Effects of different liquid diets and sustained ethanol release on alcohol metabolism

The effects of two liquid diets, Sustacal and Shorey-AIN, on liver alcohol dehydrogenase (ADH) activity and ethanol clearance were tested in rats under conditions of high ethanol exposure for nine days. High blood ethanol levels (BEL) were produced through a combination of an initial intubated dose of ethanol, sustained ethanol release tube (SERT), and ethanol as 37% of total energy in the liquid diet. Under free-feeding conditions, rats consumed slightly more ethanol per unit body weight in the Shorey-AIN diet, a diet formulated for rodent nutrition, than in the Sustacal diet, a diet originally intended for human consumption. However, BEL were significantly higher in the Sustacal group than in the Shorey-AIN group. No differences in ethanol clearance rates were observed between the groups. On the other hand, total liver ADH activity was significantly reduced in both the Shorey AIN/ethanol and the Sustacal/ethanol groups, compared to lab chow controls. When the Sustacal diet was fortified with casein and methionine so that the protein content matched that of the Shorey AIN diet, the BEL were no longer significantly higher than those produced by the Shorey AIN/ethanol diet. The results demonstrate the effect of nutritional factors on BEL under conditions of high ethanol load. However, these factors do not appear to alter major characteristics of ethanol metabolism and clearance in our short-term experiments.     

Breast pumping and lactational state exert differential effects on ethanol pharmacokinetics

Prior research revealed that breast stimulation altered the way the lactating body handles alcohol. Its effects depended upon when it occurred relative to drinking. The goal of the present study was to determine whether breast pumping works independently of the physiological and metabolic changes that accompany lactation. To this end, we tested 12 women when they were exclusively breastfeeding 3-5-month-old infants and then again several months after lactation had ceased. Subjects were randomly assigned to one of two groups that differed in the timing of breast pumping relative to drinking a 0.4 g/kg dose of alcohol: one group breast pumped 0.6 h after drinking (pumped after group) and the other pumped 1 h before drinking (pumped before group). For each reproductive stage, subjects were tested on 2 separate days, consuming a standardized meal 1 h before drinking during 1 test day and remaining fasted during the other. Breath alcohol concentrations (BrAC) and temperature readings were obtained before and at fixed intervals after drinking. Pumping before drinking significantly decreased BrAC during both reproductive stages, whereas pumping after drinking resulted in different BrAC time curves during lactation when compared with after lactation. That is, levels were significantly lower during the descending phase of the time curve during than after lactation. The interactions between pumping and reproductive stage were most apparent during fed condition. Furthermore, women were more sensitive to hypothermic effects of both fasting and drinking alcohol during lactation. These findings add to the growing literature that lactating women metabolize alcohol differently, in part, due to the frequent breast stimulation during breastfeeding and the pronounced physiological changes that accompany one of the most energetically costly mammalian activities.     

口服钙片对试验人群血压水平的影响

目的 评价口服乳酸钙片后对血压水平的作用以及对血清中主要元素如钠、钾、钙、磷的影响。方法 对山西某一低钙、高盐膳食及血压均值、患病率较高的农村自然人群,在人群血压筛查的基础上,从３０～６４岁志愿选出１１２名,采用随机双盲对照的方法,分别服用酸钙片（每日补钙８００ｍｇ）安慰剂,观察５周后进行有关复查。其中９８名志愿完成了试验（男３９人,女５９人）。结果 口服３５ｄ钙片后与安慰剂组比较,收缩压净下     

Interindividual variations in the disposition and metabolism of ethanol in healthy men

