Biomedical subjects

H G Parsons

Publications and source records attributed to H G Parsons.

At least 37 records · Page 2Linked to original sources

PubMed1995

A marked and sustained reduction in LDL sterols by diet and cholestyramine in beta-sitosterolemia.

This study examines the therapeutic outcome of a low plant sterol diet and adjunctive drug therapy (cholestyramine) in the long term treatment of beta-sitosterolemia. A diet restricted in plant sterols, cholesterol and fat was implemented in a 48-year-old male beta-sitosterolemic patient. The plant sterols beta-sitosterol, campesterol and stigmasterol, and cholesterol content of the diet were quantitated by a gas chromatography method (GLC) during metabolic ward studies. Food table analysis of dietary sterols, while quantitatively similar to GLC, significantly underestimated the level of plant sterols and therefore overestimated dietary cholesterol intake. The duration of the study was 18 months. The effect of the diet over a period of 6 months on the sterol levels of plasma and individual lipoprotein fractions (VLDL, LDL, HDL) was evaluated. Apolipoproteins A-1 and B-100 levels were measured. The same parameters were assessed over the next 12 months with the adjunctive use of cholestyramine and dietary restrictions. The diet was effective in lowering total, VLDL, and LDL plant sterols by 37%, 59%, and 32% respectively. The low plant sterol diet did not change total plasma, VLDL or LDL cholesterol. With the addition of cholestyramine, total plasma and LDL cholesterol declined by 64 and 76%, respectively, while HDL-cholesterol remained unchanged. LDL plant sterols declined by 77%, while VLDL plant sterol showed no further change. The decline showed no discrimination among the individual plant sterols. One week after cholestyramine therapy, apolipoprotein B fell from 1.03 to 0.11 g/L, while apolipoprotein A rose from 1.29 to 1.79 g/L. These levels subsequently stabilized at 70% below (0.29 g/L) and 42% above (1.81 g/L) that of diet therapy alone. Xanthomas, angina pectoris, and intermittent claudication resolved during the diet and cholestyramine therapy period. Dietary restriction of plant sterols combined with cholestyramine therapy is an effective means of treating beta-sitosterolemia.

Adult↗

PubMed1994

Bile salts determine leukotriene B4 synthesis in a human intestinal cell line (CaCo-2).

The ability of a human colonic epithelial cell line (CaCo-2) to synthesize leukotriene B4 (LTB4) in response to bile salt stimulation was examined, as was the dependency of such stimulation on the hydrophobic-hydrophilic balance of the bile salts. We demonstrate for the first time in this human intestinal epithelial cell line the ability of bile salts to stimulate synthesis of LTB4. CaCo-2 cell monolayers were incubated with a series of bile salts ranging in concentration from 0.5 microM to 1 mM. This resulted in a dose- and hydrophobicity-dependent increase in LTB4 synthesis. Hydrophobic bile salts (glycine and taurine conjugates of lithocholate and deoxycholate) caused LTB4 synthesis to be stimulated 27% and 35%, respectively, above control levels. In contrast, hydrophilic bile salts (glycine and taurine conjugates of ursodeoxycholate) increased LTB4 synthesis only 11.2% and 16.1%. Under basal conditions pretreatment with dexamethasone significantly inhibited bile salt-induced LTB4 synthesis by 38% compared to control. With more hydrophobic bile salts, chenodeoxycholate and deoxycholate, dexamethasone inhibited LTB4 synthesis to levels significantly below those observed with dexamethasone under basal conditions. Unlike A23187 calcium ionophore-induced LTB4 synthesis, bile salt-induced stimulation of LTB4 synthesis was not found to be dependent on the presence of extracellular calcium. Variations in bile salt stimulation of LTB4 by intestinal epithelial cells could be important in modulating cellular responses. The synthesis of chemotactic factors, such as LTB4, by the human colonic adenocarcinoma epithelial cell line now needs to be extended to normal human intestinal epithelium, as it may play a role in many of the functional disturbances which characterize intestinal inflammatory conditions.

Adenocarcinoma↗

PubMed1994

Influence of dietary fat on the pharmacodynamics of quinidine, procainamide and tocainide in isolated perfused rabbit hearts.

