Comparison of ethanol metabolism in male and female cynomolgus macaques (Macaca fascicularis)

The physiological consequences of drinking ethanol differ among men and women; however, the biological basis of this gender difference is unknown. Our study characterized sex-related blood ethanol concentration (BEC) 60 min postethanol administration and ethanol elimination rates in male and female monkeys and across the phases of the menstrual cycle. Subjects were male (n = 4) and female (n = 4) cynomolgus monkeys (Macaca fascicularis) with a history of ethanol exposure and maintained at a lean body weight by food restriction. On three separate occasions, each monkey was administered 1.0 g/kg ethanol intragastrically and blood samples (20 microl) were collected every 60 min over a 5-hr period. For females, three phases of the menstrual cycle were determined by the presence of menses and plasma progesterone levels. There was no effect of menstrual cycle on mean 60 min BECs or mean rates of elimination. Mean BECs 60 min after 1.0 g/kg ethanol were: males = 86 mg/dl (+/- 2; n = 4) and females = 82 mg/dl (+/- 5; n = 4). There was no effect of sex on the highest BEC measured, which occurred at the 60 min time point in all subjects. Female monkeys did have faster average rates of ethanol elimination [34 +/- 2 (mg/dl)/hr] compared with males [23 +/- 1 (mg/dl)/hr]. The sex differences in metabolism of ethanol found with the macaque monkey model correlates well with human subject studies and suggests this is an appropriate model to further explore gender differences in response to ethanol.     

Ethanol elimination in males and females: relationship to menstrual cycle and body composition

Ethanol pharmacokinetics were determined following oral ethanol, 0.5 gm per kg, in nine normal women and 10 normal men, and related to total body water measured by 3H-water dilution and body fat determined anthropometrically. Ethanol pharmacokinetics were similar in the females throughout the menstrual cycle. No variation was seen in mean peak blood ethanol concentration or elimination rate in the midfollicular (Days 8 to 10) and midluteal (Days 22 to 24) phases. Mean peak blood ethanol values were significantly higher in females (88 +/- 3 mg per 100 ml) than in males (75 +/- 4 mg per 100 ml) (p less than 0.05), and the mean area under the ethanol concentration-time curve was significantly greater in females (241 +/- 12 mg X hr per 100 ml) than in males (177 +/- 11 mg X hr per 100 ml) (p less than 0.001). There was no significant sex difference in mean ethanol elimination rates. The mean apparent volume of distribution of ethanol in female (0.59 +/- 0.02 liter per kg) was less than in males (0.73 +/- 0.02 liter per kg) (p less than 0.001). Both apparent volume of distribution of ethanol and area under curve were significantly correlated with total body water suggesting that the sex differences in ethanol pharmacokinetics were due to sex differences in body water content. The sex differences in ethanol pharmacokinetics may partly explain reports of male-female differences in the natural history of certain ethanol-related disorders.     

Lactulose reduces intracolonic acetaldehyde concentration and ethanol elimination rate in rats

BACKGROUND: Normal colonic bacteria possessing alcohol dehydrogenase activity can oxidize ethanol to acetaldehyde. Acetaldehyde recently has been shown to be a local carcinogen in humans. The aim of the study was to examine the effect of lactulose feeding on fecal and cecal pH, intracolonic acetaldehyde concentration, and total ethanol elimination rate in rats. METHODS: Sixty Wistar rats were divided into four groups. Groups 2 and 4 received lactulose daily (11 g/kg body weight for 14 days). On days 7 and 14, groups 1 and 2 received ethanol (1.5 g/kg body weight) intraperitoneally, whereas groups 3 and 4 received saline. RESULTS: Fecal and cecal pH values decreased significantly after lactulose treatment compared with the controls. Lactulose feeding reduced the total ethanol elimination rate by 13.8% (257 +/- 0.008 mg/kg/hr vs. 298 +/- 0.003 mg/kg/hr, p < 0.001) and the intracecal acetaldehyde concentration by 66.2% after ethanol (49 +/- 29 microM vs. 145 +/- 47 microM, p = 0.03) compared with the controls. CONCLUSION: Lactulose feeding to rats significantly reduces ethanol elimination rate and intraluminal acetaldehyde concentration in the colon after ethanol administration. This prebiotic thus could be used as an effective agent to block the microbial production of carcinogenic acetaldehyde in the large intestine.     