Forty-eight healthy men each drank a dose of ethanol, 0.68 g/kg of body weight, as neat whisky at about 09.00, after fasting overnight. The drink was finished within 20 min and the concentrations of ethanol in samples of capillary blood were determined at 30–60 min intervals for 7 hr. Rectilinear regression lines were fitted to the elimination phase of blood concentration time profiles and blood-ethanol parameters were calculated as described by Widmark. In 23, 14, 8 and 3 subjects the peak blood ethanol concentrations were reached at 30, 60, 90 and 120 min timed from starting to drink. The highest concentration of ethanol in blood was 0.92±0.022 mg/ml (mean ±SE) and the coefficient of variation (CV) was 16.8%. The blood concentration of ethanol extrapolated to zero-time was 0.98±0.009 mg/ml (CV=6.5%) and the apparent volume of distribution (V_d) was 0.695±0.0064 L/kg (CV=6.4%). The rate of ethanol elimination from blood was 0.126±0.0018 mg/ml/hr (CV=9.9%) and the body clearance was 87.5±1.1 mg/kg/hr (CV=8.7%). The apparent volume of distribution of ethanol was inversely related to the subject's body weight (r=?0.59±0.118, p<0.001). The elimination rate from blood was lower in those subjects with larger distribution volume; the parameters were negatively correlated (r=?0.52±0.126, p<0.001). The results show that blood-ethanol parameters calculated according to Widmark's method have low intersubject variability when the dose of ethanol administered and the condition of the test subjects are carefully controlled. A more sophisticated mathematical treatment of ethanol pharmacokinetics may be unnecessary.     

A comparison of the central nervous system effects of alcohol at pseudo-steady state in Caucasian and expatriate Japanese healthy male volunteers

In general, Japanese and Caucasians differ in their response to alcohol. To investigate these differences the alcohol clamping method can be used. This strictly controlled infusion regimen provides a reliable tool to study contrasts in central nervous system (CNS) effects and/or alcohol disposition. In this study, twelve Japanese and twelve Caucasian healthy volunteers received two concentrations of intravenous alcohol or placebo using the alcohol clamp. Infusion rates during the steady state phase were used to compare alcohol clearance between the subgroups. Central nervous system (CNS) effects were frequently measured throughout the clamp. On average, significantly lower amounts of alcohol were needed to maintain similar stable concentrations in the Japanese group. However, these differences disappeared when values were corrected for lean body mass. The most pronounced pharmacodynamic differences between the groups were observed on body sway and on the visual analogue scale for subjective alcohol effects, mainly at the highest dose level. The alcohol clamp seems a useful method to compare differences in alcohol metabolism between groups. Some CNS effects of alcohol differed clearly between Japanese and Caucasians, but others did not, even though alcohol levels were stable and similar between the two groups.     

The effect of ethanol and calcium on fluid state of plasma membranes of rat hepatocytes

Basolateral (blLPM) and canalicular (cLPM) plasma membrane vesicles were isolated from rat liver to compare membrane fluidity, fluidity responses to membrane perturbants, and the relationship between fluidity and a membrane protein function such as carrier-mediated taurocholate transport. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe. Uptake of [3H] taurocholate was measured by a rapid Millipore filtration technique. blLPM were more fluid than cLPM. Ethanol produced a concentration-dependent fluidizing effect on both membrane preparations, the change being greater in blLPM. Incubation with calcium for 2 hr at 37 degrees C rendered both membrane preparations more rigid, again the cLPM being more resistant to perturbation. There was a linear correlation between an increase in membrane fluidity and inhibition of taurocholate uptake into blLPM in the presence of increasing concentrations of ethanol. The data support the concept that membrane lipid fluidity is an important regulator of membrane protein functions and hence also of overall cellular activity.     

钙通道阻滞剂对大鼠肝移植冷保存再灌注损伤中细胞内钙的影响

目的研究钙通道阻滞剂对减轻肝移植中冷保存再灌注下肝细胞的钙超载及保护肝脏的作用。方法64只W istar大鼠行原位肝移植,按灌洗保存液的不同成分分组:⑴对照组:高渗枸椽酸盐腺嘌呤液(HCA);⑵实验I组:HCA液 维拉帕米;⑶实验II组:HCA 硝苯地平;⑷实验III组:HCA 硫氮卓酮,测定冷保存再灌注后的大鼠肝细胞内钙和肝功能,并在光镜和电镜下观察肝脏的结构。结果细胞内钙及肝功能测定,各实验组与对照组相比较差异有统计学意义(P<0.05);组织学观察,各实验组损伤轻于对照组。结论钙通道阻滞剂对肝移植中冷保存再灌注损伤的肝脏有保护作用,且三类药物中维拉帕米最强,硝苯地平和硫氮卓酮次之。     

Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized,double-blind,placebo-controlled,clinical trial

PurposeTo estimate the effects of calcium or vitamin D supplementation or a combination of both on blood pressure and serum lipid and carotenoid levels.MethodsNinety-two colorectal adenoma patients were randomized in a pilot, double-blind, placebo-controlled clinical trial of supplemental vitamin D₃ 800 IU and elemental calcium 2.0 g (as calcium carbonate) alone or in combination in divided doses twice daily with meals over 6 months.ResultsRelative to placebo, mean serum triglycerides decreased 30% (P = .10) and 32% (P = .10) in the calcium and calcium plus vitamin D₃ treatment groups, respectively. When the two calcium intervention groups were pooled and compared with the pooled noncalcium groups, the estimated supplemental calcium treatment effects were statistically significant for triglycerides (P = .04). Similar but nonstatistically significant decreases (5%–7%) were observed for serum total cholesterol levels. Mean systolic blood pressure increased 6% (P = .08) in the calcium group; otherwise, there were no appreciable changes in systolic or diastolic blood pressures in any active treatment group. Mean serum total carotenoid levels decreased 14% (P = .07) in the calcium and 9% (P = .10) in the calcium plus vitamin D₃ groups.ConclusionsOur results suggest that supplemental calcium alone or combined with vitamin D₃ but not vitamin D₃ alone may reduce serum lipids and lipophilic micronutrients.     

补充钾和钙对血压偏高青年动脉血压及钠代谢影响的长期观察

目的　观察在食盐中添加钾和钙降低血压偏高青年动脉血压的作用及其对钠代谢的影响。方法　选取年龄 18～ 2 2岁的 2 2 0名血压偏高青年 ,采用随机、单盲、对照的方法分为补充钾钙组110名 (男 5 8名 ,女 5 2名 ) ,对照组 110名 (男 5 6名 ,女 5 4名 ) ,进行为期 2年的补钾补钙干预对照试验。干预组及其共同生活的家庭成员每人每天补充钾和钙各 10mmol,与食盐混合在一起。结果　经2年期试验 ,补钾补钙组夜 12h尿中K+含量为 ( 4 8± 2 3 )mmol,尿Na+含量为 ( 6 2 4± 2 8 2 )mmol;对照组尿K+含量为 ( 7 8± 3 6 )mmol,尿Na+含量为 ( 71 8± 2 7 5 )mmol,两者比较 ,差异有显著意义。补钾补钙组血压较基线平均下降了 5 3/ 1 8mmHg ,对照组血压较基线上升了 1 3 / 1 7mmHg,二者比较收缩压相差 6 6mmHg ,舒张压相差 3 5mmHg。结论　在家庭日常食盐中适量添加钾和钙 ,可促进钠盐的排泄 ,降低血压偏高青年的动脉血压 ,是有效预防青年高血压的重要途径。     

Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats

Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10 mg/kg, subcutaneously [s.c.]; n = 8/dose), LY255582 (LY; 0.03-1 mg/kg, s.c.; n = 8/dose), or vehicle were injected 30 min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors.     

Effect of alcohol ingestion on portal venous blood flow in healthy volunteers: comparison between the subjects with and without ALDH I isozyme

Effect of alcohol ingestion (25 g ethanol) on portal venous blood flow was investigated in healthy subjects using an ultrasonic pulsed doppler method. It was found that; (1) portal blood flow increased by 24% at 30 minutes and returned to the basal level at 60 minutes after alcohol ingestion; (2) there was no significant difference in the effect of alcohol ingestion on portal blood flow between the subjects with and without ALDH I isozyme; (3) blood ethanol levels correlated with portal blood flow at 30 minutes after alcohol ingestion, while this correlation was not observed at 60 minutes thereafter; and (4) blood acetaldehyde levels did not correlate with portal blood flow either at 30 minutes or at 60 minutes following alcohol ingestion. In conclusion, the portal blood flow increases following alcohol ingestion which is not associated with the increase in the blood acetaldehyde level.     

