FETAL ALCOHOL SYNDROME ROLE OF PLACENTAL DYSFUNCTION

临床研究和对实验动物的研究表明，母体 乙醇的消费，特别是大量使用，可能会产生毒害作用。 对胎儿和新生儿的影响。在人体内，乙醇的这些毒性作用是 表现为胎儿酒精综合症(FAS)，而在动物中则表现为 生长和发育异常的症状可能是罕见的。机制(S) 其中，乙醇对胎儿的毒性作用仍不确定。同样， 乙醛(乙醇代谢物)、咖啡因和 尼古丁是未知的。然而，人们很欣赏酗酒者 (包括孕妇)倾向于喝大量咖啡和大量吸烟， 咖啡因和尼古丁本身都可能对人体产生有害影响 胎儿。此应用程序的总体目标是评估个人 乙醇、乙醛、咖啡因和尼古丁的联合作用 胎儿的存活、生长和发育。更确切地说，我们希望 检验假设(源自我们单位的广泛研究和 其他人的)乙醇和/或乙醛，可能还有咖啡因和 尼古丁可能会损害胎盘对重要营养物质的运输。这个，如果 进一步的记录可能至少部分解释了胎儿功能障碍 酒精中毒，也可适用于其他人的营养吸收，特别是 胎儿的组织。为了研究这一假设，我们将评估 大鼠和人胎盘不同类型胎盘后选择的氨基酸 单独接触乙醇、乙醛、咖啡因和尼古丁 组合。在大鼠胎盘研究中，怀孕的大鼠将被给予 急性或慢性酒精加或不加咖啡因或尼古丁 注射后胎盘氨基酸转运的体内研究 标记的营养素或随后在体外去除 胎盘。在大鼠和人类胎盘研究中，组织也 会在体外暴露于乙醇、乙醛、咖啡因和尼古丁 (单独和组合)和氨基酸转运将被确定。 任何观察到的变化的机制(S)将从以下方面进行研究 依赖NA、能源需求、结构变化和/或变化 膜脂组成、流动性和Na+-K+-ATPase活性的变化。 类似的研究也将在胎儿组织中进行。我们希望 因此，建立一种促进乙醇诱导胎儿发育的机制 功能障碍，以评估乙醛、咖啡因和尼古丁的作用(S) 在这一点上，也许是为了定义乙醇对组织的更普遍的影响 膜运输。

Clinical studies and those in experimental animals have shown that maternal ethanol consumption, especially in large amounts, may exert toxic effects on the fetus and neonate. In man these toxic effects of ethanol are manifested in the Fetal Alcohol Syndrome (FAS), while in animals a spectrum of growth and developmental abnormalities may be seens. The mechanism(s) of these fetotoxic effects of ethanol is still uncertain. Likewise, the possible roles of acetaldehyde (ethanol metabolite) and of caffeine and nicotine are unknown. It is well appreciated, however, that alcoholics (including pregnant ones) tend to consume much coffee and smoke heavily and that both caffeine and nicotine per se may have deleterious effects on the fetus. The general aims of this application are to assess the individual and combined effects of ethanol, acetaldehyde, caffeine and nicotine on the viability, growth and development of the fetus. More specifically we wish to test the hypothesis (derived from extensive studies in our unit and those of others) that ethanol and/or acetaldehyde and perhaps caffeing and nicotine may impair placental transport of vital nutrients. This, if documented further may explain at least partly, fetal dysfunction with alcoholism and may apply also to nutrient uptake by other, especially fetal, tissues. To investigate this hypothesis we will assess the uptake of selected amino acids by rat and human placenta after various types of exposure to ethanol, acetaldehyde, cafeine and nicotine alone and in combination. In the rat placenta studies, pregnant rats will be given ethanol acutely or chronically with or without caffeine or nicotine and placental amino acid transport will be studied in vivo after injection of the labelled nutrient or subsequent in vitro after removal of the placenta. In both the rat and human placental studies, the tissue also will be exposed in vitro to ethanol, acetaldehyde, caffine and nicotine (singly and in combination) and amino acid transport will be determined. The mechanism(s) of any observed changes will be studied in terms of Na-dependence, energy requirements, structural changes and/or alterations of membrane lipid composition, fluidity and Na+-K+ ATPase activity. Similar studies will be carried out with fetal tissues. We hope to establish thus one mechanisms contributing to enthanol-induced fetal dysfunction, to assess the role(s) of acetaldehyde, caffeine and nicotine in this, and perhaps to define a more general effect of enthanol on tissue membrane transport.