Gender differences in alcohol metabolism: Relationship to liver volume and effect of adjusting for body mass

Background & Aims: Alcoholic liver disease purportedly develops more readily in women than in men. Some studies have demonstrated faster rates of alcohol elimination in women. This study examined whether gender differences in alcohol metabolism are related to differences in liver volume and/or differences in lean body mass. Methods: Ten men and 10 women had alcohol elimination rates determined by clamping of the breath alcohol concentration at 50 mg/dL by means of a constant rate of intravenous infusion of 6% ethanol. Liver volume was determined by computed tomography. Results: Mean alcohol elimination rate and mean computed liver volume were not significantly different in men and women. Lean body mass was 42% greater in men than in women. Consequently, the calculated alcohol elimination rate and liver volume per kilogram of lean body mass were 33% and 38% higher in women than in men, respectively. When the alcohol elimination rate was calculated per unit liver volume, no gender-related difference was found. Conclusions: Women have greater clearance of ethanol per unit lean body mass, confirming previous oral alcohol administration studies. Women have approximately the same liver volume as men, explaining the equivalent alcohol elimination rates seen when men and women are compared on the basis of liver size.GASTROENTEROLOGY 1998;115:1552-1557     

Influence of male hormones on rates of ethanol elimination in man

The effect of a reduction in androgens on ethanol elimination was determined in man. Bilateral therapeutic orchiectomy in nine patients for prostatic carcinoma decreased mean plasma testosterone levels from 489.8 +/- 31.2 (S.E.) ng per dl to 55.3 +/- 3.8 ng per dl and resulted in an increase in the rate of ethanol elimination in seven patients, no change in one, and a decrease in one. The mean rate of ethanol elimination for all nine patients increased from 83.6 +/- 4.0 to 100.4 +/- 4.2 mg per kg body weight per hr (p less than 0.02). The most likely mechanism for an increase in ethanol elimination after orchiectomy is an increase in liver alcohol dehydrogenase content, which remains to be demonstrated in man.     

Circadian and Genetic Effects on Ethanol Elimination in LS and SS Mice

Behavioral studies using mice have suggested circadian influences on response to ethanol. Studies examining possible circadian influences on ethanol elimination are ambiguous as to whether changes in elimination contribute to circadian variations in response. Therefore, the linear declines in blood alcohol concentrations (BACs) were assessed in long-sleep (LS) and short-sleep (SS) male mice at 0300, 0900, 1500, or 2100 hr following an intraperitoneal injection of either 2.5 or 4.1 g/kg ethanol. Overall mean BAC for LS mice was significantly higher than for SS mice at both ethanol doses. With the 4.1 g/kg dose, LS mean BAC was higher at 2100 hr than at 0900 hr. Both lines of mice exhibited faster elimination rates at 0300 and 0900 hr than at 1500 and 2100 hr. SS mice generally showed a more rapid decline in BAC than did LS mice at this dose. With the 2.5 g/kg dose, the rate of decline was faster at 0900 hr than at 2100 hr for both lines of mice. SS mice showed a significantly greater overall rate of decline than did LS mice. The line differences in blood alcohol concentration and elimination rate may have resulted from a change in the doses used to select these mice and may contribute to circadian influences on ethanol response.     

Oral fructose-induced changes in blood ethanol oxidokinetic data among healthy Nigerians

