Approaches to lipid and lipoprotein analysis.
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Apolipoproteins↗
Biomedical subjects
M F Laker
Publications and source records attributed to M F Laker.
Elevated sodium-lithium countertransport: a familial marker of hyperlipidaemia and hypertension?
Erythrocyte sodium-lithium countertransport was measured in normolipidaemic and hyperlipidaemic hypertensive patients, hyperlipidaemic normotensive patients and normal controls. Hypertension and hyperlipidaemia were each independently associated with raised sodium-lithium countertransport (by analysis of variance, P less than 0.01 and P less than 0.01). The effects were additive so that hyperlipidaemia could not explain raised sodium-lithium countertransport in hypertension. In hyperlipidaemic hypertensive patients, levels of plasma cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol were increased, and high-density lipoprotein (HDL) cholesterol was reduced. Of these patients, 73.3% had a known family history of hypertension. Their normotensive first degree relatives were studied, and 48% of these also had raised sodium-lithium countertransport and abnormal plasma lipids (raised cholesterol, triglycerides and LDL cholesterol, and reduced HDL cholesterol). Relatives with normal sodium-lithium countertransport had normal lipids. Therefore, raised sodium-lithium countertransport was associated with the inheritance of both hypertension and hyperlipidaemia, and this could explain why raised sodium-lithium countertransport has been associated with a family history of both hypertension and associated cardiovascular disease.
Antiporters↗
The effect of pharmacological modification of gastric emptying and mouth-to-caecum transit time on the absorption of sugar probe marker molecules of intestinal permeability in normal man.
The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32-44 years, received saline, 600 micrograms atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3-O-methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l-1 and the dose administered was 80 ml m-2 body surface area. Gastric emptying was measured by ultrasound, mouth-to-caecum transit time by breath hydrogen analysis and sugar concentrations by gas-liquid chromatography. Gastric emptying half-times (min) were [mean (95% confidence intervals)] 14.9 (11:4-18.5) after saline, 22 (18.7-25.2) after atropine and 10.3 (7.0-12.6) after metoclopramide (P less than 0.002). Transit times (min) were 68.9 (52-85.2) after saline, 143 (126-159) after atropine and 38 (21.2-54.5) after metoclopramide; P less than 0.0001. Analysis of plasma levels of mannitol and 3-O-methyl glucose showed a significant within-subject effect of drug with time (P less than 0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974-1620) mg after saline, 1560 (1210-2013) mg after atropine and 955 (740-1232) mg after metoclopramide (P less than 0.03). There were no significant differences in lactulose and 3-O-methyl glucose urinary excretion between drug treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Ascorbate-induced hyperoxalaemia has no significant effect on lactate generation or erythrocyte 2,3,diphosphoglycerate in dialysis patients.
To examine the possible effects of hyperoxalaemia on anaerobic metabolism and erythrocyte pyruvate kinase activity, we induced a rise in plasma oxalate in 11 dialysis patients by the oral administration of ascorbic acid, 500 mg day-1 for 3 weeks. Blood samples were taken from the same antecubital vein before and after the supplementation period, without venous stasis, after an overnight fast. This protocol allowed patients to be used as their own controls. Five healthy subjects underwent an identical protocol to exclude any effect of ascorbate per se. Mean (SEM) plasma oxalate (mumol l-1) rose from 30.3 (3.5) to 48.4 (6.1) in patients and from 1.4 (0.2) to 6.8 (0.9) in healthy subjects. Whole blood ascorbate (mg l-1) rose from 7.0 (0.7) to 26.6 (2.5) in patients and from 9.3 (1.2) to 17.8 (1.8) in healthy subjects (reference range 7.5-20.0 mg l-1). No changes were observed in either group in plasma creatinine, bicarbonate, haemoglobin, or erythrocyte 2,3,diphosphoglycerate (2,3 DPG) after the 3 week supplementation period. Before supplementation lactate generation (area under curve, mmol min l-1) in the 5 min following a 60 s period of standardized ischaemic forearm exercise was significantly (P = 0.026) greater in patients [69.1 (4.7)] than in healthy subjects [46.9 (6.7)]; no significant change in lactate generation occurred in either group after ascorbate-induced hyperoxalaemia. We conclude that changes in plasma oxalate of the order of 20 mumol l-1 have no significant effect on lactate generation or 2,3,DPG levels in uraemic subjects.
2,3-Diphosphoglycerate↗
Drug therapy for diabetic dyslipoproteinaemia: a practical approach.
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Adult↗
Fatty acid composition of clinically healthy and malignant oral epithelium.
The fatty acid composition of epithelium from clinically healthy oral mucosa and or oral squamous cell carcinoma was analyzed by gas/liquid chromatography following extraction using a modified Folch technique and conversion of fatty acids to methyl esters. There were significant reductions in the relative proportions of palmitoleic and oleic acids and elevation of the relative proportions of palmitic, steric and arachidonic acids in samples from squamous cell carcinoma. These differences could reflect changes in cell membranes and/or fatty acid metabolism. Further studies are required to assess their functional, diagnostic and prognostic significance.
