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Biomedical subjects

D I Thurnham

Publications and source records attributed to D I Thurnham.

At least 73 records · Page 4Linked to original sources
PubMed1990

Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.

The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation.

Antioxidants↗
PubMed1990

Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma.

A series of experiments are described which show that second derivative spectroscopy can be used to quantify conjugated lipid dienes as markers of lipid peroxidation in heptane extracts of plasma from patients with rheumatoid arthritis, osteoarthritis, and healthy controls. Results obtained by this method gave reasonable agreement with those derived from the measurement of simple absorbance in chloroform/methanol extracts. Two minima were observed in the derivative spectrum of plasma lipid extracts. These minima occurred at 233 and 241 nm and corresponded to absorbance maxima in the conventional UV spectrum. Using a combination of phospholipase hydrolysis, reverse phase high performance liquid chromatography (HPLC) and second derivative spectroscopy we confirmed that these two minima can be attributed to a single fatty acid (9 cis-, 11 trans-linoleic acid) shown previously to account for greater than 90% of diene conjugation in human plasma samples. When the biological isomer 9 cis-, 11 trans-linoleic acid was separated by reverse phase HPLC from the mixture of other plasma phospholipid-2-esterified fatty acids we observed a change in derivative spectroscopy minima from 233 and 241 nm to 228 and 237 nm. Minima at the latter two wavelengths were also seen with pure preparations of the Paint Research Isomer (9 trans-, 11 trans-linoleic acid) which eluted later than biological 9 cis-, 11 trans-linoleic acid using reverse phase HPLC, suggesting that the absorption spectra of these pure cis-, trans and trans, trans dienes are similar but can be altered by the presence of other fatty acids in the extract.

Adult↗
PubMed1989

Vitamins, iron, and physical work.

Combined marginal deficiencies of iron, vitamin C, and B-group vitamins are widespread in developing countries. An understanding of the functional implications poses a continuing challenge, both for the development of new techniques of investigation and for the design of effective intervention programmes. Practical intervention in developing countries also needs to take account of the interactions of micronutrient status and disease susceptibility. It is becoming clear that combined deficiencies of certain vitamins, or of iron and vitamins, although less severe than those causing the lesions of classic clinical deficiency, can seriously reduce work performance. Riboflavin, particularly, has a special relation with iron economy.

Adolescent↗
PubMed1989

Reduced antioxidant capacity in paediatric patients with homozygous sickle cell disease.

The sickled erythrocyte has been shown to be susceptible to lipid peroxidation and a role has been suggested for antioxidants in this process. The present study was undertaken in 22 children, aged 5-18 years with homozygous sickle cell disease (SS) and 9 HbAA controls (AA) of similar age. All the SS patients were in steady state ie, not in crisis or any acute illness at the time of the study. Levels of plasma tocopherol, retinol, carotenes and ascorbic acid (antioxidant vitamins of major nutritional importance) were measured. Plasma tocopherol carotenes and retinol were measured by HPLC after extraction into heptane. Total ascorbic acid (in trichloroacetic acid extracts of plasma) was measured colorimetrically following reaction with 2,4-dinitrophenylhydrazine. Riboflavin status was measured by the glutathione reductase activation test. Levels of all the measured antioxidants except ascorbate were reduced in SS patients compared with control children but only plasma alpha-tocopherol concentration was significantly different between the patients and controls. The median tocopherol level in SS patients (11.32 mumol/l) was significantly lower (P less than 0.02 Mann-Whitney) than that in control children (18.02 mumol/l) when measured directly or when calculated from tocopherol: cholesterol ratio, 4.55 mumol/mmol in SS patients and 7.50 mumol/mmol in control children. The median concentration of total plasma carotenes of SS patients (5.67 mumol/l) was lower than that of control children (12.14 mumol/l). Similarly, plasma beta-carotene concentration of SS patients was lower than that of control children but the difference in each case was not significant. Despite this, the vitamin A status (plasma retinol concentration) of SS patients was poorer than that of control children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Blood, retinol and zinc riboflavin status in relation to precancerous lesions of the esophagus: findings from a vitamin intervention trial in the People's Republic of China.

Data from a double-blind intervention trial in China are reanalyzed to explore auxiliary information. The trial had shown that in a high-risk area for esophageal cancer the dietary supplementation of apparently healthy individuals with a combination of retinol, riboflavin, and zinc did not lead to a different prevalence of precancerous lesions of the esophagus among those receiving the active treatment compared to a placebo group. However, improvement of blood retinol and zinc levels were also observed in the placebo group. The logistic regression analysis presented in this paper illustrates that those individuals who showed large increases in retinol, riboflavin, and zinc blood levels were more likely to have a histologically normal esophagus at the end of the trial. This effect is clearer for retinol than for riboflavin and zinc and it is independent of whether the change was caused by the active treatment or occurred otherwise.

Adult↗
PubMed1988

Nutritional and haematological status of Chinese farmers: the influence of 13.5 months treatment with riboflavin, retinol and zinc.