Reports on the influence of fructose on blood alcohol clearance have not always been consistent. Notwithstanding, information concerning the Nigerian population is yet to be documented. In this present study, ten consenting adults in apparent sound health, and who did not have any traceable history of alcohol or drug abuse were selected. The subjects were non-smoking Nigerians with an average age of 23.3 years and body weight of 55 kg, and were matched in body frame size and weight. The volunteers were given 0.55g (20%) ethanol/kg body weight as single dose about 4 hours after their breakfast meal, and on another occasion, 0.25g fructose/kg body weight was used to sober the intoxicating effect produced by 0.55g (20%) ethanol/kg body weight. In each case, the blood alcohol level (BAL) was determined every 30 minutes using about 0.5 ml whole blood obtained by venipuncture. The mean peak BAL obtained for the male and female subjects (0.093% vs 0.096%) imply that the women were more intoxicated, though for a shorter time (314 minutes vs 280 minutes). This investigation also demonstrates that the group of women cleared blood alcohol faster (0.026%/hr) and oxidized blood alcohol more rapidly (115.8 mg/kg/hr) than the men, who respectively recorded mean values of 0.021%/hr and 102 mg/kg/hr. However, among the male and female volunteers, oral fructose intake significantly (p<0.05) increased the blood ethanol clearance rate by 66.7 and 92.3%, decreased intoxication time by 41.7 and 40%, reduced peak BAL by 18.3 and 0%, but enhanced blood ethanol oxidation rate by 71.2 and 66.7%, respectively. The oxidokinetic data obtained suggest that Nigerian women may be more susceptible to alcohol's effects than Nigerian men, and oral fructose seems promising in the treatment of Nigerian alcoholics.     

Ethanol Metabolism in Women Taking Oral Contraceptives

The relationship between oral contraceptives and ethanol metabolism in women was examined in a group of 40 female social drinkers between the ages of 21 and 30. Twenty women taking oral contraceptives and 20 women not taking oral contraceptives were given a moderate dose of ethanol (0.52 g/kg) during the menstrual, intermenstrual and premenstrual phases of the menstrual cycle. The group of women taking oral contraceptives demonstrated a significantly decreased ethanol elimination rate (105 mg/kg/hr) than the women not taking oral contraceptives (121 mg/kg/hr, p less than .005). Ethanol disappearance rate also was significantly decreased for women taking oral contraceptives (0.015%/hr) than women not taking them (0.019%/hr, p less than .001). These results were consistent across the three phases of the menstrual cycle and when body leanness was taken into consideration. The decreased rate of ethanol metabolism in women taking oral contraceptives is consistent with reports of other drugs having decreased metabolic rates in women taking birth control pills. These results suggest that women taking oral contraceptives should be cautioned concerning their possible interaction with ethanol, as well as other drugs.     

Differences in body composition between Tongans and Australians: time to rethink the healthy weight ranges?

OBJECTIVE: The prevalence of obesity varies considerably between countries when compared using the common international standard. This study investigated body size and body composition in Tongan and Australian Caucasian adults. DESIGN: Cross-sectional comparative study. SUBJECTS: A total of 543 Tongans and 393 Australians. MEASUREMENTS: Weight, height, waist and hip circumference, four skinfolds, midarm circumference, elbow breadth, and body composition by bioelectrical impedance using sex- and ethnic-specific regression equations. RESULTS: Tongan women (mean body mass index (BMI)+/-s.e.=32.6+/-0.4 kg/m2) were larger than Australian women (BMI=25.8+/-0.4 kg/m2), with more fat-free mass (FFM; 52.2+/-0.4; 42.6+/-0.3 kg), fat mass (37.1+/-0.7; 26.6+/-0.8 kg) and percentage body fat (%fat) (40.5+/-0.4; 37.0+/-0.5%), respectively. Tongan men also had higher BMI (Tongan= 30.3+/-0.3 kg/m2; Australian=26.5+/-0.3 kg/m2), FFM (70.2+/-0.5; 62.3+/-0.6 kg) and fat mass (23.5+/-0.6; 20.7+/-0.7 kg). When compared with Australians within the same BMI range, Tongans had significantly higher FFM, elbow width, midarm muscle area and significantly lower %fat. The %fat at BMIs of 25 and 30 kg/m2 in Australian women was equivalent to the %fat found in Tongan women at 28.8 and 35.1 kg/m2, respectively. BMIs of 25 and 30 kg/m2 in Australian men corresponded with 27.5 and 35.8 kg/m2 in Tongan men. Skinfold thicknesses, waist, hip and WHR measurements suggested differences in fat distribution and body shape between ethnic groups, particularly in women. CONCLUSION: These results suggest that the standard healthy weight ranges recommended for international use may not be appropriate standards for use in the Tongan population.     

