical features of fish eye disease. The 63-year-old Australian female proband also suffers from non-insulin-dependent (type II) diabetes mellitus. She presented with corneal opacities, markedly reduced HDL-cholesterol (0.1 mmol/L; < 10% of normal controls), and elevated plasma triglycerides. The presence of diabetes did not explain the lipoprotein profile, which differed markedly in comparison to two female hypertriglyceridemic diabetic subjects. Cholesterol esterification in HDL-like particles was minimal but plasma cholesterol esterification was maintained due to LCAT activity in non-HDL-containing lipoprotein fractions. DNA sequence analysis of the proband's LCAT gene showed two C to T transitions resulting in the substitution of Thr123 with Ile and Tyr144 with Cys. Allele-specific PCR amplification procedures were used to confirm the presence of the mutations in this proband and to screen for additional carriers in her family. Three first degree relatives (mother, brother, son) were heterozygous for the Thr123 --> Ile mutation and her daughter had the Tyr144 --> Cys mutation. Apart from a reduction in HDL-cholesterol levels to half the normal concentration and a 20% reduction in apoA-I levels, their plasma lipids were unremarkable. The proband's son and daughter were further investigated. Both had normal cholesterol esterification rates in plasma and VLDL/LDL-depleted plasma, but reduced LCAT activity (50% that of normal). Thus, the biochemical and phenotypic expression for fish eye disease in the heterozygote subjects was similar, irrespective of the underlying LCAT mutation.

Australia↗

PubMed1995

13C NMR investigation of cholesterol esterification rate in human whole blood.

We have previously used NMR spectroscopy to measure the acyl transfer from phospholipid to cholesterol in human plasma. In the present study we investigated the processes of transfer of cholesterol and exchange of cholesteryl ester between lipoproteins during incubation of human whole blood. The rate of cholesteryl ester increase was much greater during whole blood incubation (86-118, mean = 90 mumol l-1 h-1) compared to plasma incubation (53-93, mean = 57 mumol l-1 h-1). The rate of decrease in unesterified cholesterol was identical to cholesterol ester increase during plasma incubation, but was slower during whole blood incubation, consistent with replenishment by transfer of additional unesterified cholesterol substrate from erythrocyte membranes. The analysis of lipoprotein fractions revealed an increase in cholesteryl ester content of d < 1.063 lipoproteins; the rate of increase was 47-67 with a mean of 58 mumol l-1 h-1. Although this result is comparable with that obtained by other methods, it represents the product of both CETP and beta-LCAT activity. These NMR techniques provide simple and direct assessment of aspects of reverse cholesterol transport and warrant further investigation.

Cholesterol Esters↗

PubMed1995

Effects of cholesterol on transmembrane water diffusion in human erythrocytes measured using pulsed field gradient NMR.

The effect of cholesterol on the diffusional permeability of water in suspensions of human erythrocytes was studied by means of pulsed field gradient NMR, which unlike the relaxation NMR method avoids the use of Mn2+ ions. The analysis allows the internal and external diffusion coefficients, as well as the lifetime characterizing the rate of exchange between the two regions, to be extracted from the data. The cholesterol content of the erythrocyte membranes was altered by incubating the cells with sonicated dispersions of cholesterol/dipalmitoyl phosphatidylcholine at 310 K. It was shown that decreasing the molar ratio of cholesterol to phospholipid (C/P ratio) of the membrane, from a mean value of 0.92 for normal cells (controls) to a value of 0.46, had little effect on the intracellular mean residence lifetime and the diffusional permeability. Enriching the cholesterol content of the membrane, however, had a marked effect on the exchange lifetime and the diffusional permeability. At a C/P ratio of approximately 1.5 the rate of transport was reduced approximately 3.5-fold. A further increase of the cholesterol content, to a C/P ratio of approximately 1.9, resulted in an enhancement of the rate of transport back to a normal (control) value, which was characterized by a lifetime of 8-9 ms. The combined inhibition of the water permeability by cholesterol and pCMBS for cells with C/P ratios of 1.44 and 1.54, and by pCMBS alone for cells with a control C/P ratio resulted in the same value for Pd within experimental error.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Cholesterol effects on nonelectrolyte membrane transport in human erythrocytes: NMR magnetization transfer studies.

The cholesterol content of human erythrocytes was altered by incubating them with sonicated dispersions of cholesterol/phosphatidylcholine at 37 degrees C. 31P NMR saturation transfer experiments were used to measure the rate constant for efflux of dimethyl methylphosphonate (DMMP) from the cells, and thereby gain an estimate of the permeability coefficient. It was shown that up to 39% depletion of membrane cholesterol (cholesterol/phospholipid molar ratio of 0.46) increased the efflux rate constant and permeability coefficient of DMMP 1.55- and 1.86-fold, respectively. Enrichment of the membranes with cholesterol by 45% (cholesterol/phospholipid molar ratio of 1.57) on the other hand, decreased the efflux rate constant and permeability coefficient 1.63- and 1.79-fold, respectively. It was concluded that DMMP may be used as a probe molecule to study the functional consequences of changes in the lipid composition of erythrocytes in diseases that are associated with disorders of lipid metabolism.

Cholesterol↗

PubMed1994

A 31P nuclear magnetic resonance investigation of acyl group transfer from phosphatidylcholine to yield lysophosphatidylcholine in human plasma.

