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Biomedical subjects

S C Langley-Evans

Publications and source records attributed to S C Langley-Evans.

At least 19 recordsLinked to original sources
PubMed2006

Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats.

OBJECTIVE: To assess the long-term impact of undernutrition during specific periods of fetal life, upon central adiposity, control of feeding behaviour and locomotor activity. DESIGN: Pregnant rats were fed a control or low-protein (LP) diet, targeted to early (LPE), mid (LPM) or late (LPL) pregnancy or throughout gestation (LPA). The offspring were studied at 9 and 18 months of age. MEASUREMENTS: Adiposity was assessed by measuring weight of abdominal fat depots relative to body weight. Locomotor activity was assessed using an infrared sensor array system in both light and dark conditions. Hypothalamic expression of mRNA for galanin and the galanin 2 receptor (Gal2R) was determined using real-time PCR. RESULTS: At 9 months, male rats exposed to LP in utero had less fat in the gonadal depot, but were of similar body weight to controls. By 18 months, the males of groups LPA and LPM had more abdominal and less subcutaneous fat. Females deposited more fat centrally than males between 9 and 18 months of age, and this was more marked in groups LPA and LPL. Food intake was greater in LPM males. Among females hypophagia was noted in groups LPA and LPL. Expression of galanin and Gal2R were unaffected by maternal diet. Total locomotor activity was reduced in LPE males and all LP females in the light but not in the dark. CONCLUSION: Locomotor activity and feeding behaviour in aged rats are subject to prenatal programming influences. Fetal undernutrition does not programme obesity in rats without postnatal dietary challenge.

Aging↗
PubMed2006

Diet and the developing immune system.

Undernutrition during fetal life is known to have programming effects upon tissue morphology and function. This generally promotes poor health in adult life, with increased risk of metabolic syndrome and cardiovascular mortality noted among individuals whose growth was constrained in utero. Undernutrition in early life impacts upon the development of the immune organs and appears to diminish cellular immunity and increase the risk of atopic disorders during childhood. A limited body of evidence implicates fetal programming in the development of autoimmune disorders. This area represents an interesting target for further research and preventive medicine.

Animals↗
PubMed2005

Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep.

The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28-80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100-150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (se 2); LBCS, 77 (se 3); NR, 77 (se 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (se 6); NR, 56 (se 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

Nutritional programming of blood pressure and renal morphology.

A range of epidemiological evidence from several diverse populations, supports the hypothesis that risk of essential hypertension, coronary heart disease and non-insulin dependent diabetes is, in part, programmed by intrauterine nutritional status. Animal models developed to investigate the mechanisms that are responsible for such programming are becoming more important as challenges to the epidemiological data become more robust. With strong evidence from animal studies it is now widely accepted that maternal nutritional status in pregnancy is a major programming influence upon the fetus. This paper considers the hypothesis that renal structure and function are determined by prenatal nutrition and that this is a key mechanism in the programming of hypertension. The feeding of low protein diets or other insults in pregnancy that have an impact upon the development of cardiovascular functions, also appears to impact upon nephron number. In the sheep nephron number is related to weight at birth following nutrient restriction, and in the rat low protein diets reduce nephron number by approximately 30%. However, it is possible that hypertension and reduced renal reserve merely coincide and are not causally associated. A study of rats fed low protein diets supplemented with additional nitrogen sources found that whilst only glycine could reverse the hypertensive effects of low protein diets, all supplements could normalise nephron number. The evidence thus suggests that prenatal undernutrition may programme renal structure in later life, but that renal programming is not one of the primary mechanisms leading to hypertension.

Animals↗
PubMed2003

Relationship between maternal nutrient intakes in early and late pregnancy and infants weight and proportions at birth: prospective cohort study.

