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Biomedical subjects

A A Jackson

Publications and source records attributed to A A Jackson.

At least 19 recordsLinked to original sources

Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis.

The role of glucocorticoids in the intrauterine programming of hypertension was assessed in the progeny of rats fed either 18 g casein/100 g diet (control diet) or 9 g casein/100 g diet (low protein diet), before conception and throughout pregnancy. Rats exposed to the low protein diet had significantly (P < 0.05) higher systolic blood pressures than control animals, when weaned. These rats had elevated brain and liver activities of specific glucocorticoid-inducible marker enzymes, relative to controls. Glycerol 3-phosphate dehydrogenase activity was also higher (377%) in whole brains of newborn rats exposed to low protein diet in utero, but no similar effect of corticosteroids was noted in brains of d 20 fetuses. Weanling rats of the low protein group exhibited a blunted diurnal pattern of adrenocorticotrophin (ACTH) concentrations in plasma. Plasma corticosterone concentrations were unaltered by prenatal dietary experience and exhibited a normal pattern of diurnal variation. Brain regional 11beta-hydroxysteroid dehydrogenase activities were unaltered by prenatal dietary experience, as was binding of 3H-corticosterone to type I glucocorticoid receptors in hippocampus, hypothalamus and liver. Type II glucocorticoid receptor binding capacity and receptor numbers in male rats were apparently elevated in hippocampus of low protein-exposed rats and were significantly lower in liver (P < 0.05), relative to control rats. Programming of the hypothalamic-pituitary-adrenal axis is inferred, and the observation that binding of steroid to type II receptor sites in vascular tissue is increased in low protein exposed rats may provide a direct mechanism for modulation of blood pressure by glucocorticoids in this model.

Adrenal Glands

Protein quality and urea kinetics in prepubertal Chilean schoolboys.

Urea kinetics were measured non-invasively in 12 Chilean schoolboys aged 8-10 years who were receiving one of two diets, either predominantly animal protein or predominantly vegetable protein. Both the diets provided an equivalent level of gross protein, 1.2 g/kg/day. The study diets were given for 10 days to enable adaptation to take place. On the eighth day a single oral dose of 15N15N-urea, 100 mg, was given and the amount of label excreted as 15N15-urea in urine over the subsequent 48 hours was measured. There was little difference in any aspect of urea kinetics between the two diets with urea production (animal, 173 +/- 50 mgN/kg/day; vegetable 179 +/- 53 mgN/kg/day), urea excretion (animal, 86 +/- 19 mgN/kg/day; vegetable, 105 +/- 13 mgN/kg/day), urea nitrogen hydrolysis (animal, 87 +/- 49 mgN/kg/day; vegetable, 74 +/- 42 mgN/kg/day), and the salvaged urea-nitrogen derived from hydrolysis which returned to urea formation (animal, 12 +/- 5 mgN/kg/day; vegetable, 17 +/- 9 mgN/kg/day) all being similar. A very high proportion of the salvage nitrogen derived from urea hydrolysis was maintained within the metabolic pool, about 80%, which was equivalent to 0.4 g protein/kg/day. This is the first time urea kinetics have been measured in children of this age and shows that 57% of the ura produced is excreted in urine on average with about 43% of the urea-nitrogen being salvaged for further metabolic interaction. It is concluded that the vegetable based protein diet taken habitually by Chilean children is metabolically equivalent in terms of urea kinetics to a diet based upon animal protein at this level of intake, but that high rates of salvage of urea nitrogen are found on both diets.

Aging

Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets.

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Maternal-diet-induced hypertension has been previously associated with elevated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is investigated. Pulmonary and plasma ACE activity were determined in rats of different ages, following in utero exposure to 18 (control) or 9% (deficient) casein diets. No maternal diet induced changes in pulmonary ACE were noted, but at 4 and 13 weeks of age, plasma ACE activity was increased by 34 and 134%, respectively in 9% casein exposed rats relative to controls (P < 0.001). Thirteen-week-old rats had significantly raised systolic blood pressure (28 mmHg, P < 0.05), and tended to have higher diastolic blood pressure (not significant). These hypertensive animals had slightly raised plasma angiotensin II concentrations (30% higher, not significant), but similar renin activities, when compared with normotensive controls. Treatment of normotensive and hypertensive rats with the ACE inhibitor captopril demonstrated that higher plasma ACE activity may play a major role in the maintenance of maternal-diet-induced hypertension. Whilst normotensive rats showed no significant response to drug treatment, systolic blood pressure in the hypertensive rats fell rapidly to the level observed in the normotensive control group. Blood pressure remained at this lower level until treatment was withdrawn, at which time pressure began to increase slowly, but steadily. A period of 7-8 weeks was required following cessation of captopril administration for the restoration of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Measurement of protein turnover in normal man using the end-product method with oral [15N]glycine: comparison of single-dose and intermittent-dose regimens.

