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Biomedical subjects

D I Thurnham

Publications and source records attributed to D I Thurnham.

At least 37 records · Page 2Linked to original sources

Intestinal absorption of beta-carotene, lycopene and lutein in men and women following a standard meal: response curves in the triacylglycerol-rich lipoprotein fraction.

A high intake of fruit and vegetables is believed to be protective against heart disease and cancer. beta-Carotene has been closely examined for evidence of these protective properties but evidence is still conflicting and there are many other carotenoids in plant foods which deserve attention. This paper reports studies on the concentrations of lutein and lycopene in the triacylglycerol-rich lipoprotein (TRL) fraction of plasma in comparison with beta-carotene following a large dose of the respective carotenoids fed with a standard meal after an overnight fast. beta-Carotene (40 mg) was given to twelve volunteers (six men and six women) and six of the same volunteers (three men and three women) also received 31.2 mg lutein or 38 mg lycopene. Plasma was collected at hourly intervals for 8 h and the TRL fraction was separated and subsequently analysed for the respective carotenoids and retinyl palmitate in the case of beta-carotene. Intestinal uptake of the three carotenoids was estimated using the 'area under the curve' method and apparent absorption was calculated from these results. The response curves in the TRL fraction for beta-carotene and retinyl palmitate occurred maximally over the fourth to fifth hour postprandially. There was a correlation between the TRL concentrations of beta-carotene and retinyl palmitate (males r 0.62, P < 0.001; females r 0.52, P < 0.001) and there was no significant difference between men and women either in the total amount of beta-carotene appearing in the TRL fraction or in the amount converted to retinol. On estimation, approximately 1.4 mg of the 40 mg beta-carotene dose was absorbed and this was not significantly different from the amount of lycopene (1.0 mg) but significantly different (P < 0.05) from the amount of lutein (0.8 mg) absorbed, after correction for the smaller doses administered. There was approximately a twofold difference between subjects in the uptake of beta-carotene into the TRL fraction, a two- to threefold variation in lycopene and a two- to threefold variation in lutein. Despite these inter-subject differences, in three volunteers between whom there was a threefold difference in beta-carotene in the TRL fraction and a twofold difference in retinol formation, repeat experiments with beta-carotene 4 months later found differences of only 3-6% in the TRL beta-carotene content and 4-9% for the TRL retinol formed. In conclusion, large inter-subject variation in TRL carotene uptake precluded any differences between sexes but surprising intra-subject consistency was observed in TRL beta-carotene uptake of three subjects.

Adult↗

Glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities in riboflavin-deficient rats infected with Plasmodium berghei malaria.

Riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. The objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (EC 1.11.1.9; GPx) and superoxide dismutase (EC 1.15.1.1; SOD) in rats infected with Plasmodium berghei malaria. Riboflavin in its co-enzyme form, FAD, is required by glutathione reductase (EC 1.6.4.1) to regenerate GSH and GSH is an important cellular antioxidant both in its own right and also as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for 8 weeks before intraperitoneal injection of 1 x 10(6) P. berghei parasites. Control animals were weight-matched to the respective riboflavin-deficient group. At 10 d post-infection, parasite counts were higher in the weight-matched control group than the riboflavin-deficient group (P = 0.004). GPx activity was higher in erythrocytes of rats parasitized with P. berghei than comparable non-infected rats regardless of riboflavin status (P < 0.05). As mature erythrocytes do not synthesize new protein, the higher GPx activities were probably due to the presence of the parasite protein. In erythrocytes from riboflavin-deficient rats, GPx activity tended to be lower than in those rats fed on diets adequate in riboflavin (weight-matched controls) whether parasitized or not, but the difference was not significant. Neither riboflavin deficiency nor malaria had any effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency has no marked effect on erythrocyte GPx or SOD activity in the rat.

Animals↗

Impact of health service provision on mothers and infants in a rural village in North West Frontier Province, Pakistan.