Experimental studies indicate that fetal undernutrition programmes life-long physiology and disease risk. The objective of this study was to investigate relationships between maternal nutrient intakes in early and late pregnancy with birth weights, placental weights, and infant proportions at birth. A prospective cohort study set in a district general hospital in the east midlands of England considered the diets of 300 pregnant women recruited from an antenatal ultrasound dating scan clinic. Estimation of nutrient intakes utilised five-day food diaries in the first and third trimesters of pregnancy. Two hundred and four diaries were returned and analysed for trimester one and 176 for trimester three. Birth weight and infant head circumference at birth were unrelated to nutrient intakes in the first or third trimester of pregnancy. Placenatal weight was not related to any maternal nutrient intakes. Thinness at birth was associated with low contributions of carbohydrate to dietary energy (p = 0.036). The present study shows that maternal nutrition in well-nourished populations does not exert a strong influence upon fetal growth. These data suggest that reported associations between low weight, thinness or greater head circumference at birth and disease in later life are not attributable to the effects of maternal undernutrition.

Adult↗
PubMed2001

Fetal programming of cardiovascular function through exposure to maternal undernutrition.

A substantial and robust body of epidemiological evidence indicates that prenatal dietary experience may be a factor determining cardiovascular disease risk. Retrospective cohort studies indicate that low birth weight and disproportion at birth are powerful predictors of later disease risk. This prenatal influence on non-communicable disease in later life has been termed programming. Maternal nutritional status has been proposed to be the major programming influence on the developing fetus. The evidence from epidemiological studies of nutrition, fetal development and birth outcome is, however, often weak and inconclusive. The validity of the nutritional programming concept is highly dependent on experimental studies in animals. The feeding of low-protein diets in rat pregnancy results in perturbations in fetal growth and dimensions at birth. The offspring of rats fed low-protein diets exhibit a number of metabolic and physiological disturbances, and are consistently found to have high blood pressure from early postnatal life. This experimental model has been used to explore potential mechanisms of programming through which maternal diet may programme the cardiovascular function of the fetus. Indications from this work are that fetal exposure to maternally-derived glucocorticoids plays a key role in the programming mechanism. Secondary to this activity, the fetal hypothalamic-pituitary-adrenal axis may stimulate renin-angiotensin system activity, resulting in increased vascular resistance and hypertension.

Animals↗
PubMed2001

Nausea and vomiting of pregnancy: endocrine basis and contribution to pregnancy outcome.

For a majority of women, nausea and vomiting of pregnancy (NVP) is an unpleasant but normal feature of pregnancy. NVP has a largely unknown etiology, but it is widely agreed that physiological, psychological, genetic, and cultural components are contributing factors. The occurrence of NVP may be of benefit in pregnancy, and NVP-associated pregnancies are less likely to result in miscarriage, preterm delivery, or intrauterine growth retardation. It has been suggested that NVP is promoted by secretion of human chorionic gonadotrophin (hCG), largely on the basis of the coincidence between the onset of NVP and hCG secretion and the peaks of both at around 12 to 14 weeks' gestation. Concentrations of hCG that are above or below the normal range are associated with poor pregnancy outcomes. It seems that NVP and hCG are related and that nutrient restriction during critical periods of embryonic development may ensure production of hCG at optimal levels, protect placental development, and optimize nutrient partitioning between maternal and fetal tissues.

Abortion, Spontaneous↗
PubMed2000

Critical differences between two low protein diet protocols in the programming of hypertension in the rat.

Maternal nutrition has been identified as a factor determining fetal growth and risk of adult disease. In rats, the feeding of a low protein diet during pregnancy retards fetal growth and induces hypertension in the resulting offspring. Rat models of low protein feeding have been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease and diabetes. Low protein diets of differing composition used in different laboratories have yielded inconsistent data on the relationship between maternal protein intake and offsprings' blood pressure. Two separate low protein diet protocols were compared in terms of their ability to programme hypertension during fetal life. Pregnant rats were assigned to receive one of four diets. Two diets were obtained from a commercial supplier and provided casein at 22 or 9% by weight (H22, control; H9, low protein). The other two diets, manufactured in our own facility, provided 18% casein (S18, control) or 9% casein (S9, low protein) by weight. The diets differed principally in their overall fat content, fatty acid composition, methionine content and the source of carbohydrate. Feeding of the experimental diets commenced on the first day of pregnancy and continued until the rats delivered their litters. Following weaning all the offspring had blood pressure determined on a single occasion. Both low protein diets reduced maternal weight gain relative to their corresponding control diets. Despite this litter sizes were unaffected by the dietary protocols. Both low protein diets reduced birthweights of the pups. Systolic blood pressure was significantly elevated in the offspring of rats fed a low protein S9 diet relative to all other groups (P < 0.05). Animals exposed to H9 diet in utero had similar blood pressures to their H22 controls. It is concluded from this work that differing low protein diet manipulations in rat pregnancy elicit different programming effects upon the developing cardiovasculature. The balance of protein and other nutrients may be a critical determinant of the long-term health effects of maternal undernutrition in pregnancy.