Skeletal muscle potassium increases after diet and weight reduction in obese subjects with normal and impaired glucose tolerance

Body composition calculated from total body potassium and skeletal muscle potassium were studied in middle-aged obese men and women with normal and impaired glucose tolerance as well as Type II diabetes before and after advice on calorie reduction during twelve months. The subjects were compared with healthy lean men and women. Mean weight loss was 6.6 kg (P less than 0.05). Lean body mass and body fat decreased 2.0 kg (P less than 0.05) and 4.6 kg (P less than 0.05), respectively. Total body potassium decreased by a mean of 146 +/- 49 mmol (P less than 0.01). Obese men with Type II diabetes and impaired glucose tolerance had lower total body potassium and muscle potassium levels than obese healthy men. After dieting, the obese men and women increased their muscle potassium levels with a mean of 2.8 mmol/100 fat-free dry weight to 42.6 +/- 2.6 mmol/100 g fat-free dry weight (P less than 0.05), but they were still below the levels of the lean controls, 44.4 +/- 1.3 MMOL/100 g fat-free dry weight, (P less than 0.01). Increase in skeletal muscle potassium was correlated to decrease in body weight, r = 0.55 (P less than 0.01) and to decrease in fasting blood glucose, r = 0.42 (P less than 0.05).     

Substantial weight gain during adulthood: the road to bariatric surgery

We sought to examine the relationship of body mass index (BMI) at age 18 years with the degree and rate of rise in body weight during adulthood among the morbidly obese. We evaluated 196 patients with a standard medical history form and a structured interview with questions regarding weight at age 18 years. The study included 40 (20.4%) men and 156 (79.6%) women. The mean BMI was 50.2+/-8.0 kg/m2, range 37.0-80.0 kg/m2. Based on self-reported weight, 133 (67.9%) were overweight/obese (BMI >25 kg/m2) and 68 (34.7%) were obese (BMI > or =30 kg/m2) at age 18 years. The distribution of cumulative weight gain was normal with a mean of 60.8+/-23.7 kg. There was a positive relationship (r=0.36, p<0.0001) between BMI at age 18 years and BMI in adulthood at a mean of 44+/-10.6 years. Independent predictors for cumulative adult weight gain were BMI at age 18 years (p<0.0001); women (p<0.0001); African Americans (p=0.05). These data suggest that modestly overweight young adults can have excessive weight gains during adult life, resulting in morbid obesity and high rates of obesity-related comorbidities.     

Exercise training improves fat distribution patterns in 60- to 70-year-old men and women.

Changes in body composition and fat distribution in response to endurance exercise training were compared in 47 men and 46 women, aged 60 to 70 yr. Body composition was assessed by hydrodensitometry and fat distribution was evaluated with skinfold thickness and circumference measures. The 9- to 12-mo exercise program consisted primarily of walking and/or jogging for 46 +/- 5 min.d-1, 4.0 +/- 0.6 d.wk-1, at 80 +/- 5% of maximal heart rate. Although men lost more weight during the exercise program than women (men, -3.4 +/- 4.4 kg; women, -1.6 +/- 3.8 kg), relative changes were not significantly different, averaging -3.7 +/- 4.1% and -2.7 +/- 2.9% of body weight in men and women, respectively. The changes in body weight reflected fat loss, as fat-free mass did not change. The reductions in skinfold thickness and circumferences were similar in men and women, and in both groups the largest absolute and relative changes occurred in the truncal area, indicating a preferential loss of fat from the central regions of the body. The results of this study indicate that endurance exercise training can favorably modify the abdominal fat distribution profile that is typical of older men and women in the United States and thus, perhaps, reduce the risk of the diseases associated with abdominal obesity.     

