Search PubMed⌕ Search

Biomedical subjects

H McNulty

Publications and source records attributed to H McNulty.

At least 37 records · Page 2Linked to original sources

Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people.

Free-living elderly people aged > or = 65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vitamin B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low-dose riboflavin supplementation improved status of the limiting nutrient significantly (P<0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient.

Age Factors↗

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid.

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red-cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.

Adult↗

Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects.

BACKGROUND: Recommendations by the UK Department of Health suggest that protection from neural tube defects (NTD) can be achieved through intakes of an extra 400 microgram daily of folate/folic acid as natural food, foods fortified with folic acid, or supplements. The assumption is that all three routes of intervention would have equal effects on folate status. METHODS: We assessed the effectiveness of these suggested routes of intervention in optimising folate status. 62 women were recruited from the University staff and students to take part in a 3-month intervention study. Participants were randomly assigned to one of the following five groups: folic acid supplement (400 microgram/day; I); folic-acid-fortified foods (an additional 400 microgram/day; II); dietary folate (an additional 400 microgram/day; III); dietary advice (IV), and control (V). Responses to intervention were assessed as changes in red-cell folate between pre-intervention and post-intervention values. FINDINGS: 41 women completed the intervention study. Red-cell folate concentrations increased significantly over the 3 months in the groups taking folic acid supplements (group I) or food fortified with folic acid (group II) only (p<0.01 for both groups). By contrast, although aggressive intervention with dietary folate (group III) or dietary advice (group IV) significantly increased intake of food folate (p<0.001 and p<0.05, respectively), there was no significant change in folate status. INTERPRETATION: We have shown that compared with supplements and fortified food, consumption of extra folate as natural food folate is relatively ineffective at increasing folate status. We believe that advice to women to consume folate-rich foods as a means to optimise folate status is misleading.

Adolescent↗

Nutrient intakes and impact of fortified breakfast cereals in schoolchildren.

OBJECTIVE: To report micronutrient intakes in Northern Ireland schoolchildren, and to establish the contribution of fortified breakfast cereal to overall nutrient intakes and achievement of current dietary recommendations. DESIGN: Analysis of dietary intakes and physical characteristics of participants in a randomly selected 2% population sample of 1015 schoolchildren aged 12 and 15 years in Northern Ireland during the 1990/1 school year. MAIN OUTCOME MEASURES: Dietary intakes, physical characteristics, and their association with consumption of fortified breakfast cereal. RESULTS: Mean micronutrient intakes were generally adequate with the exception of low intakes of folate (boys and girls) and iron (girls). Fortified breakfast cereals, consumed by a high proportion (94% boys; 83% girls) of the sample, were associated with higher daily intakes of most micronutrients and fibre and with a macronutrient profile consistent with current nutritional recommendations. Appreciable proportions of subjects who did not consume fortified breakfast cereals had daily intakes that fell below the lower reference nutrient intake for riboflavin, niacin, folate, vitamin B-12, and iron (girls). CONCLUSIONS: The results demonstrate the potential of fortification in contributing to micronutrient intakes of schoolchildren, particularly where requirements are high, or for those on marginal diets of low nutritional quality.

Adolescent↗

The Measles/Rubella Immunisation Campaign in Greater Glasgow: a success in collaboration.

The recent UK campaign to immunise schoolchildren against measles and rubella involved, in Greater Glasgow, about 143,000 schoolchildren attending 300 primary, 63 secondary and 54 special schools administered by Strathclyde Regional Council and 21 private schools. The campaign involved a large number of individuals and professional groups, both in education and the health service. Despite-or perhaps because of-the magnitude and complexity of the task, and the very short time available, the campaign was planned and brought to a successful conclusion with a quite remarkable degree of enthusiasm and goodwill. As a result it was possible to immunise 88% of eligible schoolchildren in an area which has 46% of its population living in the most deprived postcode sectors (Carstairs categories 6 and 7) and to record all results on computer file as a permanent and readily accessible record. The campaign provided an unusual opportunity to demonstrate how effectively different organisations within the health service can collaborate with one another and with other agencies when there is a clear goal and deadline imposed.

Adolescent↗

Folate catabolism is related to growth rate in weanling rats.

The relationship between growth rate and folate catabolism was determined using a catch-up growth model in weanling rats. A recently developed HPLC method was employed to compare the urinary excretion of the major end product of folate catabolism, acetamidobenzoylglutamate (apABGlu), in normally growing (n = 8) and age-matched growth-restricted (n = 8) weanling animals, during and after food restriction. During the 12-d period of food restriction in which restricted rats were fed (per gram of body weight) at a level of 50% of the required dietary intake for normal growth, apABGlu excretion was significantly higher in normally growing rats compared with growth-restricted rats. In the latter group after restriction, apABGlu concentrations increased markedly, tending to exceed those of normally growing rats of comparable age. Thus growth retardation resulted in a decreased rate of folate catabolism, whereas accelerated growth following dietary restriction was associated with an increase in catabolism. Because early growth in rats is predominantly hyperplastic, these results suggest that the rate of folate catabolism is related to folate utilization in cell division.

4-Aminobenzoic Acid↗

Folate requirements for health in different population groups.