OBJECTIVE: The objective of this paper is to examine the impact of the Health Service Research Project of the Pakistan Medical Research Council (PMRC) on mothers and infants in Budhni village, North West Frontier Province (NWFP), Pakistan. METHODS: Information from the PMRC records on the socioeconomic and demographic situation over the last 10 years and anthropometric measurements made on all infants from 1986-96 were collected and analysed. RESULTS: The demographic data showed a number of changes, namely a reduction in birth rate and improvements in perinatal, neonatal, infant and child mortality rates. Literacy in the village was poor (27 and 39% literate in 1986 and 1996, respectively) and female literacy showed no improvement (14%). Improvements in sanitation and in the water supply introduced by the PMRC had limited success, as clean water was subsequently contaminated by unclean hands and utensils, and 50% of the population continued to use open fields for sanitation. In 1986 only 27% of children 0-5 years were vaccinated, but by 1996, 96% of children had completed polio, diphtheria/pertussis/tetanus (DPT) and bacille Calmette-Guérin (BCG) vaccination programmes and 95% of women of child-bearing age were vaccinated against tetanus. Protection against tetanus reduced neonatal deaths and from 1993 onwards there have been no further cases. Anthropometric data for the period 1986-96 for infants (0-24 months) showed that at birth the majority of infants were close to the 50th National Centre for Health Statistics (NCHS) centile for weight and length, and only 5% of birth-weights were less than 2.5 kg. Growth charts showed faltering in length and weight and by 24-months length in both boys and girls was below the 3rd NCHS centile and weights were just above. CONCLUSIONS: Reductions in child mortality have occurred over the period 1986-96. However, the slow progress in adopting hygienic practices, despite health education, and the low literacy rates, particularly in women, may hamper continued improvement.

Adolescent↗

Effect of increased fruit and vegetable intake on the susceptibility of lipoprotein to oxidation in smokers.

OBJECTIVE: To evaluate the effect of an increased dietary intake of fruit and vegetables on susceptibility of LDL to oxidation in smokers and nonsmokers. DESIGN: A descriptive and prospective study. SETTING: Joseph Fourier University, Grenoble. SUBJECTS: Volunteers were age and sex matched in the smoking and nonsmoking groups and were recruited by announcement. INTERVENTIONS: Increased intake of fruits and vegetables for two weeks providing 30 mg/day of carotenoids. MAIN OUTCOME MEASURES: Circulating levels of beta-carotene, lutein, lycopene, alpha-tocopherol; susceptibility of LDL to oxidation. Cu-Zn superoxide dismutase (Cu-Zn SOD), and Se glutathione peroxidase (Se-GSH-Px) activities and reduced (GSH) and oxidized (GSSG) glutathione. RESULTS: At entry (week 0: W0) smokers exhibited a lower plasma carotene level but the plasma parameters of oxidative stress and LDL oxidizability were not different from nonsmokers. After two weeks of increased intake of fruits and vegetables the circulating levels of carotenoids increased in smokers 23% and 11% in nonsmokers. At the same time the resistance of LDL to oxidation increased by 14% in smokers (P < or = 0.05) and by 28% in nonsmokers (P < or = 0.025). The mean whole blood GSH level was higher in smokers at entry but returned to a concentration similar to nonsmokers at the end of the study. CONCLUSION: This pilot study indicates that an increased, carotenoid rich food intake through its inhibitory effect on the susceptibility of LDL to oxidation may be an interesting approach to reduce the risk of atherosclerosis both in smokers and nonsmokers.

Adult↗

Influence of malaria on markers of iron status in children: implications for interpreting iron status in malaria-endemic communities.