Animals↗
PubMed2000

Consumption of black tea elicits an increase in plasma antioxidant potential in humans.

Epidemiological studies suggest that the consumption of tea flavonoids may be associated with reduced risk of coronary heart disease, stroke and cancer-related deaths. The flavonoids are polyphenols which in vitro exhibit antioxidant properties. Tea flavonoids are known to be rapidly absorbed into the circulation following oral ingestion. To date few studies have demonstrated that these bioavailable flavonoids retain antioxidant properties in vivo. Nine healthy subjects aged between 26 and 59 (one male and eight females) took part in 3 study days. On 1 day subjects consumed no tea and on the other 2 days subjects drank either black tea with milk, or black tea alone at hourly intervals between 9.00 a.m. and 14.00 p.m. Blood was sampled at 9.00 a.m. and at 12.00 p.m. and 15.00 p.m. The antioxidant potential of plasma was determined using the ferric reducing antioxidant power (FRAP) assay. Subjects consuming no tea exhibited no significant change in FRAP across the 6 hours of the study day. Similarly consumption of milky tea produced no change in FRAP between 9.00 a.m. and 12.00 p.m. and the 50% increase in FRAP noted between 12.00 p.m. and 15.00 p.m. was not statistically significant. When the subjects consumed black tea without milk FRAP increased by 65% between 9.00 a.m. and 12.00 p.m. (P = 0.02) and at 15.00 p.m. was 76% higher than at 9.00 a.m. (P = 0.002). Heavy consumption of black tea thus appears to elevate circulating antioxidant potentials in vivo. This is an effect which appears to be totally negated by the drinking of tea with milk. Although tea may thus represent an important source of dietary antioxidants in many societies, the role of tea in reducing risk of major disease states needs to be investigated in more detail.

Adult↗
PubMed2000

Antioxidant potential of green and black tea determined using the ferric reducing power (FRAP) assay.

Tea is one of the most commonly consumed beverages in the world and is rich in polyphenolic compounds collectively known as the tea flavonoids. Tea flavonoids possess antioxidant properties in vitro and have been proposed as key protective dietary components, reducing risk of coronary heart disease and some cancers. The present study aimed to evaluate the possible effects of different preparation methods on the antioxidant properties of green and black tea. Antioxidant potentials of tea infusates were assessed using an assay based upon the reduction of ferric chloride linked to a chromophore. Green tea, black leaf tea and black tea in tea bags were infused with water at 90 degrees C for time periods ranging from 0.25 to 15 min. Green tea infusates possessed approximately 2.5-fold greater antioxidant capacity than both types of black tea infusates. Both green and black teas released significant levels of antioxidants into the hot water within 2 min of infusion. Preparation of teas across a range of temperatures between 20 and 90 degrees C revealed that although antioxidants were liberated from the leaves into the water in cooler infusions, increasing the temperature could increase antioxidant potential by 4 to 9.5-fold. Black tea prepared using tea bags had significantly lower antioxidant capacity than black leaf tea at temperatures between 20 and 70 degrees C, suggesting that tea bag materials may prevent some extraction of flavonoids into the tea solution. The addition of milk appeared to diminish the antioxidant potential of black tea preparations. This effect was greatest where whole cow's milk was used and appeared to be primarily related to the fat content of the added milk. These experiments have considered the effects of commonly used domestic methods of preparation on the in vitro antioxidant potential of tea. It is concluded that maximum antioxidant capacity and hence maximal health benefit may be derived from green tea or from black leaf tea prepared by infusion with water at 90 degrees C for up to 2 min and taken with the addition of either fat-free milk, or without milk addition. Further studies are required to assess the antioxidant actions of tea flavonoids in vivo.