Folate coenzymes are required for the transfer and utilisation of one-carbon units in essential reactions involving amino acid metabolism, and the synthesis of purines and pyrimidines. Much of our understanding of human folate requirement comes from the study of folate deficiency, as it progresses from early haematological changes to eventual clinical manifestations. In population studies folate status may be assessed during the early stages of negative balance, before functional and clinical changes occur, by means of both dietary evaluation and biochemical measurements. Sub-optimal folate status may arise as a result of a number of environmental, physiological or pathological factors which cause decreased availability, increased requirement, or both. Current reference values for folate apply to intakes in healthy population groups. New recommendations for folic acid in the prevention of both first occurrence and recurrence of neural tube defects have recently been published. Folate nutrition may also have a role in coronary heart disease and various cancers.

Adolescent↗

Reversed-phase high-performance liquid chromatographic method for the quantitation of endogenous folate catabolites in rat urine.

We describe a reversed-phase high-performance liquid chromatographic procedure for the analysis of rat urine for p-aminobenzoylglutamate (pABGlu) and its acetamido derivative (p-acetamidobenzoylglutamate, apABGlu). These two catabolites arise following the in vivo cleavage of the folate molecule at the C-9-N-10 bond. Known quantities of high-specific-activity tritiated forms of the catabolites are added as internal standards to aliquots of rat urine. Following preliminary sample clean-up on C18 Sep-Pak cartridges, including derivatisation in the case of pABGlu, the urinary extracts are quantitated by HPLC. The present assay makes possible for the first time the determination of endogenous folate breakdown in the rat.

4-Aminobenzoic Acid↗

Folate catabolism is increased during pregnancy in rats.

The hypothesis examined in the present study is that pregnancy results in a greater rate of folate catabolism. Mammalian folate catabolism proceeds by cleavage of the vitamin at the C9-N10 position to yield p-aminobenzoylglutamate, which is quantitatively excreted in the urine after its acetylation. A recently developed HPLC method for the determination of endogenous levels of this catabolite, acetamidobenzoylglutamate, in rat urine was used to investigate folate catabolism in three groups of female rats (n = 6/group), one nonpregnant and two pregnant groups. One of the pregnant groups was allowed to feed freely whereas the other was pair-fed to the nonpregnant control group. The daily excretion of acetamidobenzoylglutamate was stable in the nonpregnant group over the experimental period but increased significantly with progression of gestation in both pregnant groups, in which values peaked at d 18 to concentrations of up to three times those of the nonpregnant animals. In both pregnant groups the values fell significantly before parturition, demonstrating that increased catabolism of folate is a feature of pregnancy per se and not simply due to increased weight. These results suggest that increased catabolism may make an important contribution to the folate deficiency associated with pregnancy.

Animals↗

The design and construction of a central radiopharmacy.

Following an inspection by the Medicines Control Agency (MCA) of the existing radiopharmacy, it was necessary to design and build a new facility at the Western Infirmary to supply radiopharmaceuticals for patient use throughout the West of Scotland. This is one of the largest radiopharmacies in Europe, supplying some 40,000 patient doses per year prepared using both closed and open procedures. The design parameters and construction details of the new facility are presented.

Facility Design and Construction↗

The quantitative analysis of endogenous folate catabolites in human urine.

In man folates are catabolized and excreted as inactive cleaved degradation products, a mixture of pteridines and p-aminobenzoylglutamate (pABGlu) or its acetamido derivative (apABGlu). The daily rate of excretion represents the inescapable use of the vitamin in metabolic activity and thus has implications for determining the recommended dietary allowance for the vitamin. Furthermore, the rate of catabolism has been suggested to rise during pregnancy and in certain disease states. A method is described for the quantitative extraction and assay of the folate catabolites pABGlu and apABGlu in human urine. Aliquots of 24-h urine collections are acidified and applied to columns of Dowex 50W cation-exchange resin. The catabolites are selectively batch-eluted with increasing concentrations of HCl. The fraction containing pABGlu is diazotized and then applied to a C18 Sep Pak column for further purification and concentration. The fraction containing apABGlu was deacetylated and reapplied to the Dowex column and then treated identically to the pABGlu fraction. The methanolic concentrates of both extracts were evaporated to dryness and reconstituted with water and pABGlu was regenerated by reductive cleavage of the diazotized material with Zn/HCl. The extracts of the two catabolites were separated by reverse-phase HPLC using a Radial Pak C18 column. Recovery of isolated material was monitored by the addition of high specific activity tritiated labels of both compounds added as internal standards to all urine aliquots prior to purification and analysis.

4-Aminobenzoic Acid↗

Folate catabolism in normal subjects.

All official recommendations for folate tend to be far in excess of current estimated intakes. Several recent studies have highlighted this, showing satisfactory folate status in healthy populations consuming considerably less than official RDAs. This study takes a critical look at current RDAs for folate. We have recently developed an assay to quantify the end product of folate catabolism in human urine, thus affording the possibility of a more rational and scientific approach to setting the RDA for folate. Results of this study (now confirmed by further work) suggest that, under normal dietary conditions, the body appears to catabolize only about 100 micrograms total folate per day. Furthermore, this rate of catabolism remained relatively unchanged in response to saturating doses of a 5 mg folic acid supplement over several days. It is therefore most unlikely that our diet is as seriously deficient in folate as current official RDAs seem to imply.

Adult↗

Collaboration and work sharing of drug information services in the United Kingdom.

The United Kingdom Drug Information Network has been developed in recent years to form an effective service. The structure of the health service is discussed and the organization of drug information services within this framework is outlined. A number of collaborative and work sharing exercises have been undertaken between regional services and thus are reviewed together with future trends for the service.

Drug Information Services↗