To investigate Fe nutritional indices in malaria infection in children, haematology (blood haemoglobin, plasma ferritin, transferrin, Fe, and transferrin saturation), acute phase markers (albumin and caeruloplasmin) and liver function tests were studied in fifty consecutive cases of severe and mild falciparum malaria, fifty matched controls and twenty-three cases of asymptomatic malaria. Blood haemoglobin and transferrin were lower, while ferritin and transferrin saturation were higher, in groups with symptomatic malaria in comparison with the control group. The differences were greatest with the severest form of the disease. There were no differences between any of the groups in plasma Fe. Plasma transferrin correlated directly with albumin in asymptomatic, mild and severe malaria groups (r 0.48, 0.65 and 0.83; P < 0.05, P < 0.05, P < 0.01 and P < 0.001 respectively), and inversely with caeruloplasmin (r -0.65, -0.34 and -0.43; P < 0.01, P < 0.05 and P < 0.01 respectively). For ferritin, the correlation was inverse with albumin (r -0.65, -0.57 and -0.64; P < 0.01, P < 0.001 and P < 0.001 respectively and direct with caeruloplasmin (r 0.83, 0.21 and 0.49, P < 0.001, NS and P < 0.001 respectively). Multiple regression analysis on data from all patients combined indicated that albumin, and to a lesser extent alanine aminotransferase (EC 2.6.1.2) activity, explained 62 % of the variance in transferrin. Caeruloplasmin, parasite count and albumin explained 59 % of the variance in ferritin, and transferrin and unconjugated bilirubin explained 62 % of the variance in Fe values. In conclusion, these data suggest that low transferrin and high ferritin values are primarily due to the acute phase response. High transferrin saturation and lack of differences in plasma Fe between the groups are probably due to Fe released from lysed erythrocytes. Finally, in both symptomatic and asymptomatic malaria, indices of Fe status can be misleading and may be especially problematic in community studies in malaria-endemic areas where asymptomatic malaria may be common.

Acute Disease↗

The possible significance of parallel changes in plasma lutein and retinol in Pakistani infants during the summer season.

Recent evidence suggests that plasma lutein is better correlated than either beta-carotene or lycopene with its respective carotenoid intake and therefore may be a better marker of vegetable intake than either beta-carotene or lycopene. In the study reported in this paper, measurements of plasma carotenes and retinol were made in infants from two villages near Peshawar in the North West Frontier Province, Pakistan, in July and November 1993. The approximate age at the start was 14 months, and 101 boys and ninety girls completed the study. Of the usual plasma carotenes, only lutein was measurable in all samples and was correlated with retinol in both boys (r 0.38, P < 0.0001; r 0.35, P < 0.001) and girls (r 0.21, P = 0.038; r 0.0307, P = 0.003) at the two time points respectively. In addition, the change in lutein was even more strongly correlated with the change in retinol in both boys (r 0.453, P < 0.0001) and girls (r 0.439, P < 0.0001). In August beta-carotene was measurable in approximately 8 % of samples and this increased to 31 % in November but there was no correlation between beta-carotene and retinol at any time. There were negligible amounts of lycopene and beta-cryptoxanthin in plasma at both time points. The mean concentration of plasma retinol in the infants was 0.66 mumol/l at baseline and 59% of the infants had retinol concentrations < 0.7 mumol/l. In addition, there were fifteen infants whose levels were below 0.35 mumol/l suggesting that vitamin A status in the population was marginal. Food intake of the infants was not monitored in the present study but breast feeding continues for up to 2 years in this part of Pakistan and most infants would be weaned onto selected foods eaten by the family. The close correlation between plasma lutein and retinol suggests that the increase in retinol over the summer season may be attributable to an increased availability of green vegetables to the families. The source of lutein to the infants is most likely to be the breast milk since such vegetables are unlikely to be given to infants except to suck as a weaning food. The results may indicate the potential usefulness of plasma lutein as a marker of changes in vegetable intake and changes in vitamin A status in Third World infants and children.

Biomarkers↗

Comparative effects of malaria and malnutrition on plasma concentrations of antioxidant micronutrients in children.