The 'single-dose end-product' approach for the measurement of protein turnover is the only method suited for application to free-living individuals and for field studies. However, the method has never been widely accepted because the results obtained appear to vary from one situation to another. There is the need for a formal comparison of the different approaches that have been used and the assumptions on which they are based in order to be able to understand the extent to which the variation in the results obtained is real or might be attributed to methodological differences. The present study used the 'prime/intermittent-dose end-product' approach over 18 h as a reference with which to compare the 'single-dose end-product' approach, with urine being collected for periods of 9 to 48 h. N flux was derived in a total of thirteen normal men using oral [15N]glycine and measurement of 15N enrichment in urinary NH3 or urea, with isotope being given either as prime/intermittent doses or a single dose in separate studies. The pattern of results was similar to those reported in the literature. In all studies the rates of N flux derived from urea were higher than those derived from NH3, under equivalent conditions, by about 25-30%. The single-dose approach, with urine collection over 9 h, gave results which were consistently higher than the prime/intermittent-dose approach. The extent of the difference was influenced by the duration of time over which the cumulative excretion of isotope in urine was determined, and with NH3 as the end-product the most consistent estimates of N flux could be obtained with a urine collection of at least 12 h and no greater than 24 h. With urea as the end-product, correction for the label retained in the body pool at 9 h gave similar results for N flux to those derived from the total excretion of label in urea over 24 h. The derivation of values for protein synthesis and protein degradation from measures of flux requires care to ensure that the time periods over which N intake and excretion are measured accord with those for which the measurement of flux apply. It is concluded that measurements of protein turnover similar to those obtained with the prime/intermittent-dose approach can be obtained with the single-dose approach in the fed state during the daytime, either from the excretion of label in urinary NH3 over a period of 12 h or with the excretion of label in urinary urea over a period of 24 h. The suitability of the method for use in the fasted state or at night time remains to be determined.

Adult

Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition.

Exposing the rat fetus to maternal low-protein diets during gestation has been shown to programme a number of metabolic and physiological changes. The present study examines the effects of maternal dietary manipulation upon glutathione cycle enzymes in the rat. Pregnant rats were fed either a non-purified chow diet or purified diets containing 18, 9 or 6% casein. Enzyme activities in the resulting offspring were determined at 4 weeks of age. Weanling pups exposed to the chow diet in utero had significantly lower activities of the glutathione synthetic enzyme gamma-glutamylcysteine synthetase in liver and lung than rats exposed to purified diets. Glutathione peroxidase activity in the liver also tended to be lower in these animals. Glutathione reductase activity in liver was negatively correlated with maternal protein intake, with rats exposed to 6% casein in utero having a significantly raised activity of this recycling enzyme, relative to controls exposed to 18% casein. These data are consistent with the hypothesis that components of maternal diet, including the level of protein intake, programme glutathione cycle enzymes, or production of their regulatory elements, in utero.

Animal Nutritional Physiological Phenomena

Altered glucose tolerance in rats exposed to maternal low protein diets in utero.

The response to an intravenous glucose load was evaluated in four groups of rats following fetal exposure to maternal diets containing 18, 12, 9 or 6% protein. The animals differed nutritionally only in terms of this prenatal experience. Animals in the 6% protein exposed group exhibited lower body weights at all ages, whilst the body weights of 9 and 12% protein exposed rats did not differ from the control group. At 9 weeks of age, a 2 g/kg body weight intravenous glucose load was cleared in 60 min by 18% protein exposed, control rats and 12% protein exposed rats. Peak blood glucose concentrations in these animals were 27.2 and 27.1 mM, respectively. Rats exposed to 9% protein in utero also cleared the glucose load in 60 min, but peak blood glucose concentrations were lower (24.4 mM), and the area under the glucose tolerance curve was 28% lower than in controls. Rats in the 6% protein exposed group cleared the glucose load in 40 min and peak blood glucose levels were only 22.1 mM. The area under the glucose tolerance curve was reduced by 40% relative to controls. When the glucose tolerance test was repeated in animals aged 44 weeks, no differences in peak glucose concentrations, area under the curve or rates of glucose clearance were observed. In utero exposure of rats to maternal low protein diets has been shown, therefore, to alter glucose tolerance in young adulthood through an, as yet, undefined mechanism.

Animals

Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets.