We have reported previously that propafenone decreased ventricular excitability and prolonged ventricular conduction time in hearts from rabbits treated with a lard diet compared to those from rabbits treated with a safflower oil diet. We hypothesized that these effects might be modulated by the lipid solubility of the drug. Accordingly, we studied the effects of dietary fat on the pharmacodynamics of the hydrophilic drugs, procainamide and tocainide, and the lipophilic drug, quinidine. Weanling rabbits were fed diets of 10% w/w lard or safflower oil for 40 days. Differences in electrophysiological variables were compared at base line and during drug perfusion. The linoleic acid content of isolated sarcolemma was significantly higher in the safflower oil group (31.1 +/- 5.6%) than in the lard group (18.8 +/- 3.9%, P < .001). During quinidine (3 microM) perfusion, the threshold current was significantly greater in the lard group (0.44 +/- 0.18 mA) compared to the safflower oil group (0.24 +/- 0.11 mA, P < .05). During procainamide and tocainide perfusion, the threshold current was similar in the lard and safflower oil groups. During quinidine perfusion, greater prolongation of the endocardial monophasic action potential duration was observed in the safflower oil group (217 +/- 15 msec) compared to the lard group (196 +/- 24 msec, P < .05). Procainamide and tocainide effects on monophasic action potential duration were similar in the lard and safflower oil groups. Thus, dietary fat modulates the effects of the lipophilic drug quinidine on ventricular excitability and repolarization.

Action Potentials↗

PubMed1992

Modulation of cellular phospholipid fatty acids and leukotriene B4 synthesis in the human intestinal cell (CaCo-2).

The ability of a human colonocyte epithelial cell line (CaCo-2) to synthesise leukotriene B4 was examined. In addition, the effects of stimulation with calcium ionophore, inhibition by a drug which specifically prevents activation of 5-lipoxygenase, and modification of the fatty acid composition of membrane phospholipids on leukotriene B4 synthesis were assessed. Incubation with calcium ionophore (A23187) resulted in a dose and time dependent increase in leukotriene B4 synthesis. After cell phospholipids had been enriched with oleic acid, linoleic acid, and arachidonic acid, leukotriene B4 synthesis was found to be increased 3.2-fold, 5.5-fold, and 6.1-fold above control. Treatment with MK-886 inhibited leukotriene B4 synthesis by 79% to 94% in the various groups. Variations in the polyunsaturated fatty acid content of intestinal epithelial cells could be important in the modulation of cellular responses. We have shown for the first time in this human intestinal epithelial cell its ability to synthesise leukotriene B4. In addition, leukotriene B4 synthesis can be modulated by the fatty acid composition of membrane phospholipids, which can be altered by dietary fatty acids. The synthesis of chemotatic factors, such as leukotriene B4, by the mucosal epithelium may contribute to the recruitment of granulocytes into the colonic mucosa and across the epithelium, giving rise to the crypt abscesses which characterise ulcerative colitis.

Calcimycin↗

PubMed1992

Significance of phototherapy-induced riboflavin deficiency in the full-term neonate.

As a result of impaired fatty acid oxidation, a characteristic urinary dicarboxylic aciduria occurs in the riboflavin deficient animal. We compared the occurrence of riboflavin deficiency induced by phototherapy with changes in urinary organic acid profiles in 8 full-term, breast-fed neonates who received phototherapy for hyperbilirubinemia, and in 10 full-term, breastfed controls. Riboflavin status was assessed by measuring flavin adenine dinucleotide saturation of erythrocyte glutathione reductase. All 8 neonates exposed to phototherapy developed riboflavin deficiency (p less than 0.001). Riboflavin deficiency was progressive with the duration of phototherapy. None of the controls was riboflavin deficient. Urine organic acid profiles indicative of mitochondrial acyl-CoA dehydrogenase activity (fatty acid beta-oxidation, quantitated by gas chromatography mass spectrometry) showed no changes between the study and control groups in mono-, di-, or tricarboxylic acids or other organic acids. The riboflavin deficiency induced by phototherapy in full-term neonates was not of sufficient severity to limit riboflavin-dependent fatty acid oxidation.