Animals↗
PubMed2000

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat.

Epidemiological evidence from diverse human populations, supported by experimental evidence from animal models, suggests that maternal nutrition during pregnancy is an important fetal programming influence upon cardiovascular disease. Experiments with a low-protein-diet model of rat pregnancy suggest a role for the renin-angiotensin system in the programming mechanism, since fetal undernutrition permanently elevates pulmonary and plasma angiotensin-converting enzyme activity. Long-term beneficial effects of captopril on blood pressure in this model require further investigation in order to clarify the role of angiotensin II. Pregnant rats were fed a control diet containing 18% (w/w) casein as the protein source or a low-protein diet containing 9% (w/w) casein. Between the ages of 2 and 4 weeks postnatally, mothers and their pups were treated with losartan or nifedipine. All pups in the study had blood pressure determined at 4 and 12 weeks of age using a tail cuff. Animals exposed to the low-protein diet in utero and not subjected to drug treatment had elevated blood pressure relative to control rats (mean increase of 27 mmHg; P<0.001). Treatment of rats exposed to the control diet in utero with either nifedipine or losartan between 2 and 4 weeks of age did not alter their blood pressure. Nifedipine had no effect upon the blood pressure of low-protein-exposed pups, but losartan prevented the blood pressure elevation in these animals. Between 4 and 12 weeks of age, blood pressure increased significantly in all groups (P<0.001). The pattern of blood pressure among the groups was identical to that observed at 4 weeks, suggesting that the observed early effects of losartan would be maintained into adult life. The data are consistent with the hypothesis that angiotensin II plays a major role in the prenatal programming of hypertension. The action of angiotensin II at the AT(1) receptor between 2 and 4 weeks of age may be critically up-regulated by fetal factors, including exposure to glucocorticoids of maternal origin.

Analysis of Variance↗
PubMed2000

Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero.

Intrauterine growth retardation associated with maternal undernutrition is proposed to play a significant role in the aetiology of hypertension and CHD. Animal experiments suggest that the kidney, which is extremely vulnerable to the adverse effects of growth-retarding factors, may play an important role in the prenatal programming of hypertension. Maintenance of renal haemodynamic functions following structural impairment in fetal life is proposed to require adaptations which raise systemic blood pressure and promote a more rapid progression to renal failure. Rats were fed on diets containing 180 g casein/kg (control) or 90 g casein/kg (low protein) during pregnancy. The offspring were studied in terms of blood pressure, creatinine clearance, blood urea N, plasma and urinary albumin, renal morphometry and metabolic activity at 4, 12 and 20 weeks of age. Blood pressure was elevated at all ages in the low-protein-exposed offspring, relative to control rats. Rats (4 weeks old) exposed to the low-protein diet had smaller kidneys which were shorter and wider than those of control animals. Creatinine clearance was significantly reduced in 4-week-old rats exposed to the low-protein diet. Renal morphometry and creatinine clearance at older ages were not influenced by prenatal diet. Blood urea N, urinary output and urinary albumin excretion were, however, significantly greater in low-protein-exposed rats than in control rats at 20 weeks of age. These findings are suggestive of a progressive deterioration of renal function in hypertensive rats exposed to mild maternal protein restriction during fetal life. This is consistent with the hypothesis that adaptations to maintain renal haemodynamic functions following impairment of fetal nephrogenesis result in an accelerated progression towards glomerulosclerosis and increased intrarenal pressures mediated by rising vascular resistance.

Albumins↗
PubMed1999

Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat.