1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15-22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Whole body protein turnover in chronically undernourished individuals.

1. Two groups of adult men were studied in Bangalore, India, under identical conditions: the 'normal weight' subjects (mean body mass index 20.8 kg/m2) were medical students of the institute with access to habitual energy and protein intakes ad libitum. The other group, designated 'undernourished', were labourers on daily wages (mean body mass index 16.7 kg/m2). 2. In an earlier study we obtained lower absolute values for both basal metabolic rate and protein synthesis in the undernourished subjects; however, when the data were expressed on a body weight or fat-free mass basis, a trend towards higher rates of protein synthesis, as well as higher basal metabolic rate, was evident. The suggestion was made that such results reflected the relatively higher energy intakes per kg body weight of the undernourished subjects on the day of study. The objective of the present study was therefore to control for the dietary intake during the measurement of whole body protein turnover. 3. In the present study dietary intakes were equated on a body weight basis; however, expressed per kg fat-free mass, the normal weight subjects had received marginally higher intakes of energy and protein. The results, however, were similar to those of the previous study. In absolute terms, basal metabolic rate, protein synthesis and breakdown were lower in the undernourished subjects. When expressed per kg body weight or per kg fat-free mass, the undernourished subjects had higher basal metabolic rates than the well-nourished subjects, whereas no differences were seen in the rate of protein synthesis or breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The effect of acidosis on the labelling of urinary ammonia during infusion of [amide-15N]glutamine in human subjects.

In three experiments [amide-15N]glutamine was infused intravenously in male volunteers. After 4-8 h of infusion acidosis was achieved by an oral dose of CaCl2 (1 mmol/kg). In one subject acidosis was maintained for 5 d. The acid load produced an approximately 3-fold increase in urinary NH3 excretion, with a small (approximately 20%) and transient increase in the isotope abundance of urinary NH3. Estimates of glutamine production rate (flux) were obtained in two experiments. There was no evidence that it was increased in acidosis. The extra NH3 production by the kidney represented only a very small part, about 3%, of the total glutamine production rate.

Acidosis

Urea production and salvage during pregnancy in normal Jamaican women.

The pattern of aggregate nitrogen demand during pregnancy and the fetal and maternal components are unclear. Excess demand enhances efficiency of nitrogen utilization. Urea salvage contributes to enhanced efficiency. Dietary protein intake, urea production, and salvage of urea nitrogen were measured in eight nonpregnant control subjects, and trimesterly in nine pregnant women. Production was measured after prime-intermittent intravenous doses of [15N 15N]-urea by dilution of label in urinary urea. Dietary protein intake was greater in trimester 1 than in nonpregnant women (167 +/- 36 vs 224 +/- 60 mg N.kg-1.d-1), and increased further in trimester 2 (266 +/- 59 mg N.kg-1.d-1). Urea production was not higher during pregnancy. Despite higher protein intake, urea salvage was higher in pregnancy (40 +/- 24 nonpregnant vs 77 +/- 23, 61 +/- 31, and 51 +/- 12 mg N.kg-1.d-1). Therefore, the demand-supply gap for nitrogen was greatest early in pregnancy when fetoplacental growth is slowest, and implies heightened maternal demand.

Adult

The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets.

The immune system has been previously demonstrated to be under the influence of maternal nutrition in pregnancy. Assessment was made of the effects of low protein diets (12, 9 and 6 g casein/100 g diet) fed before conception and during pregnancy on the immune system of the resulting offspring in early adulthood. Control animals were fed a diet containing 18 g casein/100 g. At the end of pregnancy all dams were fed a nonpurified diet containing 18.3 g protein/100 g. Male pups were weaned onto this diet, which they consumed until the age of 7 wk. Rats exposed to 18 g casein/100 g diet in utero mounted a typical acute phase response following E. coli endotoxin challenge at age 7 wk. Food intake was 75% lower, hepatic zinc concentrations 25% greater, and serum albumin 15% lower than in saline-injected controls. Pulmonary glutathione levels were 35% greater in endotoxin-treated rats than in saline-treated controls. In rats exposed to low protein diets in utero the trend was for the acute phase response to be blunted. This was most noticeable with respect to the anorectic response, hepatic zinc uptake and pulmonary glutathione uptake. In rats not challenged with endotoxin, maternal diet had pronounced effects on tissue zinc status at the age of 7 wk. Liver zinc concentrations were 21% and 16% lower in the groups exposed to 9 and 6 g casein/100 g diets relative to the control group exposed to 18 g casein/100 g diet. Glutathione status was altered in all groups exposed to low dietary protein in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction

Maternal nutritional status in pregnancy and blood pressure in childhood.