Birth Weight↗

PubMed1992

Influence of dietary fat on the pharmacodynamics of propafenone in isolated, perfused rabbit hearts.

BACKGROUND: The fatty acid composition of the phospholipids in sarcolemma may significantly influence cell membrane functions. We evaluated the effects of dietary fat on the pharmacodynamics of the antiarrhythmic drug propafenone in isolated, perfused rabbit hearts. METHODS AND RESULTS: Three groups of weanling rabbits (n = 9 each group) were fed diets of 10% wt/wt lard, fish oil, or safflower oil for 40 days. Differences in electrophysiological variables were assessed at baseline and during propafenone perfusion. Myocardial concentration-effect relations were determined by plotting electrophysiological effects versus coronary sinus propafenone concentrations. The linoleic acid content of isolated sarcolemma was higher in the safflower group (33.4 +/- 11.4%) than in the lard (13.4 +/- 2.3%, p less than 0.01) and fish oil (8.5 +/- 1.4%, p less than 0.01) groups, whereas the omega-3 fatty acid content was higher in the fish oil group (p less than 0.01). During propafenone perfusion, greater changes in ventricular conduction time were observed in the lard group (22 +/- 11 msec) than in the safflower oil group (10 +/- 7 msec, p less than 0.05), whereas changes in ventricular conduction time in the fish oil group (16 +/- 7 msec) were intermediate between the lard and safflower oil groups. The slopes of the linear myocardial concentration-effect relations describing changes in QRS duration were steeper in the lard group (0.22 +/- 0.07 msec/micrograms/ml) than in the safflower oil group (0.13 +/- 0.04 msec/micrograms/ml, p less than 0.01) but not in the fish oil group (0.17 +/- 0.08 msec/microgram/ml, p = NS). Strength-interval curves were similar at baseline in all three groups. During propafenone perfusion, the threshold current was increased significantly at long coupling intervals (250-380 msec) in the lard group (1.8 +/- 1.0 mA) compared with the safflower oil group (0.8 +/- 0.6 mA, p less than 0.05) but not compared with the fish oil group (1.2 +/- 0.6 mA, p = NS). CONCLUSIONS: Dietary fat significantly alters the fatty acid composition of the phospholipids in sarcolemma. Propafenone effects on ventricular conduction time and ventricular excitability are significantly influenced by the type of dietary fat.

Animals↗

PubMed1991

Nondairy-creamer-induced kwashiorkor: 5-year follow-up.

Failure to thrive may not be a result of organ disease, physical abuse, or intentional neglect. We describe an infant who developed kwashiorkor with a high-fat, low-protein, nondairy coffee creamer diet. The elimination diet was administered on the advice of a family friend for a facial rash. The child presented at 10 months of age with decreased weight for height, rash, hepatomegaly, edema, hypoproteinemia, hypoalbuminemia, anemia, hypoglycemia, and evidence of hepatic sequestration of lipids. A rapid recovery of biochemical abnormalities was evident on reinstitution of a full diet. An intellectual assessment at age 5 years showed normal results.

Female↗

PubMed1991

Intramitochondrial fatty acid metabolism: riboflavin deficiency and energy production.

Inborn errors of fatty acid beta-oxidation have contributed significantly to our understanding of intracellular fatty acid metabolism. The first intramitochondrial step in beta-oxidation of fatty acyl-CoA of different chain lengths is catalyzed by the three chain length specific acyl-CoA dehydrogenases. Inherited deficiency of these enzymes has been reported. Some are riboflavin responsive. The first step of fatty acid oxidation is reviewed with specific emphasis on beta-oxidation in newborn infants, rendered riboflavin deficient by phototherapy. Given that medium chain fatty acids are not stored as triacylglycerols and undergo rapid beta-oxidation, they have been proposed as superior substrates compared with long chain triglycerides in times of metabolic stress. This review also examines medium chain triglycerides as an alternate energy source. When medium chain triglycerides were fed as 50% of total energy, glucose sparing was present with little loss of energy as dicarboxylic acids.