A retinol (15 mg), riboflavin (200 mg) and zinc (50 mg) supplement or a placebo (D-mannitol) was given to 610 Chinese farmers weekly for 13.5 months. Riboflavin, retinol, beta-carotene, tocopherol and zinc status were measured in all subjects at the start and end of the intervention and in a subsample at 2 months. Plasma vitamin C, haemoglobin and haematocrits were measured on other subsamples at the end of the supplementation period. At the start vitamin A, zinc and riboflavin status were poor. Plasma retinol and zinc concentrations were higher in men than women but the opposite was observed with respect to beta-carotene. There was no difference between the sexes for tocopherol and riboflavin. Tocopherol:cholesterol ratios suggested vitamin E status was good and vitamin C status also appeared adequate. The supplement increased plasma retinol throughout the whole period but riboflavin status improved only over the first 2 months and then remained constant. Plasma zinc increased in both treatment and placebo groups by approximately 15 to 20 per cent in men and women. Mean concentrations of retinol and tocopherol and beta-carotene (in women only) increased by approximately 20 per cent in the placebo group. It is argued that seasonal factors and/or the placebo may have been responsible for the increase in retinol and beta-carotene in the placebo group. The lack of an increase in beta-carotene in the men may have been due to their higher retinol requirements. Lastly, the increase in retinol may have been responsible for the increase in tocopherol and zinc in plasma since these nutrients increased in those whose plasma retinol increased, irrespective of treatment.

Adult↗
PubMed1988

Concurrent liquid-chromatographic assay of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthin in plasma, with tocopherol acetate as internal standard.

A method is described for simultaneously determining retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthin in 0.25 mL of plasma. Plasma mixed with sodium dodecyl sulfate is deproteinized with ethanol containing tocopherol acetate, then extracted with heptane. The evaporated organic layer is reconstituted with mobile phase (methanol/acetonitrile/chloroform, 47/47/6 by vol) and injected onto a 100 x 4.6 mm 3-micron column of Spherisorb ODS-2 (LKB) at 1.5 mL/min. The alpha- and beta-carotenes are well resolved during the 6.5-min run. Retinol is monitored at 325 nm, the tocopherols at 292 nm, and the carotenoids at 450 nm. Extraction of concentrations as great as 135 mumol/L is complete. Intrabatch CVs were 1.7%, 2.3%, 4.1%, 10.4%, 6.4%, and 3.6% for retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthin, respectively. Interbatch CVs for measurements on 30 occasions over 11 weeks were about 10% for all components except alpha-tocopherol (5.3%). Results agree well with those for retinol, alpha-tocopherol, and beta-carotene in quality-control samples.

Carotenoids↗
PubMed1987

Dependence of pyridoxine metabolism on riboflavin status in sickle cell patients.

The relationship between riboflavin and pyridoxine status was studied in 40 patients with sickle cell disease (SCD) and 12 normal children by measuring activation coefficients of erythrocyte glutathione reductase (EGRAC) and aspartate transaminase (ASTAC). Prevalence of riboflavin deficiency was significantly lower in SCD (42.5%) than in control subjects (83%) and there was less pyridoxine deficiency in SCD (10.3%) than control subjects (54.5%). Aspartate transaminase (AST) activities in SCD patients were double those in control subjects. Pyridoxine status of patients, but not of control subjects, was directly affected by riboflavin status as judged from significant correlations between EGRAC and both AST activity and ASTAC. Poor riboflavin status in patients may be restricting availability of pyridoxal phosphate (PLP) due to combined effects of enhanced PLP requirements and effects of poor riboflavin status on the synthesis of PLP by pyridoxine phosphate oxidase (PPO). PPO activity was no different in the two groups.

Adolescent↗
PubMed1987

Evidence for lipid peroxidation in man following paraquat ingestion.

Four patients were investigated for evidence of lipid peroxidation between 4.5 and 36 h (mean 22 h) after ingestion of paraquat by measuring plasma phospholipid-2-esterified, diene-conjugated 18:2 delta 9,11-linoleic acid (9,11-LA) and expressing it also as a ratio R (9,11-LA/9,12-LA X 100) of the 'parent' linoleic acid. The mean value for R was 4.73 (range 3.7-7.1) at presentation and 6.91 at peak values (range 3.8-13.4) which occurred at a mean of 34 h after ingestion. Both values were significantly higher (P less than 0.001) than that of 107 healthy controls (1.94, range 0.67-3.8). Parallel changes in plasma vitamin E and 9,11-LA occurred in the 2 patients in whom serial measurements were made suggesting an involvement of vitamin E in the formation of this isomer. These findings support the hypothesis that lipid peroxidation occurs during paraquat poisoning in man and the early appearance of 9,11-LA suggests that it may be a primary event.

Adult↗
PubMed1986

The influence of riboflavin deficiency on absorption and liver storage of iron in the growing rat.