OBJECTIVE: To examine the relation between indices of maternal nutrition during pregnancy, including haemoglobin concentration, skinfold thickness and body weight, and the child's blood pressure at 10 to 12 years of age. DESIGN: Follow up study of children whose mothers had haemoglobin estimations, weights and skinfold thicknesses recorded during pregnancy. SETTING: Kingston, Jamaica. SUBJECTS: Seventy-seven children whose mothers took part in a prospective study of nutrition during pregnancy in relation to fetal growth. MAIN OUTCOME MEASURE: Blood pressure at 10 to 12 years of age. RESULTS: The child's mean systolic pressure adjusted for current weight rose by 2.6 mmHg (95% CI 0.5-4.6, P = 0.01) for each 1 g/dl fall in the mother's lowest haemoglobin during pregnancy. Mothers with a lower haemoglobin had thinner skinfold thicknesses, especially over the triceps (P = 0.005). In multiple regression analyses, taking account of the child's sex and current weight, there was a strong association between thin maternal triceps skinfold thickness at 15 weeks of gestation and raised blood pressure in the offspring. Taking account of the mother's triceps skinfold thickness abolished the relation between lower haemoglobin and raised blood pressure in the child. Lower weight gain between 15 and 35 weeks of gestation was independently associated with raised children's blood pressure. Systolic pressure rose by 10.7 mmHg (95% CI 5.7 to 15.6, P = 0.0001) for each log mm decrease in the mother's triceps skinfold thickness, and by 0.6 mmHg (95% CI 0.1 to 1.0, P = 0.02) for each 1 kg decrease in the mother's weight gain during pregnancy. CONCLUSIONS: These results parallel animal experiments suggesting that impaired maternal nutrition may underlie the programming of adult hypertension during fetal life.

Blood Pressure

Community based, effective, low cost approach to the treatment of severe malnutrition in rural Jamaica.

Moderate and severe malnutrition are endemic in much of the developing world and in association with pockets of deprivation in the developed world. The cost in terms of individual and social development is high. The principles of effective management are clearly documented. A low cost, community based treatment programme for moderately and severely malnourished children under 3 years of age was established at a health centre in rural Jamaica. Children were followed up monthly and defaulters were rigorously recalled. Management consisted of carefully delivered dietary advice, antibiotics, anthelminthics, and vitamin supplements. All children improved and the response of 36 children, who were treated in the first year, showed an accelerated weight gain, with catch-up growth and the maintenance of length gain. There was a significant increase in the weight for age, at 1.9% per month over six months, which exceeds the rate reported with food supplementation programmes and nutrition rehabilitation centres.

Ambulatory Care Facilities

Interactions between people's diet and their smoking habits: the dietary and nutritional survey of British adults.

OBJECTIVE: To compare diet, nutrient intakes, and biochemical measures between smokers and non-smokers. DESIGN: Analysis of data collected in cross sectional survey conducted in 1986 and 1987. Subjects were recruited from electoral wards in England, Wales, and Scotland to reflect the regional distribution of the population. SUBJECTS: 2197 subjects (70% of those asked) aged between 16 and 64 undertook dietary assessment. Of these, 1842 subjects were considered to have kept a record typical of their usual dietary intake and had given data on smoking, and their results were analysed: 1224 non-smokers (631 men), 359 light smokers (166 men), and 259 heavy smokers (153 men). MAIN OUTCOME MEASURES: Differences in dietary, nutrient, and biochemical measures between nonsmokers and smokers. RESULTS: Smokers ate more white bread, sugar, cooked meat dishes, butter, and whole milk and less wholemeal bread, high fibre breakfast cereals, fruit, and carrots. Smokers had lower intakes of polyunsaturated fat, protein, carbohydrate, fibre, iron, carotene, and ascorbic acid. Adjusting for other covariates did not substantially alter the pattern of intakes. At the same dietary intake of carotenoids smokers were more likely to have lower circulating serum beta carotene concentrations than non-smokers. CONCLUSIONS: The diet and nutrient intakes and circulating levels of nutrients of smokers were different from those of non-smokers. Smokers were more likely to have an imbalance between the dietary intake of antioxidant nutrients and the metabolic demand for antioxidant protection. This imbalance is likely to make smokers more susceptible to oxidative damage. Smokers are at increased risk of chronic disease because their diets are different and because smoking creates an altered pattern of demand for specific nutrients. The diets of smokers not only fail to meet the unusual requirements for specific nutrients to satisfy the altered pattern of demand but are likely to exacerbate the damage caused by smoking.

Adult