Acyl-CoA Dehydrogenase↗

PubMed1991

Postprandial hyperglycemia and pancreatic function in cystic fibrosis patients.

Pancreatic endocrine function was studied in 50 patients with cystic fibrosis (CF) and 15 healthy controls by measuring glucose, insulin, C-peptide, glucagon and gastro-inhibitory polypeptide responses to an oral glucose tolerance test (OGTT). Biochemical and clinical parameters were also measured, including glycosylated hemoglobin A1, serum immunoreactive trypsin, fasting urinalysis, pulmonary function, percentage body fat and 3-day dietary records. According to National Diabetes Data Group (NDDG) criteria, 6 CF patients had impaired glucose tolerance (ICF), with elevated serum glucose concentrations and reduced and delayed insulin secretion compared with control (CON) subjects, although none were overtly diabetic. Although the remaining 44 CF patients (NCF) did not meet NDDG criteria for impaired glucose tolerance, mean area under the concentration curve (AUC) for glucose was greater than control values and AUC for insulin diminished. HbA1 levels in the 2 CF groups were greater than that of controls subjects, but there was little difference between ICF and NCF groups. C-peptide levels paralleled those of insulin for the 3 groups throughout OGTT. There was little difference in GIP secretion between groups, and the enteroinsular axis was intact in the control and NCF groups and slightly increased in the ICF group. Basal glucagon concentrations and AUC for glucagon during OGTT were similar for the 3 groups, but glucose-induced glucagon suppressibility i.e., basal to nadir change in each subject, was reduced in the ICF group. Serum IRT concentration was significantly lower in the ICF and NCF groups compared to control subjects, and was lowest in the ICF group. A strong correlation was observed in the ICF group between FEF25-75 and AUC for insulin, as well as HbA1 level and AUC for glucose. The prevalence of impaired glucose tolerance in 50 CF patients was 12%. Despite extensive comparisons of biochemical and clinical parameters with endocrine function in this population, we were unable to define reliable criteria for predicting glucose intolerance.

Adolescent↗

PubMed1990

Evaluation of branched-chain amino acid intake in children with maple syrup urine disease and methylmalonic aciduria.

The biochemical and growth responses to dietary branched-chain amino acid (BCAA) intake were studied in two children; one with a disorder of branched-chain amino acid metabolism, maple syrup urine disease (MSUD) (McKusick 24860), and another with methylmalonic aciduria (MMA) (McKusick 25100). Biochemical control of MSUD focussed on plasma leucine levels while measurement of plasma ammonia levels was used in MMA. From 0 to 2.75 years both patients exhibited five episodes of toxicity. In each case toxicity was associated with dietary indiscretion or infection. The quantity of protein tolerated was always less in the MMA patient and was approximately 1 g/kg/day. From 1 to 2.75 years each patient's growth velocity approximated their predicted growth channel except during periods of toxicity. In both cases leucine intake, which gave normal growth without toxicity, was always judged to be less than the FAO/WHO recommendations. The BCAA intake of the MMA patient was remarkably stable from 0.5 to 2.75 years and at 2 years of age isoleucine and valine intake approximated the FAO/WHO recommendations. From 2 to 2.75 years BCAA intake (mg/kg/day) of the MSUD patient was less than that of the MMA patient and well below FAO/WHO recommendations. Neuromotor development in both patients is normal.

Amino Acid Metabolism, Inborn Errors↗

PubMed1990

Effects of medium-chain triglyceride feeding on energy balance in adult humans.

In recent years, the metabolism of triglycerides has attracted much attention. Oxidation of fatty acids is an essential energy supply, especially when glucose supply is limited. In the present study, the effect of a 3-day high medium-chain triglyceride (MCT; 51% of calories), low carbohydrate intake on plasma glucose and amino acid, and urinary organic acid levels, including dicarboxylic and tricarboxylic acid cycle intermediates, was determined in eight normal adult volunteer subjects. Urine was collected at baseline and at 48 to 72 hours for amino acid and organic acid levels, and plasma collected at 0 and 72 hours for glucose and amino acid concentration. The MCT diet increased urinary levels of dicarboxylic acids (adipic 8-, suberic 65-, sebacic 284-fold) and keto acids (acetoacetate and beta-hydroxybutyrate, 67.5-fold); alanine and lactate were decreased 2.5- and 4-fold, respectively, while pyruvate, other amino acids and citric acid intermediates remained unchanged. Plasma amino acid levels were unchanged, while the plasma glucose levels decreased by 8% from baseline. The loss of calories as urinary dicarboxylic acids and keto acids, although increased during the MCT diet, was less than 1% of the daily caloric intake. The data suggest MCT sustain energy expenditure through medium-chain fatty acid (MCFA) oxidation with no decrease in citric acid cycle intermediates, while sparing protein oxidation.