汞对大鼠三叉神经节电压依赖性钙通道电流及[Ca2+]i的影响

目的 观察Hg2+对大鼠三叉神经细胞膜电压依赖性钙通道电流(Ica)及胞内游离Ca,2+浓度的影响,探讨汞对三叉神经细胞毒性作用的机制.方法 全细胞膜片钳方法记录不同剂量的H2+作用下三叉神经细胞膜Ica的变化,并用激光共聚焦和Fluo-3/AM荧光探针标记技术,从单个细胞水平检测H2+寸胞内游离Ca2+浓度瞬间动态变化的影响.结果 0.01、0.10、1.00、10.00μmol/L H2+可使三叉神经细胞Ica电流幅值分别减少(1.80±0.32)%、(23.04±9.46)%、(58.20±7.90)%、(82.00±5.77)%,给Hg2+5min之内抑制作用即可达最大效应,洗脱未见明显电流恢复.0.01、0.10、1.00μmol/LH2+可使三叉神经细胞游离Ca2+浓度即时增加(2.500±83)%、(82.81±35.36)%、(222.70±62.48)%;预先用10 μmol/Lnifedipine处理细胞10 min,可在一定程度上减弱Hg2+的升钙作用,并延缓升钙的时间.结论 Hg2+对神经细胞膜Ica幅度的抑制作用与H2+抑制电压依赖性钙通道有关;H2+导致的神经细胞内游离Ca2+度升高与细胞内钙库释放有关.     

Modulating effects of biogenic amines on calcium and ethanol-induced sleeping time

The present study was carried out in order to clarify the mechanism of calcium prolongation of ethanol-induced sleep. p-Chlorophenylalanine (PCPA, 300 mg/kg), alpha-methyltyrosine (alpha MPT, 100 mg/kg) and diethyldithiocarbamate (DDC, 250 mg/kg) were administered intraperitoneally (IP) to mice to reduce the levels of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) respectively in the brain. Sleeping time was then measured following the administration of ethanol (4.5 g/kg, IP) both with and without CaCl2 (20 mumol/kg, intravenous (IV)). When saline (IP) plus CaCl2 (IV) was administered, the duration of ethanol-induced sleep was prolonged by 100% as compared with saline (IP) plus saline (IV). Duration of ethanol-induced sleep was not changed by PCPA, alpha MPT and DDC. On the other hand, the prolongation of ethanol-induced sleep by CaCl2 was antagonized by PCPA, alpha MPT and DDC. Also, only the DA level in the cerebrum was increased by 25% by administration of CaCl2. We suggest that the increase in ethanol-induced sleeping time due to CaCl2 results from the increase in biogenic amines in the brain.     

The influence of the luteal and follicular phases on major pharmacokinetic parameters of blood and breath alcohol kinetics in women

