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Biomedical subjects

D A Bender

Publications and source records attributed to D A Bender.

At least 19 recordsLinked to original sources
PubMed2003

Do we really know vitamin and mineral requirements for infants and children?

Infants and young children require vitamins and minerals not only to replace losses through metabolic turnover, but also to increase body reserves as they grow. For infants up to six months of age it is generally assumed that breast milk provides adequate intakes, and average breast milk composition provides the basis of reference intakes for this age group, and the basis for infant formula. It is questionable to what extent the micronutrient content of breast milk reflects the infant's requirements as opposed to the mother's nutritional status. For obvious ethical reasons there have been very few (if any) experiments to determine the micronutrient requirements of infants and children, although studies of intakes in areas where deficiency is common provide an estimate of minimum requirements in some cases. Different national and international authorities have approached the problem of estimating reference intakes for infants and young children in four main ways: linear interpolation between adequate intakes estimated from breast milk composition and the experimentally-determined requirements of young adults; extrapolation forwards from breast milk composition and backwards from the requirements of young adults on the basis of metabolic body weight (body weight0.75), corrected by growth factors; extrapolation backwards from the requirements of young adults on the basis of the energy density of the diet; and by factorial calculation. Despite this, there is considerable concordance between the figures published by different authorities as a result of rounding off to avoid spurious precision.

Adolescent↗
PubMed1999

Optimum nutrition: thiamin, biotin and pantothenate.

The metabolism of glucose is deranged in thiamin deficiency, but once any deficiency has been corrected there is no further effect of increased thiamin intake on the ability to metabolize glucose through either pyruvate dehydrogenase (EC 1.2.4.1) and the citric acid cycle, or the pentose phosphate pathway, in which transketolase (EC 2.2.1.1) is the thiamin-dependent step. It has been suggested that the Wernicke-Korsakoff syndrome is associated with a genetic variant of transketolase which requires a higher than normal concentration of thiamin diphosphate for activity. This finding would suggest that there may be a group of the population who have a higher than average requirement for thiamin, but the evidence is not convincing. There are no estimates of biotin requirements, but either coenzyme saturation of erythrocyte pyruvate carboxylase, or the excretion of 3-hydroxy-isovalerate (perhaps after a test dose of leucine) could be used to assess requirements in depletion-repletion studies. Biotin deficiency leads to impaired glucose tolerance, but it is unlikely that glucose tolerance could be used to assess optimum biotin status, since other more common factors affect glucose tolerance to a greater extent. Plasma triacylglycerol and nonesterified fatty acids are moderately elevated in pantothenic acid deficiency. However, this is unlikely to be useful in assessing pantothenate status, since again, other more common factors affect plasma lipids. To date there are no biochemical indices of adequate pantothenate nutrition, and no estimates of requirements.

Biotin↗
PubMed1999

Non-nutritional uses of vitamin B6.

Vitamin B6 is a water-soluble vitamin, and is readily metabolized and excreted, so it has generally been assumed to have negligible toxicity, although at very high levels of intake it can cause peripheral nerve damage. Nutritional deficiency disease is extremely rare, although a significant proportion of the population shows biochemical evidence of inadequate status, despite apparently adequate levels of intake. The vitamin has been used to treat a wide variety of conditions, which may or may not be related to inadequate intake. In some conditions use of vitamin B6 supplements has been purely empirical; in other conditions there is a reasonable physiological or metabolic mechanism to explain why supplements of the vitamin many times greater than average requirements may have therapeutic uses. However, even in such conditions there is little evidence of efficacy from properly conducted controlled trials.

Animals↗
PubMed1998

Nonpoint sources of volatile organic compounds in urban areas-relative importance of land surfaces and air.

Volatile organic compounds (VOCs) commonly detected in urban waters across the United States include gasoline-related compounds (e.g. toluene, xylene) and chlorinated compounds (e.g. chloroform, tetrachloroethane [PCE], trichloroethene [TCE]). Statistical analysis of observational data and results of modeling the partitioning of VOCs between air and water suggest that urban land surfaces are the primary nonpoint source of most VOCs. Urban air is a secondary nonpoint source, but could be an important source of the gasoline oxygenate methyl-tert butyl ether (MTBE). Surface waters in urban areas would most effectively be protected by controlling land-surface sources.

Journal Article↗
PubMed1992

Estimation of irrigant absorption during transurethral resection of the prostate. Assessment of fluorescein as a marker.