Adult↗

PubMed1990

Absorption of triglycerides in the absence of lipase.

Medium chain triglycerides are considered to be readily absorbed intact in the absence of pancreatic lipase, unlike long chain triglycerides. Commercial medium chain triglyceride oils comprise various medium chain fatty acids from 6 to 12 carbons in length resulting in triglyceride molecules of different sizes and molecular weights. The effect of molecular weight and hence fatty acid chain length on the efficiency of intact medium chain triglyceride absorption is unknown. Therefore, this study measured, using a single-pass marker perfusion technique, intestinal jejunum absorption of five medium chain and one long chain triglycerides in anesthetized Sprague-Dawley rats. The molecular weights of the five medium chain triglycerides were 470.7, 498.8, 526.8, 554.9, 639.0, and the long chain triglyceride, 885.4. Residual luminal pancreatic lipase was removed prior to lipid perfusion. This study demonstrated that medium chain triglycerides were absorbed in the absence of lipase whereas long chain triglyceride was not. There was no significant variation in the absorption of the five different medium chain triglycerides perfused. The molecular weight of the medium chain triglyceride did not affect its intact absorption by the small intestine.

Animals↗

PubMed1990

Stable isotopes in the management and diagnosis of inborn errors of metabolism.

Stable isotope techniques offer advantages over older methods in safety, sensitivity, specificity, and reduction in number of subjects required for analytic determinations in some types of studies in "inborn errors of metabolism." In addition to their use as internal standards for gas chromatography - mass spectrometry, quantitation of plasma substrates, and their urinary metabolites, stable isotopes have been successfully employed in studies of metabolite identification, enzyme activity, nutrient turnover and requirements, and diagnosis of inborn errors of metabolism.

Animals↗

PubMed1989

Effect of cyclosporin A on serum lipids in primary biliary cirrhosis patients.

Hyperlipidemia is a common complication of PBC. Ten patients with serologically and histologically defined PBC were randomized to receive either oral cyclosporin A (CyA) or placebo for one year. Fasting blood samples were obtained from subjects at the beginning, and following one year of treatment, for plasma lipids, apolipoproteins AI (apo AI) and B (apo B), and lecithin-cholesterol acyltransferase (LCAT) activity. On entry to the study there were no significant differences between groups for serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free cholesterol (FC), total phospholipids (TPL), apo AI, apo B and LCAT activity. Compared to normal laboratory values, baseline TC was elevated in 5/10, LDL-C in 5/10, TPL in 6/10, while LCAT activity was decreased in 8/10 patients. The percent change after one year for CyA group vs the placebo group are as follows: total cholesterol, -22 vs -8%; LDL cholesterol -33 vs -25%; free cholesterol, -39 vs -14%; total phospholipids, -46 vs -23%; and LCAT activity, +/- 236 vs +/- 43%. The decrease in TC, LDL-C, FC, TPL with increase in LCAT activity suggests that CyA administration is associated with improvement in the lipid abnormalities of PBC.

Adult↗

PubMed1988

Supplemental calories improve essential fatty acid deficiency in cystic fibrosis patients.