The comparative effects of malaria and malnutrition on plasma antioxidant vitamins were studied in 65 children aged 8-96 months. Forty-six (71%) of them had malaria; nineteen (29%) served as controls. Patients and controls were further subdivided into two groups depending on whether they were malnourished or well nourished, as defined by weight-for-age Z score (WAZ) +/- -2. Plasma levels of alpha-tocopherol, beta-carotene and retinol were measured. Results indicate that malaria was associated with levels of antioxidants lower than in the controls. Two-way analysis of variance shows that for all three plasma micronutrients concentrations were lower in those children infected with malaria but were not influenced by malnutrition. There were an equal number of malnourished children in both malaria and non-malaria groups; nevertheless, WAZ tended to be lower in those with malaria (p = 0.056), although this did not quite reach significance. It is concluded that in areas where malaria and malnutrition co-exist, malaria alone exerts a greater influence on plasma antioxidants than does malnutrition.

Antioxidants↗

Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers.

BACKGROUND: In the UK EPIC validation studies, the accuracy of several methods was assessed by comparison with to-day weighed records and the biomarkers, 24-hour urine nitrogen (N) and potassium (K), plasma carotenoids and plasma vitamin C. METHODS: Comparisons between methods were made on 156 women, studied over 1 year at 3-monthly intervals at home. On each of four occasions, volunteers completed 4 days of weighed records and provided two 24-hour urine collections and a fasting blood sample. RESULTS: In comparison with the 16 days of weighed records, a food frequency questionnaire (FFQ) yielded higher values mainly due to greater reported consumption of milk and of vegetables. A 24-hour recall was as good as the FFQ in placing individuals in the distribution of habitual diet from weighed records. Results obtained from a 7-day estimated record were closest to those obtained from the weighed record. Correlations between 24-hour urine excretion and dietary N intake from weighed records were high (0.78-0.87) as were those with estimated food diaries (0.60-0.70). Correlations between urine N and the FFQ and 24-hour recall were lower (0.10 to 0.27), but improved by energy adjustment using residuals for N and K which are correlated with total energy intake. Comparisons between dietary estimates and urinary K and serum carotenoids and vitamin C showed broadly similar results. Limited biomarker information amongst 200 UK EPIC participants supported the findings of the validation study. CONCLUSIONS: UK EPIC uses three methods (the 7-day diary, an improved FFQ, and the 24-hour recall) to assess diet. 93% of first food diaries are returned completed by participants. Repeated diaries are the main dietary assessment method for nested case-control analyses.

Aged↗

Micronutrients and immune function: some recent developments.

Micronutrient deficiencies probably have few direct effects on the functioning of immune cells. The main effect appears to be a reduction in cell mass that may indirectly affect immune cell function, particularly where T helper cell numbers are reduced. Results of many human studies are contradictory. Some of this contradiction may be accounted for by the fact that disease may lower concentrations of micronutrients in plasma that may be misinterpreted as deficiency. Low plasma vitamin A concentrations however appear to impair immune responsiveness and have deleterious effects on membrane integrity and mucosal function. Zinc may have similar effects on gut integrity and appears to be particularly useful in the treatment of acute diarrhoea. Low concentrations of other nutrients such as ascorbate and iron, may not necessarily impair immune function. Low plasma ascorbate may assist the removal of iron from plasma and low iron concentrations appear to increase the cytotoxicity of macrophages.

Acute-Phase Reaction↗

The correlation between the intake of lutein, lycopene and beta-carotene from vegetables and fruits, and blood plasma concentrations in a group of women aged 50-65 years in the UK.