Drink tests involving 14 women were carried out to determine the effects of the menstrual cycle phases on the pharmacokinetics of ethanol. One experiment was carried out in the follicular phase of the cycle and another in the luteal phase, with the estradiol, progesterone, and testosterone levels being determined in both cases. The target concentration was a final blood alcohol concentration (BAC) of approximately 0.08 g%. After drinking was completed, concurrent BAC and breath alcohol concentration (BrAC) measurements were carried out at intervals of 10-20 min. The ethanol elimination rate was determined by calculating a linear function in the part of the slope that was clearly linear. In addition, the c₀ and Widmark factors r were calculated.In 10 of the volunteers, who had a normal increase in progesterone in the luteal phase, the average hourly elimination rate ß₆₀ in the follicular phase amounted to 0.0194 ± 0.0020 g%/h (BAC) and 0.0975 ± 0.0068 mg/L/h (BrAC), and in the luteal phase to 0.0193 ± 0.0031 g%/h (BAC) and 0.1026 ± 0.0101 mg/L/h (BrAC). There was no significant difference. Other pharmacokinetic parameters (c₀ concentrations, Widmark factors r, distribution volumes, maximal BAC, mean absorption rate, time until the peak concentrations were reached) also revealed no significant differences between the blood and breath alcohol levels of the luteal and follicular phases. In addition, no significant correlations were observed between the absolute progesterone level and the respective elimination rates ß₆₀.     

Diverse effects of ethanol on Ca entry and subsequent aggregation of platelets

Although alcohol is known to inhibit platelet aggregation, and transplasmalemmal Ca²⁺ entry is profoundly involved in platelet aggregation, there has been limited knowledge about the relationship between alcohol and Ca²⁺ entry. The purpose of this study was to determine whether and how ethanol in vitro affects Ca²⁺ entry through different pathways and the subsequent aggregation of platelets. Thapsigargin, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and thrombin were used to stimulate human platelets. Ca²⁺ entry and the subsequent aggregatory responses of platelets were measured by spectrofluorometry using fura-2/AM as an indicator and the light transmission method, respectively. Thapsigargin-induced Ca²⁺ entry and the following platelet aggregation were significantly inhibited by ethanol at concentrations of 0.5% or more. OAG-induced Ca²⁺ entry was significantly augmented by ethanol at concentrations of 0.5% or more, whereas platelet aggregation by OAG was significantly inhibited by ethanol at concentrations of 0.5 % or more. Thrombin-induced Ca²⁺ entry was not significantly affected by ethanol up to 2%, whereas platelet aggregation by thrombin was markedly inhibited by ethanol at concentrations of 0.5% or more. Thrombin-induced Ca²⁺ entry in the presence of SKF-96365 was augmented by pretreatment with ethanol. Ethanol in vitro showed diverse effects on the different Ca²⁺ entry pathways of platelets, whereas aggregatory responses induced by activation of the different Ca²⁺ entry pathways of platelets were all inhibited by ethanol. These results suggest that ethanol inhibits platelet aggregation mainly via a mechanism(s) other than transplasmalemmal Ca²⁺ entry.     

Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: Assessment of the effects on first-pass metabolism of ethanol

Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mm NAD⁺. Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (K_is) ranging from 0.90 mm (ADH2) to 20 mm (ADH1A), and the intercept inhibition constants (K_ii) ranging from 1.4 mm (ADH1C allozymes) to 19 mm (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (K_is = 3.0 mm and K_ii = 2.2 mm), but competitive inhibition for ALDH1A1 (K_is = 0.96 mm). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2–0.5 mm) and physiologically relevant concentrations of ethanol (10 mm) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12–26%) and ADH2 (14–28%) in the liver and small intestine, ADH4 (15–31%) in the stomach, and ALDH1A1 (16–33%) and ALDH2 (8.3–19%) in all 3 tissues. The results suggest that inhibition by acetaminophen of hepatic and gastrointestinal FPM of ethanol through ADH and ALDH pathways might become significant at higher, subtoxic levels of acetaminophen.     

The effects of ethanol and naloxone on extinction of jump-up avoidance performance in rats

The present study assessed the effects of ethanol and naloxone on the extinction of a jump-up avoidance response in Sprague-Dawley rats. Rats were first trained to jump onto a shelf to escape or avoid shock (0.5 mA). Upon reaching an acquisition criterion of 8 consecutive avoidance trials, animals were removed from the apparatus and exposed to 1 of 4 doses of ethanol (0, 1.0, 2.0, or 2.5 g/kg), and either naloxone (3 mg/kg) or saline. Rats were then returned to the conditioning apparatus with the shock turned off, and resistance to extinction was assessed. Ethanol had biphasic effects with low doses (1 g/kg) facilitating, and higher doses (2 and 2.5 g/kg) suppressing number of extinction responses by comparison to controls. Naloxone did not influence the course of extinction, and did not reverse any of the effects of ethanol. These results did not support the hypothesis that the effects of ethanol on aversively-motivated behavior are opioid-mediated.     