Absorption of irrigating solution may complicate transurethral resection of the prostate (TURP), and a system which warns of fluid overload reliably would be of benefit in the prevention of these complications. Fluorescein can easily be detected at very low concentrations in blood and can be added to the irrigating solution in amounts invisible to the naked eye, providing a possible means of easily monitoring the absorption of irrigant solution during TURP. To test this hypothesis, the plasma concentration of fluorescein was determined at intervals after intraperitoneal injection in rats. Although the published data on fluorescein suggest that it meets the criteria for a suitable marker substance to be introduced into the irrigant solution, the results show that plasma fluorescein is constant and not dose related. The addition of fluorescein to the irrigant solution would not provide a quantitative means of determining the volume of irrigant absorbed. The use of other substances may provide the answer to this major clinical problem. We have defined a set of criteria which such a substance should fulfil.

Absorption↗
PubMed1992

Tryptophan metabolism and vitamin B6 nutritional status in patients with schistosomiasis mansoni and in infected mice.

Patients infected with Schistosoma mansoni showed an abnormal response to a test dose of tryptophan, with little increase in the urinary excretion of kynurenine, hydroxykynurenine, xanthurenic and kynurenic acids, N1-methyl nicotinamide, methyl pyridone carboxamide, 5-hydroxytryptamine or 5-hydroxyindoleacetic acid. In contrast to previous reports, this is different from the pattern of tryptophan metabolism seen in vitamin B6 deficiency. Furthermore, the patients' plasma concentrations of pyridoxal phosphate were within the reference range, and supplementation for 5 days with 20 mg vitamin B6/day did not affect tryptophan metabolism. Treatment with a single dose of Praziquantel resulted in a substantial restoration of normal tryptophan metabolism. In mice infected with S. mansoni there was a similar impairment of tryptophan metabolism, as shown by considerably reduced formation of 14CO2 after the administration of a tracer dose of [14C]tryptophan. Again, the administration of vitamin B6 supplements did not correct tryptophan metabolism in the mice. Treatment with Praziquantel resulted in substantial restoration of the production of 14CO2 from [14C]tryptophan. There was no evidence of vitamin B6 deficiency (as determined by erythrocyte aspartate aminotransferase activation coefficient) associated with infection in the mice, although there was a redistribution of pyridoxal phosphate between tissues, with a reduction in the concentration of liver, spleen and kidney, and an increase in skeletal muscle.

Adolescent↗
PubMed1991

Pellagra with colitis due to a defect in tryptophan metabolism.

A 9-year-old girl presented with a red scaly rash confined to sun-exposed areas which started at 2 years of age and had the appearance of pellagra. Investigation of urinary tryptophan metabolites following an oral tryptophan load, showed increased excretion of kynurenine and kynurenic acid but reduced excretion of 3-hydroxy-kynurenine, xanthurenic acid and N1-methyl nicotinamide. These results indicated a defect in the hydroxylation of kynurenine, an important reaction in the synthesis of the nicotinamide nucleotide coenzymes, NAD and NADP, from tryptophan. The patient went on to develop severe colitis and psychological changes. All her symptoms responded to treatment with nicotinamide.

Child↗
PubMed1990

Schistosoma mansoni: effects on tryptophan metabolism in mice.

In mice, infection with 20-30 cercariae of Schistosoma mansoni resulted in a considerable reduction in the formation of 14CO2 from [14C]tryptophan. Infected animals excreted significantly lower amounts of kynurenine, kynurenic acid, and methyl pyridone carboxamide than did uninfected controls. There was no difference in the ability of hepatocytes isolated from infected or control animals to metabolise [14C]tryptophan. Hepatocytes from infected animals synthesized less NAD(P), but more niacin and N1-methyl nicotinamide from tryptophan. They showed no greater accumulation of kynurenine metabolites than did cells from control animals. The hepatocyte content of pyridoxal phosphate and the erythrocyte aspartate aminotransferase activation coefficient were the same in both groups of mice, suggesting that infection with S. mansoni does not deplete vitamin B6. The impairment of tryptophan metabolism in vivo was apparently not due to impaired hepatic metabolism. Rather, it seems likely that the parasites or their eggs take up tryptophan avidly from the host's circulation. Studies of parasite and egg metabolism of tryptophan may suggest novel approaches to the chemotherapy of bilharzia.

Animals↗
PubMed1990

Tryptophan metabolism in vitamin B6-deficient mice.

Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B6/kg. After intraperitoneal injection of [14C]tryptophan, vitamin B6-deficient mice showed lower liberation of 14CO2 from [methylene-14C]tryptophan and [U-14C]tryptophan than did controls, indicating impairment of kynureninase (EC 3.7.1.3) activity. There was no difference between the two groups of animals in the metabolism of [ring-2-14C]tryptophan. Hepatocytes isolated from the vitamin B6-deficient animals formed more 3-hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin.

Alanine↗
PubMed1989

Dietary intake and clinical, anthropometric and biochemical indices of malnutrition in elderly demented patients and non-demented subjects.