Aged↗
A case of cerebrotendinous xanthomatosis. II: The sterol content of a cataractous lens.
The cholestanol content of a cataractous lens nucleus from a patient with cerebrotendinous xanthomatosis (CTX) was quantified by gas chromatography-mass spectrometry and found to be 0.27 micrograms per mg freeze-dried lens tissue. The cholestanol-cholesterol ratio of 1.7% in the lens nucleus was similar to that in the serum of the CTX patient. The cholestanol content and cholestanol-cholesterol ratio in the CTX lens were approximately four-fold and six-fold greater respectively than the mean levels found in three senile cataractous lens nuclei analysed simultaneously for comparative purposes.
Adult↗
Effect of hyperoxalaemia on factor VIII-related antigen in uremia.
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Adult↗
A clinical application of iodine quantitation using digital fluorography.
A preliminary clinical study of 20 patients is described in which a method of iodine quantitation in vitro using digital fluoroscopy was applied to the intravenous urogram. It was possible to quantitate iodine levels, in terms of mass thickness, in both the renal parenchyma and collecting system in 38 of 40 kidneys studied (20 patients). In the two kidneys on which measurements could not be made, the cause of failure was subtraction artefact due to movement of bowel gas, compounded in one case by poor renal opacification. The variations of iodine mass thickness against time were plotted and their forms were similar to dynamic computed tomography and magnetic resonance imaging studies of transplanted kidneys. Potential clinical applications of this method, in particular the functional assessment of the dilated upper urinary tract, are suggested based on its ability to offer quantitative information in addition to anatomical images.
Adult↗
Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM.
The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM.
Bezafibrate↗
Effect of bezafibrate on metabolic profiles in non-insulin-dependent diabetes mellitus.
Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia secondary to increased hepatic glucose output and impaired extrahepatic insulin sensitivity. Many NIDDM patients also have raised serum triglyceride and low-density lipoprotein (LDL) cholesterol levels, which may require drug therapy, as well as increased plasma nonesterified fatty acid concentrations. Some hypolipidemic agents such as bezafibrate lower fatty acid levels as well as LDL cholesterol and triglycerides. It has been suggested that raised fatty acid levels may be responsible in part for the increased hepatic glucose output and insulin insensitivity of NIDDM. Several groups have therefore sought to examine the effects of fibrates on glycemic control in NIDDM. In our own studies, we used bezafibrate (200 mg t.i.d.) in a double-blind, placebo-controlled design for 3 months. Fasting blood glucose, serum insulin, C-peptide, plasma nonesterified fatty acids, blood lactate and alanine, serum triglycerides, and LDL cholesterol were all lowered. HbA1 showed no significant change. Meal hormone and metabolite profiles were all improved although this reflected mainly the lower premeal values. The results of our and other studies are sufficiently encouraging to suggest that bezafibrate could provide alternative first-line drug therapy in hyperlipidemic NIDDM patients when diet alone has failed.
Bezafibrate↗
Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability.
The lactulose/mannitol dual sugar absorption test is a non-invasive test of intestinal permeability. Its widespread use has been limited by the difficulties of analysis for carbohydrates in urine at low concentrations. We describe a "high-pressure" liquid-chromatographic method for determining lactulose and mannitol in urine, in which anion-exchange chromatography and pulsed amperometric detection are used. Sample preparation is simple and fast, and lactulose and mannitol and the internal standards arabinose and cellobiose are well resolved within 15 min. Analytical response of the method is linear with concentrations to 3 g/L, and one can detect as little as 0.3 mg of lactulose per liter of urine. Analytical recovery was between 90% and 107% for all sugars analyzed, and there was good agreement with results by a gas-chromatographic method (r = 0.993 lactulose, 0.984 mannitol). The method may potentially be applied to the study of other carbohydrates present in biological fluids at low concentrations.
Arabinose↗
Capillary column gas chromatography-mass spectrometry for the determination of the fatty acid composition of human adipose tissue.
A procedure for determining the fatty acid composition of human adipose tissue using gas chromatography-mass spectrometry was developed. Adipose tissue was obtained from the lateral upper aspect of the right thigh by needle biopsy and prepared for analysis by lyophilisation, total lipid extraction and base-catalysed transesterification of the complexed fatty acids to form fatty acid methyl esters. Capillary column gas chromatography resolved thirty different peaks, ranging in carbon length from 12 to 24. Provisional identification of the peaks was by cochromatography with authentic standards and confirmed by gas chromatography-mass spectrometry using electron-impact ionisation. Fatty acid methyl esters were quantified in absolute amounts with respect to dry tissue weight and as a percentage of the total fat. Statistical analysis of the results from twenty healthy subjects using the two-tailed unpaired Student's t-test demonstrated women had significantly higher levels of myristoleic and palmitoleic acids (p less than 0.001) and lower levels of palmitic acid (p less than 0.05) in adipose tissue when compared with the male group. Similarly total saturated fatty acids was lower (p less than 0.05) and total monounsaturated fatty acids was higher in women than in men.
Adipose Tissue↗
Correction of subclinical ascorbate deficiency in patients receiving dialysis: effects on plasma oxalate, serum cholesterol, and capillary fragility.
