Browsing by Subject "fetus"
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Item Arginine and fetal growth in ovine models of intrauterine growth restriction(2009-05-15) Lassala, Arantzatzu LeticiaThis research was conducted to test the hypothesis that parenteralarginine supplementation is effective in enhancing birth weights of intrauterinegrowth restricted (IUGR) fetuses. Underfed and prolific ewes were used asexperimental models. The first study characterized the pharmacokinetics ofarginine and citrulline and assessed the potential of citrulline to serve as aprecursor for enhancing arginine availability in fetal and maternal plasma. Sixlate pregnant ewes and their fetuses were instrumented to access arterial andvenous circulations. Intravenous boluses of 155 mol of L-arginine-HCl or Lcitrullineper kg body weight were administered to each ewe. Administration ofcitrulline was more effective than arginine in achieving a sustained increase inconcentrations of arginine in maternal and fetal blood. Accordingly, theclearance rate of citrulline was lower and its biological half-life in maternal bloodgreater, when compared with arginine. The second experiment determined ifadministration of arginine to underfed ewes is effective in ameliorating orpreventing IUGR. Ewes were fed either 100% or 50% of the National ResearchCouncil recommended nutrient requirements for pregnant sheep. Between Day60 of pregnancy and parturition control-fed ewes received saline solution and underfed ewes received either saline solution or L-arginine-HCl solution (155mol of arginine/kg body weight) intravenously three times daily (n=5 / treatmentgroup). Birth weights of lambs were lower in saline-infused underfed ewes.There was no difference in birth weights of lambs from control-fed and argininetreatedunderfed ewes. The third experiment determined whether administrationof arginine could improve survival rates of lambs and enhance fetal growth inewes carrying multiple fetuses. Between Days 100 and 121 of pregnancy, ewesreceived an intravenous infusion of either saline solution (n= 14) or L-arginine-HCl solution (345 mol of arginine/kg body weight, n=20) three times daily.Parenteral administration of arginine increased the percentage of lambs bornalive and enhanced the birth weights of quadruplets. Collectively, these resultsindicate that 1) parenteral administration of arginine improves pregnancyoutcomes in underfed and prolific ewes; and 2) the use of arginine or citrullinemay have important implications for the design of an effective treatment forpreventing or ameliorating IUGR in mammals.Item A murine model of developmental programming of atherosclerosis(2009-03-30) Nima Goharkhay; George R. Saade, M.D.; Wayne R. Snodgrass M.D, Ph.D.; Monica Longo, MD, Ph.D.; Irina Buhimschi, M.D.; Gary D.V. Hankins, M.D.; Concepcion Diaz-Arrastia, M.D.Early life is increasingly being recognized as an important period of development during which environmental changes can lead to long term effects on an individual’s health. The association between poor nutrition prior to birth and an increased risk to develop coronary heart disease, hypertension and the metabolic syndrome is well established. Animal models are a central tool to investigate the details and mechanistic basis of the effects of the early life milieu. \r\nCoronary artery disease secondary to atherosclerosis remains a major cause of death in most societies. Limited human studies indicate a strong association between maternal hypercholesterolemia and increased rates of formation of atherosclerotic lesions in children. It is conceivable that exposure to a high lipid environment during intrauterine development and early postnatal life may emerge as one of the principal risk factor for premature atherosclerosis.\r\nThese studies were performed to determine the effect of maternal hypercholesterolemia on the risk of atherosclerotic lesion formation in the offspring in a homogenous small animal model. The apoprotein E (apoE)-deficient mouse strain was chosen because of its well described propensity to spontaneously manifest hypercholesterolemia and atherosclerosis. A strong correlation between maternal hypercholesterolemia and an increase in serum cholesterol levels was revealed in chow fed heterozygous litters born to hyperlipidemic dams at both 4 and 8 months of age. In addition, 8-month old heterozygote animals born to apoE-deficient mothers (apoE+/-mat) showed higher rates of atherosclerosis and evidence of liver and kidney damage as compared with their apoE+/-pat counterparts. In contrast, at day 21 of life apoE-/-KO and apoE+/-mat pups showed lower total cholesterol and triglyceride levels than apoE+/+WT or apoE+/-pat litters. \r\nStudies in liver tissue from offspring at 8 months of age suggest activation of the endogenous cholesterol synthetic pathway in apoE+/-mat offspring. This may be one of the mechanisms responsible for the observed programming effects. In-vivo activity and blood pressure measurements and vascular reactivity experiments in 4-month old animals did not demonstrate significant differences among study groups. No marked variation in serum cholesterol levels among genetically similar dams was detected.\r\n