1. Iron absorption was measured in weanling riboflavin-deficient (RD) rats or weight-matched (WM) controls fed on appropriate diets for 7 weeks. Concentrations of radio-Fe (59Fe) in plasma were monitored every 30 min for 4 h following intragastric administration. 2. Total Fe absorption in RD rats was significantly lower than that in WM controls, and the tissues of the stomach and small intestine of RD rats retained significantly (P less than 0.001) more 59Fe by comparison with WM groups. 3. In a separate experiment, ferritin-Fe concentrations were measured in the livers of four groups of rats (ad lib. (C), pair-fed (PF) and WM controls and RD) at day 0, and subsequently at days 14, 21, 28, 35 and 49. 4. Liver ferritin-Fe concentration was significantly lower (P less than 0.05) in RD rats than in all other controls after 3 weeks on the respective diets and remained lower for the remainder of the experiment.

Absorption↗
PubMed1986

Effects of combined riboflavin and iron deficiency on the hematological status and tissue iron concentrations of the rat.

Interactions of riboflavin and iron deficiencies on utilization and storage of iron in the rat were investigated. Rats were fed diets deficient in iron (ID), riboflavin (RD) or iron and riboflavin (DD) for a period of 7 wk, at which time they were either killed and measurements of hematological indices and tissue iron concentration done or a further group of DD rats was supplemented with either iron, riboflavin or both nutrients for 2 wk. Growth was impaired in all deficient groups but the impairment was greatest in the DD rats. Iron depletion was associated with the greatest reductions in hematological indices and tissue iron concentrations, riboflavin depletion the least, while the combined deficiencies had intermediate effects. Riboflavin deficiency was found to have a "sparing effect" on iron status probably because the lower growth rate associated with riboflavin deficiency reduced iron requirements. Refeeding either iron alone or iron with riboflavin to the DD rats resulted in significant improvement in hematological status, but there was no significant difference in the response to either supplement. Feeding riboflavin alone to DD rats resulted in a further depression of hematological status and tissue iron concentration.

Animals↗
PubMed1986

A direct assay for pyridoxal 5'-phosphate using pig heart apo-aspartate transaminase.

The development of a simple enzymatic method for the determination of blood and plasma pyridoxal 5'-phosphate (PLP) using pig heart apo-aspartate transaminase (apo-AST) is described. The technique requires three steps: sample extraction using perchloric acid, a binding step in which PLP in the sample extract is attached to the apo-AST and the enzymatic assay of the reconstituted holo-AST. PLP extracts were analysed with and without a known concentration of added PLP to correct for variation in recovery between different specimens. Procedures are outlined for manual and automatic analysis of the PLP extracts. Using the KONE Clinical Analyser after the extraction step, it is possible to measure enzyme activity in 100 specimens (i.e. 400 tubes) in a 5 h period. Results are shown from 185 healthy women aged 20-45 years, in which plasma PLP concentrations ranged from 5 to 165 nmol/L, and 142 men and 56 women in government service aged 17-64 years, whose plasma PLP ranged from 8 to 169 nmol/L. Values less than 20 nmol/L are believed to indicate vitamin B6 deficiency and the method is able to measure 5 nmol/L.

Adolescent↗
PubMed1986

Effect of ethanol on erythrocyte acetylcholinesterase activity.

Erythrocyte acetylcholinesterase (AchE) activity was measured in the blood of 36 alcoholic subjects and 41 healthy volunteers. The mean activity in the alcoholics was significantly lower than that in the control subjects. In vitro experiments showed that ethanol inhibited the AchE activity immediately and in proportion to the concentration of ethanol used. Incubation times up to 6 h did not increase the inhibition significantly. Incubation of normal red cells with ethanol for 15 h, followed by washing, showed also that AchE activity was inhibited by the previous exposure to ethanol and that washing did not reduce the inhibitory effect. The possibility is considered that depressed erythrocyte AchE activity may be an early indication of potential disturbances of the autonomic nervous system. The importance of reporting ethanol intake in patients with organophosphorus poisoning is stressed.

Acetylcholinesterase↗
PubMed1986

The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status.

Plasma tocopherol was measured in 85 alcoholic patients and 40 control subjects from a local factory. Cholesterol, triglycerides and phospholipids were measured individually and summed to give an estimate of total serum lipids. Plasma tocopherol concentrations of the alcoholics were significantly lower than those of the controls and showed wide variation from marked deficiency to the upper limit of the normal range. Using regression analysis, 1.11 mumol tocopherol/mmol total lipids were calculated as the threshold of deficiency equivalent to 0.8 mg tocopherol/g total lipid established by Horwitt et al. The sensitivity and specificity of other tocopherol:lipid ratios for identifying vitamin E deficiency was compared with the tocopherol:total lipid ratio. Thresholds of deficiency for the different tocopherol:lipid ratios were calculated. The tocopherol:cholesterol+triglyceride ratio was found to be almost as powerful in identifying vitamin E deficiency as the tocopherol:total lipid ratio (sensitivity 95%, specificity 99%). Of the tocopherol:individual lipid ratios, the tocopherol:cholesterol ratio gave the best results (sensitivity 86%, specificity 94%).

Alcoholism↗