Whole blood ascorbate, plasma oxalate, serum cholesterol, and capillary fragility were measured at monthly intervals for 3 mth in 7 patients receiving continuous ambulatory peritoneal dialysis and 4 receiving haemodialysis, to whom ascorbate supplements had not been prescribed for at least 12 mth. Ascorbate supplements, 25 mg/day, were prescribed for the first month and 50 mg/day for the second month; in the final month patients received no supplements. Whole blood ascorbate was below normal in 6/11 patients at the start of the study but was normal in 10/11 patients when taking ascorbate 50 mg/day. No significant changes in plasma oxalate were observed with these doses of ascorbate, and correction of ascorbate deficiency had no effect on serum cholesterol, mean cell volume, or the results of capillary fragility tests. In a supplementary study, ascorbic acid 500 mg/day was administered for 3 wk to 11 patients. This resulted in a significant rise in mean plasma oxalate from 30.3 (SEM 3.5) to 48.4 (SEM 20.3) mumol/l.
Ascorbic Acid↗
The determination of plasma oxalate concentrations using an enzyme/bioluminescent assay. 2. Co-immobilisation of bioluminescent enzymes and studies of in vitro oxalogenesis.
An inexpensive, continuous flow assay for the determination of oxalate in plasma is described. The assay is based on the bioluminescent determination of NADH, a product of the degradation of oxalate by oxalate decarboxylase and formate dehydrogenase, using bioluminescent enzymes immobilized on cyanogen bromide-activated sepharose. The detection limit of the assay is 0.8 mumol/l. Intra-batch CV values of 5.2 and 3.8% were obtained at oxalate concentrations of 18 and 60 mumol/l. Recovery of added oxalate averaged 100.7%. Plasma oxalate ranged from less than 0.8 to 2 mumol/l in 14 healthy subjects, and from 6 to 134 mumol/l in 125 patients with renal disease treated by continuous ambulatory peritoneal dialysis. Ascorbic and dehydroascorbic acid did not directly interfere in the assay. In vitro oxalogenesis was observed in blood from 12 healthy subjects, but only after samples had stood at room temperature for more than 6 h. No significant oxalate generation occurred in blood from 24 patients with impaired renal function, even after standing at room temperature for 24 h. Oxalate generation was inhibited by the addition of oxalate to plasma, but the addition of urea and creatinine was without effect.
Creatinine↗
Active and passive sugar absorption in pancreatic insufficiency.
Urinary excretion of lactulose, mannitol, and 3-0-methylglucose, following oral administration (5 g, 5 g, and 2 g, respectively, in 100 ml H2O; 80 ml/m2), has been measured in subjects with cystic fibrosis (CF) (22), Shwachman syndrome (3), chronic pancreatitis (3), and normal controls (46). Mean lactulose excretion was increased 10-fold in CF (p less than 0.001), and two-fold in other disorders associated with pancreatic insufficiency (PI) (p less than 0.05). Mean mannitol excretion was 1.6 times greater in CF (p less than 0.001), compared with controls, but was reduced in other forms of PI (p less than 0.03). The mean lactulose/mannitol excretion ratio was increased in all types of PI (p less than 0.001). There were no significant differences in 3-0-methylglucose excretion. This study confirms the large increase in lactulose absorption recently reported in CF and also demonstrates increased absorption of mannitol; these changes are different than those in other forms of PI. This study provides further evidence for a specific abnormality of the mucosal barrier to the absorption of passively absorbed, water soluble molecules in CF.
3-O-Methylglucose↗
Within-clinic reagent strip lipid measurement.
The agreement between the Reflotron dry chemistry analyser and laboratory methods for measurement of total cholesterol and triglycerides was assessed by studying the between-method variability for individual samples. A paired comparison of replicate measurements from venous blood was made for 105 cholesterol and 90 triglyceride specimens. There was no significant mean difference between the two methods for cholesterol measurement (difference 0.02 mmol l-1, 95% Cl -0.07 to 0.10 mmol l-1) but there were wide limits of agreement (+/- 2SD) of -0.87 to 0.90 mmol l-1. Some of the differences in measurement were large enough to be clinically misleading and would result in inconsistencies in diagnostic assignment between the two methods. Both methods achieved relatively poor repeatability which limited the agreement possible (coefficient of repeatability, defined as 2SD of the differences, 0.59 mmol l-1 for the Reflotron and 0.38 mmol l-1 for the laboratory). The repeatability of triglyceride measurement was similar for the Reflotron and laboratory (coefficient of repeatability 0.24 mmol l-1 and 0.27 mmol l-1, respectively). However, there was a significant systematic difference between methods, with the Reflotron reading 0.30 mmol l-1 less than the laboratory method (95% Cl 0.26 to 0.35 mmol l-1) and the limits of agreement between the methods were -0.09 to 0.70 mmol l-1. It is important that clinicians recognize the limits of agreement between dry chemistry analysers and laboratory methods and take these into account when using them to screen for hyperlipidaemia or to monitor treatment of hyperlipidaemic diabetic patients.
Cholesterol↗
Intestinal permeability tests and integrity of the small intestinal mucosa.
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Child↗