Fatty acid composition of plasma lipids was analyzed in malnourished cystic fibrosis patients undergoing 6 months of nutritional rehabilitation. There were three males and five females (mean age 15.1 yr); five patients had pancreatic insufficiency. Nutritional rehabilitation in seven of eight patients was accomplished by nocturnal nasogastric infusion of a high-carbohydrate semisynthetic diet, in addition to daily meals. One patient received high-energy food supplements as snacks in addition to regular meals. All patients were moderately to severely malnourished on entry to the study and showed significant improvement over the 6 months in (means +/- SE) energy intake (96 +/- 8.0 to 126 +/- 11% recommended daily allowance) and body composition (80 +/- 4 to 90 +/- 4% ideal body weight). Daily intakes of linoleic acid were not significantly different before or during nutritional rehabilitation either as an absolute amount (383 +/- 45 to 557 +/- 124 mg/kg/day) or as a percentage of total calories (4.50 +/- 0.40 to 4.73 +/- 0.14%). In comparison to the controls, the relative percentage of plasma cholesterol ester fatty acids of the CF patients on entry into the study showed a marked decrease of linoleic acid (52.7 +/- 1.0 versus 42.3 +/- 2.7%) with elevated palmitoleic (2.34 +/- 0.2 versus 5.64 +/- 0.7%) and oleic (18.7 +/- 1.0 versus 25.2 +/- 1.4%) acids; a pattern consistent with essential fatty acid deficiency. However, this pattern is not truly characteristic of a pure linoleic acid deficiency as the metabolites of linoleic acid were not decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

Dual-precipitation method evaluated for determination of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol concentrations.

We evaluated a dual-precipitation method for determining cholesterol in high-density lipoprotein (HDL) and its subfractions HDL2 and HDL3. After total HDL was isolated by precipitation of very-low-density (VLDL) and low-density (LDL) lipoproteins with polyethylene glycol (Mr 8000), HDL2 was isolated from total HDL by precipitation with dextran sulfate (Mr 15,000), leaving HDL3 in the supernate. Concentration of total HDL cholesterol after precipitation of VLDL and LDL with PEG showed significant proportional and constant biases of -3.8% and 0.04 mmol/L, respectively, when compared with a phosphotungstic acid-based comparison method, although results by the two methods were correlated highly (r = 0.99, P less than 0.001). HDL2 and HDL3 cholesterol concentrations measured with the present technique were not different from those obtained by density-gradient ultracentrifugation or by combined precipitation-ultracentrifugation.

Centrifugation, Density Gradient↗

PubMed1987

Argininosuccinic aciduria: long-term treatment with arginine.

The presentation and 2 year treatment of a patient with argininosuccinic aciduria is reported. Erythrocyte argininosuccinate lyase activity was less than 2% of normal. Long-term management included protein restriction and arginine dietary supplementation. The child experienced three episodes of hyperammonaemia (greater than 100 microns), the first at birth, the second at 6.5 months and the third at 16 months. Neurological development deteriorated between 14 and 24 months. Hepatomegaly and biochemical hepatitis, a feature of this condition, was accompanied by enlarged mitochondria with tubular paracrystalline inclusions not previously recognized in this disorder.

Amino Acid Metabolism, Inborn Errors↗

PubMed1986

Modulation of human erythrocyte shape and fatty acids by diet.

A semi-synthetic diet (Vivonex) was administered via nasogastric tube to three cystic fibrosis patients with pancreatic exocrine deficiency for 14 days to gain weight. Dietary essential fatty acids were provided as safflower oil, which constituted 1.3% of total calories. Plasma and red blood cells were analyzed for the content and composition of lipids at the start of the diet and at days 7 and 14 of the dietary period, and the results were correlated with the morphology of the cells. Feeding Vivonex to the patients led to an essential fatty acid deficiency, which was manifested in a 50% decrease in the linoleic acid content of the phosphatidylcholine of plasma and red blood cells at days 7 and 14 and in a 20% decrease in the linoleic acid content of red cell phosphatidylethanolamine at day 14. There was no significant alteration in the levels or composition of the other phospholipid classes and in the free cholesterol/phospholipid ratio. The decrease in the linoleic acid content of the erythrocytes was accompanied by a dramatic increase in the proportion of cells as echinocytes. We conclude that restricted linoleic acid availability in cystic fibrosis patients causes a change in red blood cell shape either directly by decreasing the linoleoylphosphatidylcholine content of the membrane or indirectly by affecting enzyme activity.

Adolescent↗