Effects of ethanol administration on corticosterone levels in adolescent and adult rats

Adolescent humans and rodents have been shown to consume more alcohol than their adult counterparts. Given that corticosterone (CORT) has been shown to be related to the intake of several drugs of abuse, this study assessed the ontogenetic effects of low-moderate doses of ethanol on CORT increases and recovery. Despite no significant differences in baseline (home cage) CORT levels, CORT responses to ethanol were greater in females than in males and in adult females than in adolescent females; males, however, showed less marked age differences in CORT levels after ethanol consumption. Adolescent blood ethanol concentrations (BECs) were lower than those of adults, although these BEC differences appear insufficient to account for the ontogenetic differences in CORT levels. Collectively, these findings suggest that it is unlikely that age differences in CORT elevations provide a major contribution to the ontogenetic differences in alcohol intake seen between adolescents and adults.     

Application of a three-compartment model to a study of the effects of sex, alcohol dose and concentration, exercise and food consumption on the pharmacokinetics of ethanol in healthy volunteers

A recently developed three-compartment model for the absorption and elimination of ingested alcohol was applied to re-analyse a study on the effects of various factors known to influence the blood-alcohol curve. The absorption and elimination of alcohol after drinking diluted alcohol were studied in healthy volunteers under strictly standardized conditions. The factors studied were sex, dose, concentration, physical exercise, meal consumption before drinking, energy content and composition of the meal, and time of drinking in relation to meal consumption. Gastric emptying and absorption from the small intestine were assumed to be first-order, and a possible delay (or acceleration) of gastric emptying was accounted for by a feedback-control parameter. The elimination process was assumed to follow Michaelis-Menten kinetics. Clear effects were observed of sex and dose, and aspects of meal consumption on absorption and elimination of alcohol. The ingestion of a meal prior to the intake of alcohol reduced both the gastric emptying rate and absorption efficiency of alcohol, increased the gastric emptying delay and reduced the rate of elimination. The absorption efficiency was even lower when the alcohol was consumed during the meal instead of after the meal. Using alcohol during the meal accelerated gastric emptying and reduced absorption efficiency as well as rate of elimination. High-fat meals resulted in the highest gastric emptying rate and rate of absorption from the small intestine, whereas high-protein and high-sucrose meals resulted in the lowest gastric emptying rate. Simultaneous consumption of a high-sucrose meal and alcohol increased gastric emptying delay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of acute ethanol administration and chronic ethanol feeding on mixed function oxidation in deermice lacking ADH

Hepatic microsomes catalyze the oxidation of ethanol and other drugs. The mechanisms through which ethanol alters mixed function oxidation are still debated. There is evidence that ethanol and drugs interact at a microsomal level, but there are also claims that ethanol may interfere with drug metabolism indirectly by affecting the supply of NADPH through NADH production in the ADH pathway. To investigate the role of chronic ethanol consumption, deermice with normal liver ADH (ADH+) or genetically lacking ADH (ADH-) were pair-fed liquid diets containing ethanol or isocaloric carbohydrate for 23 days. The acute effects of ethanol were studied in deermice fed standard laboratory chow and tap water ad lib. In vivo and in vitro, the effects of an acute dose of ethanol and chronic ethanol feeding on mixed function oxidation as measured by the demethylation of aminopyrine were similar in both animal strains. Statistical analysis showed no significant differences between ADH+ and ADH- animals under all experimental conditions studied. We conclude that induction and inhibition of mixed function oxidation by ethanol may be related to the interaction of ethanol with hepatic microsomes rather than to redox changes produced by ADH mediated ethanol metabolism.