The correlations between the mean of 4 d weighed intakes of lutein, lycopene and beta-carotene and mean plasma concentrations during each of the four seasons were lutein r 0.64, lycopene r 0.47 and beta-carotene r 0.45. Intake was not significantly correlated with plasma concentrations during every seasonal time-point. There was a significantly higher intake of lutein during the spring compared with summer and autumn, lycopene intake was significantly higher during the summer and autumn and there were no significant seasonal differences in beta-carotene intake. There were, however, significant seasonal differences in plasma carotenoid concentrations, the highest levels occurring between May and October. There were large inter- and intra-individual variations in intake and plasma concentrations of carotenoids. BMI was inversely correlated with plasma beta-carotene (r-0.41). The findings suggest that plasma carotenoid concentrations are indicative of dietary intake, but the large intra-individual variation in plasma concentrations indicates that any assessment of longer-term status from data at any one time-point should be treated with caution.

Aged↗

Plasma alpha-tocopherol, retinol, and carotenoids in children with falciparum malaria.

Cross-sectional interactions by malaria status were investigated between plasma alpha-tocopherol, retinol, and several carotenoids (lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene) and indicators of disease severity (blood parasite count, hemoglobin concentration), acute-phase response (plasma albumin and ceruloplasmin concentrations), hepatic involvement (plasma alanine aminotransferase), oxidant status and antioxidant status (plasma thiobarbituric acid-reactive material and ascorbate), nutritional (weight-for-age) and carrier protein [retinol binding protein (RBP)] status, and cholesterol concentration (as a proxy for lipoprotein) in 100 consecutively admitted children with malaria. There were 50 children with severe and 50 with mild malaria and 50 age- and sex-matched control subjects. alpha-Tocopherol, retinol, and all the carotenoid concentrations were lower in the patients than in the control subjects (P < 0.001). The differences were greater in severe than in mild malaria, except for lutein. In severe malaria only, both retinol and alpha-tocopherol correlated with albumin, ceruloplasmin, and RBP concentrations whereas in all three groups retinol correlated with RBP and alpha-tocopherol correlated with cholesterol (all P < 0.01)). Using multivariate analysis on data from all patients combined, cholesterol was the most significant factor explaining the variance in alpha-tocopherol (29%) whereas RBP was responsible for 95% of the variance in retinol. Plasma cholesterol and RBP values in turn (in the absence of alpha-tocopherol and retinol, respectively) were influenced primarily by acute-phase markers (mainly albumin and ceruloplasmin). Alanine aminotransferase (r = -0.17) and thiobarbituric acid-reactive material (r = -0.17) also showed a small contribution to the variance of RBP but 60-70% remained unexplained. In conclusion, low plasma lipid-soluble micronutrient concentrations in malaria are strongly influenced by the reductions in their carrier molecules, which, in turn, are low as a consequence of the acute-phase response.

Carotenoids↗

Effect of improved vitamin A status on response to iron supplementation in Pakistani infants.

We report an apparently protective effect of vitamin A in infants who received iron supplements (15 mg/d) for 3 mo. Those receiving iron showed increases in hemoglobin (8 g/L), ferritin (3.7 micrograms/L), and the acute-phase protein alpha 1-antichymotrypsin (ACT; 0.06 g/L). In both the placebo and iron-supplemented groups there were increases in plasma retinol, lutein, alpha-tocopherol, immunoglobulin A, and immunoglobulin G. The improvement in vitamin A status could only have been from a seasonal increase in dietary sources of vitamin A, eg, breast milk and early weaning foods, and there were no obvious effects on iron utilization (hemoglobin concentrations). However, in the infants receiving iron, those whose retinol concentrations increased also showed reductions in ACT, ferritin, immunoglobulin A, and immunoglobulin M. Vitamin A is well known for its antiinfective properties and we suggest that these observations illustrate the importance of even small increases in dietary vitamin A or differences in vitamin A status in reducing the potentially toxic effects of iron supplements in persons in developing countries. These conclusions should now be confirmed with an intervention study to show that the benefits of vitamin A on iron status are due to reduced levels of infection.

Acute-Phase Proteins↗

Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.

