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Biomedical subjects

P Wainwright

Publications and source records attributed to P Wainwright.

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The quantitative relationship between nutritional effects on preweaning growth and behavioral development in mice.

Our objective was to establish whether nutritional effects on the behavioral development of preweaning mouse pups were linearly related to effects on body and brain growth or whether there was a threshold effect, with behavior being affected only by nutritional extremes. We also used a standardized scale of development to compare the relative magnitude of such effects on morphological and behavioral measures. The level of nutrient availability was manipulated continuously by rearing the pups in litter sizes ranging from 3 to 12. On Day 32 post-conception, measures were taken of body weight, brain weight, thickness of the cerebellar external granular layer (EGL), and behavioral development. The relationship between litter size and body weight, brain weight, and behavioral development was best described by a linear regression model; no threshold effect was apparent. By comparing measures on animals from different litter sizes at the same age (32 days) to standard developmental curves over a wide range of ages, we found that for every additional pup in a litter, body growth was retarded by the equivalent of 1.28 days, brain weight by 0.44 day, and behavioral development by 0.07 day. Although the variation in nutrient availability provided by this range of litter sizes does result in a linear relationship between growth and behavioral development, there is nevertheless considerable sparing of function.

Animals

Effects of preweaning nutrition on weight gain during pregnancy in mice.

Previous work has shown that preweaning litter size affects the response of adult mice to dietary induced obesity, with animals reared in small litters showing increased hyperphagia and weight gain. The present work addressed whether a similar effect would be seen in the weight changes normally accompanying pregnancy and lactation. B6D2F2 mice were reared in small (4), medium (8) and large (12) litters. Adult females from each of these conditions were mated with males from medium litters and their body weight and food intake measured throughout pregnancy and lactation. Food intake increased during pregnancy and correlated with the dams' litter size, but the amounts consumed by all groups appeared similar. This was also true of maternal weight gain during pregnancy, pup weight and litter size. During lactation, the only differences were that animals which had been reared in large litters ate more food and weaned heavier pups than those in medium litters. These results differ from those previously obtained on dietary induced obesity, supporting different regulatory mechanisms in the two conditions.

Adipose Tissue

Heredity and alcohol-induced brain anomalies: effects of alcohol on anomalous prenatal development of the corpus callosum and anterior commissure in BALB/c and C57BL/6 mice.

Using two inbred strains of mice which have similar rates of alcohol metabolism, we asked whether prenatal alcohol exposure would cause greater incidence and severity of defects in the development of two forebrain fiber tracts, the corpus callosum and the anterior commissure, in mice prone to these defects (BALB/c) than in mice not prone to these defects (C57BL/6). Pregnant animals were fed 0.6 kcal/g body weight of a Sustacal-based liquid diet containing 0, 15, 17.5, 20, or 25% ethanol-derived calories from day 7 to fetal assessment on day 18 of gestation. Most of alcohol's greatest effects and the greatest strain differences in alcohol's effects on fetal variables were produced by the 17.5% diet. This dose had inhibitory effects on fetal body, brain, and midsagittal corpus callosum and anterior commissure growth. All these effects, except that on brain weight, were significantly greater in C57s than in BALBs. When the results were compared with prenatal growth curves for normal untreated mice, the effect of alcohol on corpus callosum but not anterior commissure growth was largely explained by its effects on overall development. The 17.5% diet had a greater specific effect on size of the anterior commissure in C57s than BALBs but increased the incidence and severity of its permanent dysmorphology in BALBs more than in C57s. Anterior commissure size and morphology may be sensitive indicators of alcohol's effects on prenatal brain development. Hereditary differences in rate of maternal alcohol metabolism no doubt have important consequences for risks arising from prenatal alcohol exposure. However, this study clearly indicates that inherited factors, other than those that influence rate of alcohol metabolism, are important influences on the overall fetal response and the specific responses of the anterior commissure to prenatal alcohol exposure.

Abnormalities, Drug-Induced

Differential early rearing affects response to overfeeding in B6D2F2 mice.

Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters, were maintained on high-fat, high-carbohydrate (EXP) or chow (CH) diets beginning at 14 weeks. EXP mice consumed more calories and gained more weight than CH mice; these effects were greatest in the Sm animals. Each sex responded similarly. Caloric efficiency was highest in the Sm EXP and male animals. Total body fat in males showed that Sm greater than Md greater than Lg and EXP greater than CH. The thermogenic capacity was measured by total oxygen consumption and body temperature response during acute cold stress, and protein content and cytochrome c oxidase activity in interscapular brown adipose tissue (1BAT). Sm mice had a smaller decrease in temperature and consumed less oxygen per gram body weight than Lg, suggestive of a contributing role of increased insulation. When oxygen consumption was expressed as a function of body weight0.75, EXP greater than CH, but there were no other significant dietary effects. Neither litter size nor diet appeared to affect protein content or cytochrome c oxidase activity in 1BAT. These results show that early rearing experience effects both behavioural and physiological variables associated with the maintenance of adult body weight in mice, but these effects do not appear to be mediated through 1BAT.

Animals

Effect of pre- and postweaning nutrition on dietary induced obesity in B6D2F2 mice.

Our purpose was to ascertain whether a phase of postnatal overfeeding would interact with preweaning litter size in influencing dietary induced obesity in mice. Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters were maintained on high fat (HF) or control diets (C) for 6 weeks, beginning at weaning. After a further 4 weeks on lab chow, all animals were fed a cafeteria diet for another 6 week period. Body weight at weaning indicated Lg less than Md and Sm animals. Lg animals gained more weight during the postweaning period but their body weight remained lower than the Sm. HF animals from all litter sizes consumed more calories and gained more weight than C animals. During the period of cafeteria feeding the Sm animals gained more weight than the Md and Lg. Although males were heavier than females, the sexes responded similarly to treatment. The postweaning dietary regimen had no effect on the weight gained in response to cafeteria feeding.

Animals

The interaction of cytochrome C with phospholipids. A pulse-radiolysis study.

The reactions of the hydrated electron (eaq-), produced during pulse radiolysis, have been used to study the binding of phosphatidyl choline (PC), phosphatidyl serine (PS), phosphatidyl ethanolamine (PE), and phosphatidyl inositol (PI) vesicles with horse-heart cytochrome C. An interaction could only be detected between cytochrome C and either PS or PI. An apparent equivalence point in the binding was reached for both phospholipids at a molar ratio of phospholipid : protein of 6 : 1. At this point, the reactivity of (eaq-) towards the cytochrome C was very markedly reduced. Indeed, the rate of disappearance of (eaq-) under such conditions was the same as the rate of eaq- disappearance in triply-distilled water. The inclusion of cholesterol at a molar ratio of 1 : 1 within the phospholipid vesicles changed the stoichiometry of the interaction. Evidence that protonated epsilon-amino groups of lysine residues are involved in the interaction is presented. Possible models for the complexes formed are discussed.

Cholesterol

gamma-Linolenic acid fails to prevent the effects of prenatal ethanol exposure on brain and behavioral development in B6D2F2 mice.

The purpose of this study was to obtain a quantitative assessment of the behavioral retardation caused by prenatal ethanol exposure in mice and to test the hypothesis that gamma-linolenic acid (GLA) supplementation would prevent such effects. Pregnant B6D2F1 mice were fed liquid diets containing 25% ethanol-derived calories from days 7-17 of gestation. The experimental groups were given GLA via subcutaneous injection; the control was administered vehicle only. All groups were pair fed to this ethanol control, including a second control group which received sucrose substituted isocalorically for ethanol. Additional control groups included one fed lab chow ad libitum and two further ethanol groups, one treated with coconut oil, the other with arachidonic acid (AA). Behavioral development of the pups was measured on day 32 postconception and open field behavior was measured on day 50. Body and brain weight were also measured. The results indicated that reproductive outcome, as measured by animals which produced live pups, was worse in the GLA- and AA-treated groups. Ethanol produced significant behavioral retardation of the order of 1.7 days. Body and brain weight were lower in ethanol-treated pups. Covariance analysis indicated that the effect on brain weight was independent of the effect on body weight. Open field scores suggested that ethanol-treated males were more active then sucrose controls. The data did not support the hypothesis that GLA would prevent the deleterious effects of prenatal ethanol exposure; in no instance was a GLA-treated group different from the ethanol control.

Animals

Do nurses have ethics?

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Ethics, Nursing