Epidemiological evidence suggests that hypertension and coronary heart disease are programmed by exposure to a poor diet during intrauterine life. It has been proposed that the prenatal environment may exert an adverse effect on the development of the kidney and hence later control of blood pressure. These assertions are supported by animal experiments. In the rat, fetal exposure to a maternal low protein diet is associated with disproportionate patterns of fetal growth and later elevation of blood pressure. Pregnant female rats were fed control (18% casein) or low protein diets throughout pregnancy, or during specific periods. Nephron number was determined at day 20 gestation, full term and 4 weeks of age. Exposure to low protein throughout gestation, or in mid-late gestation increased total nephron number at day 20. By term nephron number was reduced, relative to controls, in rats that were undernourished between days 8-14 or 15-22 gestation. At 4 weeks postnatally rats exposed to low protein throughout fetal life had a reduced (13%) nephron complement and blood pressures 13 mmHg above control animals. Lower renal size and elevated blood pressure persisted to 19 weeks of age, at which time glomerular filtration rate was normal. The data are consistent with the hypothesis that maternal undernutrition may programme the renal nephron number and hence impact upon adult blood pressure and the development of renal disease.

Animals↗
PubMed1999

Intrauterine programming of hypertension: the role of the renin-angiotensin system.

From experiments with prenatal undernutrition in the rat, it is clear that fetal exposure to glucocorticoids of maternal origin is a key first step in the programming of hypertension and perhaps coronary heart disease. The chain of events leading from glucocorticoid action in the fetal tissues to hypertension in adulthood involves the development of hypersensitivity to glucocorticoids in adult life (Scheme 1). This has the effect of activating the RAS through induction of key genes such as ACE, which, in turn, may increase sensitivity of the blood vessels to the actions of ANGII. Another consequence of prenatal undernutrition, which may or may not involve glucocorticoids, is the abnormal development of the kidney [35]. Impaired nephrogenesis must surely have an impact upon lifelong renal function and cardiovascular control. Progress has been made in demonstrating that hypertension can be prenatally programmed through maternal dietary manipulation and some of the putative mechanisms involved have been identified. The priorities in this field of research must now be to clarify the role of maternal diet as a programming stimulus in order to generate an effective series of public health guidelines for pregnant women. Although the identification of metabolic mechanisms might suggest possible pharmacological interventions in early life as a means of reducing cardiovascular risk in adult life [49], it will always be more desirable to optimize maternal diet.

Adult↗
PubMed1999

Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat.

Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension.

Animals↗
PubMed1998

Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets.

Epidemiological evidence that hypertension and coronary heart disease are programmed by exposure to poor diet during intrauterine life, is supported by animal experiments. In the rat, fetal exposure to a maternal low protein diet is associated with abnormal fetal growth and later elevation of blood pressure. Fetal exposure to glucocorticoids of maternal origin are proposed to underlie this association. Pregnant female rats were fed control (18% casein) or moderately low protein diets (9% casein). Feeding of low protein was either throughout gestation (d0-22), or for specific periods (d0-7, d8-14, d15-22). Fetal and placental weight were determined at d14, 20 and 22. Low protein feeding in the periods d0-7, d8-14, d0-14 stimulated fetal growth to d14. At d20 gestation low protein exposed fetuses tended to be smaller than control fetuses, although low protein d8-14 fetuses were significantly larger than controls. Animals exposed to low protein diets were of lower weight at birth and had higher blood pressure at 4 weeks postnatal age. The activities of glucocorticoid-inducible enzymes in brain (fetal and neonatal) and liver (neonatal) were specifically elevated relative to control animals, by low protein exposure. The data suggest that low protein exposure, particularly in late gestation is associated with increased fetal glucocorticoid-exposure. This may both retard fetal growth and programme later increases in systolic blood pressure.

Animals↗
PubMed1998

Intrauterine programming of cardiovascular disease by maternal nutritional status.

The origins of cardiovascular disease are related to genetic factors, postnatal environmental and behavioral influences, and also the environment experienced in utero. Patterns of disproportionate fetal growth consistent with maternal undernutrition appear to be predictive of later hypertension and coronary heart disease. These findings from epidemiologic studies are strongly supported by animal studies. Experimental models are suggestive of a role for glucocorticoid hormones in the intrauterine programming of cardiovascular function. New understanding of the relationships between maternal diet and the development and maturation of fetal tissues may enable prevention of cardiovascular disease by intervention in early life.

Cardiovascular Diseases↗