31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the rate of acyl transfer from phosphatidylcholine (lecithin, PC) in whole plasma and in high density lipoprotein (HDL). Spectral deconvolution was used to resolve overlapping resonances in the 31P NMR spectra of the phospholipids. Mean values of the acyl group transfer rates from PC in plasma and HDL were 36 mumol L-1h-1 and 19 mumol L-1h-1, respectively. The reciprocal nature of the decrease in the spectral peak intensities of PC, compared to the increase in the intensities of the lysolecithin (lysoPC) peaks, suggested a substrate/product relationship consistent with the action of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for the esterification of free cholesterol in plasma. LCAT involvement was confirmed by measuring the cholesterol esterification rate based on the 13C NMR spectra obtained on lipid extracts from plasma that had been incubated at 37 degrees C. Within experimental error, the rate of lysoPC formation in plasma was shown to be equal to that of cholesteryl ester formation.

Carbon Isotopes↗

PubMed1994

Comparability of lipoprotein measurements, total:HDL cholesterol ratio and other coronary risk functions within and between laboratories in Australia.

We assessed the intralaboratory imprecision and interlaboratory comparability of lipoprotein measurements and related cardiovascular risk functions such as the total to high density lipoprotein cholesterol (TC:HDL) ratio. Analysis of 5 separate plasma pools was carried out in 4 laboratories which regularly perform lipoprotein testing. We also performed a retrospective audit on RCPA-AACB Quality Assurance Programme data from 134 laboratories participating in the Special Lipid Programme in 1991. Intralaboratory imprecision and interlaboratory comparability are reported as coefficient of variation (cv) and its 95% confidence limit. For the national data, we calculated the percentage of laboratories within specified ranges (+/- 3, 5 or 10%) about the national mean (or median) for a given level of each analyte. Intralaboratory imprecision and interlaboratory comparability amongst the 4 laboratories were close to, or within recommended limits for, TC, TG and HDL, but the interlaboratory comparability of LDL and coronary risk functions exceeded these limits. On a national level, interlaboratory comparability of TC:HDL was within +/- 5% for only 43% of laboratories, and even fewer (26%) were within this range at higher values of the ratio. We conclude that it is not possible to recommend the use of coronary risk functions at present because of sub-optimal interlaboratory comparability. Even if measures are introduced to overcome this problem, coronary risk functions may over-simplify coronary vascular disease risk in a variety of clinical situations.

Australia↗

PubMed1994

Lipoprotein (a).

Our understanding of the pathophysiological role of lipoprotein (a) in cardiovascular disease and its clinical importance has improved, but there are still gaps in our knowledge and analytical performance that hinder the appropriate management of patients. Further information about the physiological functions of lipoprotein (a), if any, and its interactions with other risk factors is required.

Arteriosclerosis↗

PubMed1993

Postprandial changes in apolipoprotein(a) concentration of triglyceride-rich lipoproteins can be reproduced by in vitro incubation: implications for underlying mechanism.

We investigated the reciprocal changes in apolipoprotein(a) concentration in the lipoprotein of d > 1.006 and the triglyceride-rich lipoprotein (TRL) fractions of plasma which occur in vivo following fat ingestion. Twenty fasting subjects were studied before and 4 h after a fat-rich meal. In 75% of cases, in vitro incubation of the postprandial (4-h) TRL with autologous fasting (0-h) lipoproteins of d > 1.006 resulted in further substantial (> 5% total) reciprocal changes in apo(a) concentration of the 2 fractions. The increase in re-isolated postprandial TRL apo(a) was 25.1% +/- 5.1% of the total apo(a), compared to the insignificant increase (0.1% +/- 0.1%) in re-isolated fasting TRL. Most of the further increase in 4-h TRL apo(a) (94% +/- 4%) could be achieved by incubation with the corresponding 4-h chylomicron fraction (CM) alone. The re-isolated 4-h TRL apo(a) concentration correlated positively with 4-h plasma TG concentration (r = 0.65, P < 0.01) and other indices of postprandial lipaemia. In vitro incubation of pooled serum lipoproteins of d > 1.006 with serial dilutions of nascent CM obtained from chylous ascitic fluid revealed that the reciprocal changes in apo(a) concentration exhibit a curvilinear relationship with the concentration of CM triglyceride which plateaued round 7 mmol/l in this instance. We conclude that the reciprocal changes in apo(a) concentration between TRL and lipoproteins of d > 1.006 which occur in the postprandial phase are quantitatively significant and largely represent a redistribution process rather than de novo synthesis because they can be reproduced by in vitro incubation.

Adult↗

PubMed1993

Effect of pravastatin and omega-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia.

This study compared the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, fish oil, and placebo on plasma lipids and lipoproteins in patients with mixed hyperlipidemia. After an initial run-in phase, 32 patients were randomized for 6 weeks to either (1) pravastatin 40 mg/d, n = 10; (2) fish oil (himega 6 g/d, equivalent to 3 g omega-3 fatty acids/d), n = 10; or (3) placebo. After single drug therapy, in the pravastatin group mean total plasma cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B fell significantly by 23% (P < .001), 30% (p < .001), and 26% (P < .01), respectively. LDL Stokes' diameter did not change. In the fish oil group mean plasma triglycerides (TG) fell 30% (P < .05), LDL Stokes' diameter increased from 25.0 to 25.9 nm (P < .05), and there was a nonsignificant increase in LDL-C. There were no changes in the placebo group. To assess the effect of the combination of pravastatin plus fish oil therapy, all patients, except one woman from the placebo group who developed nausea on fish oil, then took combined therapy of pravastatin 40 mg/d plus fish oil 6 g/d for an additional 12 weeks. In each case, there were no clinically significant episodes of muscle tenderness or elevation of creatine phosphokinase or alanine aminotransferase. After 12 weeks of combined therapy of pravastatin plus fish oil, there were significant reductions in the mean TC, TG, LDL-C, and apoB in the three groups compared with baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