OBJECTIVE: To measure erythrocyte glutathione reductase (EGR) activity and riboflavin status, and their relations to disease activity, in rheumatoid arthritis patients compared to healthy controls. METHODS: Patients with rheumatoid arthritis were classified as active if there were features of articular inflammation which required initiation or change of disease modifying therapy, and as inactive if they had little evidence of articular inflammation. EGR was measured in patients and healthy controls by a functional assay with or without the addition of flavin adenine dinucleotide (FAD). The ratio of stimulated EGR (with FAD added) to basal EGR (no added FAD), which measures riboflavin status, is known as the EGR activation coefficient (EGRAC). An EGRAC > or = 1.3 represents biochemical riboflavin deficiency. RESULTS: 91 patients with rheumatoid arthritis, including 57 with active disease, and 220 healthy controls were studied. Both basal and stimulated EGR were significantly higher in patients with rheumatoid arthritis (P = 0.0001) than in controls. Biochemical riboflavin deficiency was identified in 41% controls and 33% patients with active rheumatoid arthritis but was significantly less frequent (9%) in patients with inactive compared to active disease (P = 0.02) or healthy controls (P = 0.0006). Pain score, articular index, C reactive protein, and erythrocyte sedimentation rate were increased in patients with riboflavin deficiency (all P < 0.02). CONCLUSIONS: Higher basal and stimulated EGR might be expected in patients with rheumatoid arthritis in response to chronic oxidative stress due to synovial inflammation. The association of riboflavin deficiency with increased disease activity suggests that impaired EGR activity could facilitate continuing inflammation in these patients.

Adult↗

Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.

High intakes of antioxidants in fruit, vegetables and wine are thought to protect against coronary heart disease (CHD). Because people in Toulouse have a much lower incidence of CHD compared with Belfast, the plasma concentrations of antioxidant vitamins and carotenoids in the two populations have been compared. The major difference was in some of the plasma carotenoids. Hydroxy-carotenoids were twice as high in Toulouse in both sexes, notably lutein which occurs principally in dark green vegetables and beta-cryptoxanthin which occurs chiefly in citrus fruits. In addition, alpha-carotene was 50% higher in Toulouse, gamma-tocopherol was 50% higher in Belfast. Other plasma vitamins and carotenoids were not significantly different. If antioxidants play a role in preventing CHD, then the hydroxy-carotenoids are major candidates for further investigation.

Aged↗

Stability of vitamins A, C, and E, carotenoids, lipids, and testosterone in whole blood stored at 4 degrees C for 6 and 24 hours before separation of serum and plasma.

To investigate whether overnight storage causes significant changes in whole blood, we measured serum and plasma concentrations of vitamins A, C, and E, carotenoids, lipids, and testosterone in whole blood samples stored in a refrigerator at 4 degrees C for 6 and 24 h before centrifugation, aliquoting and freezing them at -70 degrees C or below. In comparison with baseline samples prepared within 2 h, the mean percentage changes at 24 h were: -3.0% to +1.0% for retinol, alpha-tocopherol, and gamma-tocopherol in plasma; -8.7% to -0.1% for carotenoids in plasma; -7.2% for vitamin C in plasma and -1.8% for vitamin C in serum; -2.7% to +2.4% for lipids in serum; and +0.4% to +6.2% for testosterone in serum and plasma from men and women. Spearman's rank correlation coefficients between measurements made in the baseline samples and those made after storage for 24 h were greater than 0.9 for 11 analytes, between 0.8 and 0.9 for 7 analytes, and less than 0.8 for only 1 analyte (vitamin C in serum). The ratio of between-subject to within-subject coefficients of variation was greater than 3.0 for all analytes except lutein (ratio, 1.6), alpha-cryptoxanthin (ratio, 2.4) and vitamin C (ratio in serum, 3.0; ratio in plasma, 2.2). We conclude that storage of whole blood at 4 degrees C for 24 h before freezing does not cause important changes in the analytes studied and that this delay in processing may be incorporated in the design of large prospective studies.

Ascorbic Acid↗