Anthropometric and biochemical indices of nutritional status and weighed dietary intake have been studied in hospitalized patients with senile dementia, demented patients living in the community and age-matched control subjects who were not cognitively impaired. Demented patients were lighter than control subjects, and had a lower body mass index, skinfold thickness, mid-arm circumference and arm muscle bulk. The hospitalized patients were more seriously affected than those living in the community, and body weight was significantly negatively correlated with duration of hospitalization. Over a 6-month period the hospitalized patients showed a further weight loss, while those living in the community did not. Both groups of demented patients had higher intakes of energy, protein, vitamins and minerals than the control subjects. The diet of the hospitalized patients was slightly, but not significantly, superior to that of the patients living in the community. Biochemical evidence of specific vitamin inadequacy was equally prevalent in all three groups of subjects, and there were no significant correlations between the degree of cognitive impairment or behavioural disorder and any of the indices of nutritional state. Clinical signs suggestive of malnutrition were not correlated with either biochemical evidence of deficiency or cognitive impairment and behavioural disturbance.

Aged↗
PubMed1989

Brain glutamate and gamma-aminobutyrate (GABA) metabolism in thiamin-deficient rats.

The brain metabolism of glutamate and gamma-aminobutyrate (GABA) was investigated in thiamin-deficient and pair-fed control rats, in order to determine whether the GABA shunt may provide an important alternative to 2-oxo-glutarate dehydrogenase (EC 1.2.4.2) in energy-yielding metabolism in thiamin deficiency. Brains from thiamin-deficient animals contained less glutamate, 2-oxo-glutarate and GABA than those from control animals. The brain content of ATP was unaffected by thiamin deficiency. After intracerebroventricular injection of [14C]glutamate, the specific radioactivity of GABA in the brains from deficient animals was 45-50% higher than that in controls, suggesting a considerable increase in the metabolic flux through the GABA shunt in thiamin deficiency. Brain GABA showed a marked circumannual variation, with a peak in mid-summer and a minimum value in mid-winter.

Animals↗
PubMed1989

Effects of vitamin B6 deficiency and repletion on the uptake of steroid hormones into uterus slices and isolated liver cells of rats.

1. In vitro, pyridoxal phosphate extracts steroid-hormone receptors from tight nuclear binding (Cidlowski & Thanassi, 1981); in vitamin B6-deficient rats there is increased and prolonged nuclear accumulation of oestradiol in the uterus and testosterone in the prostate, associated with enhanced biological responsiveness of these target tissues to steroid hormone action (Symes et al. 1984; Bowden et al. 1986). 2. Slices of uterus from vitamin B6-deficient rats accumulated more [3H]oestradiol than did tissue from repleted animals. Acute repletion with vitamin B6 (0.5-1 h before killing) further increased the uptake of the steroid. 3. Isolated hepatocytes from vitamin B6-deficient rats accumulated more [3H]dexamethasone than did cells from repleted animals. Pre-incubation of the hepatocytes with pyridoxal phosphate resulted in a further increase in the uptake of the steroid. 4. The results suggest that in addition to the putative role of pyridoxal phosphate in releasing steroid-hormone-receptor complexes from tight nuclear binding (Cidlowski & Thanassi, 1981), vitamin B6 deficiency may also increase the concentration of steroid-hormone receptors or enzymes and other steroid-binding proteins in target tissues.

Animals↗
PubMed1989

Effects of a dietary excess of leucine and of the addition of leucine and 2-oxo-isocaproate on the metabolism of tryptophan and niacin in isolated rat liver cells.

1. Feeding rats on a low-tryptophan, niacin-free, high-leucine diet resulted in impaired synthesis from tryptophan of the nicotinamide nucleotide coenzymes, NAD and NADP, and N1-methyl nicotinamide in isolated hepatocytes, compared with cells from animals fed on a low-tryptophan, niacin-free control diet providing an appropriate amount of leucine. This was accompanied by reduced accumulation of the tryptophan metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid. 2. With hepatocytes from animals fed on the low-tryptophan, niacin-free control diet, the addition of leucine to the incubation medium resulted in reduced synthesis of niacin from tryptophan, and a small increase in the accumulation of 3-hydroxykynurenine. 3. With hepatocytes from animals fed on the low-tryptophan, niacin-free control diet, the addition of 2-oxoisocaproate to the incubation medium resulted in increased synthesis of NAD(P) and niacin, and increased accumulation of 3-hydroxykynurenine. 4. The results suggest that a dietary excess of leucine alters the activity of the enzymes of tryptophan----niacin metabolism, or the uptake of tryptophan into the liver, in a different manner from the simple inhibition and activation seen in experiments in vitro. 5. Differences between studies in isolated hepatocytes and intact animals suggest that extra-hepatic metabolism of tryptophan, catalysed by indoleamine dioxygenase, is more important than has been believed hitherto.

Animals↗