Nutritional Status and Body Fluid Distribution in Chronic Alcoholics Compared With Controls

BACKGROUND: At present few data are available on the total body water (TBW) content and in particular on the distribution of water in the intra- and extracellular compartments (ICW and ECW) of alcoholics. The aim of this study was to evaluate TBW, ICW, and ECW in chronic alcoholic patients. METHODS: Thirty-six alcoholics meeting DSM-III-R criteria for diagnosis (20 men, 16 women; body mass index [BMI] 22.3+/-2.57 kg/m2) were enrolled. Fifty-four healthy social drinkers (31 men, 23 women; BMI 23.7+/-1.68 kg/m2) matched for age and height were used as controls. Systolic and diastolic blood pressure was measured for all cases. All patients were assessed using specific anthropometric measurements. The waist-to-hip ratio (WHR) was used as an indicator of body fat distribution. TBW was measured by isotopic dilution by giving 100 microCi of tritiated water. ICW and ECW were assessed by multifrequence bioelectric impedance analysis (BIA). Basal metabolic rate (BMR) was measured by indirect calorimetry. RESULTS: Body weight was lower in the alcoholics than in the controls (61.9+/-5.5 kg vs. 65.8+/-5.2 kg;p < 0.01), essentially due to a reduction in fat mass. Significantly higher WHR values were found in both male (p < 0.001) and female (p < 0.001) alcoholics than in healthy subjects. A higher ECW/TBW ratio was found in the alcoholics compared with the controls, both as a whole (0.53+/-0.04 vs. 0.41+/-0.03; p < 0.0001) and separated by gender (p < 0.001). CONCLUSIONS: The increased ECW could derive from an increase in cellular permeability related to endothelial damage linked to the vasoconstriction present in the alcoholics and/or to a direct toxic effect of ethanol on cellular membranes. In addition, because the high ECW volumes correlated positively with WHR in the alcoholics, a potential association of these two factors in determining an increased risk of liver disease, hypertension, and cardiovascular disease may exist. Finally, the lower TBW characteristic of women may be one of the reasons for the observed greater rate of toxic effects of ethanol that occur in women.     

Concentration Dependency of Ethanol Elimination Rates in Baboons: Effect of Chronic Alcohol Consumption

Ethanol elimination rates were measured in 7 baboons fed alcohol for 2--7 yr (and their controls) by using a constant ethanol infusion to maintain blood ethanol at three different levels; 5, 10, and 50 mM. Ethanol elimination rates were significantly faster at a blood ethanol level of 50 mM than at 10 or 5 mM in both alcohol-fed and control animals. The difference between 50 mM and 5 mM concentration was 36% in alcohol-fed and 25% in control animals. In baboons fed ethanol chronically, the ethanol elimination rates were significantly faster than in pair-fed controls at 50 mM (179 +/- 10.0 mg/kg/hr versus 144 +/- 9.8) and at 10 mM (148 +/- 4.1 versus 114 +/- 8.2), but not at 5 mM. Even if one takes into account the extrahepatic losses, these differences cannot be explained solely by the elimination of ethanol through the low Km alcohol dehydrogenase pathway, and these observations indicate that a non-ADH system significantly contributes to ethanol elimination in vivo, especially in alcohol-fed baboons.     

Swift Increase in Alcohol Metabolism in Humans

One hundred and fifteen human male subjects, 19-30 years of age, received ethanol orally as vodka (0.55, 0.7, or 0.85 g/kg) followed by a second drink (0.3-0.4 g/kg) given 3-4 hr later. After both doses, blood ethanol levels reached approximately 100 mg/dl. Breath samples were taken every 20-30 min and rates of ethanol elimination were determined. In addition to the design described above, 100 subjects received 0.7 g/kg ethanol in two separate visits to the laboratory. In a third experimental design, ethanol was given i.v. to 12 subjects. With the single-day experimental design, the frequency distribution of changes in rates of ethanol elimination between the first compared with the second administration of ethanol was not unimodal. Up to 20% of the subjects demonstrated rates more than 40% greater than basal values in response to ethanol. Based on these findings in humans, a Swift Increase in Alcohol Metabolism (SIAM) was defined as an increase in the rate of ethanol elimination of at least 40% over the basal rate. Under these conditions, the frequency of SIAM was dose dependent (studied with 0.55, 0.7, and 0.85 g/kg); nearly 20% of the subjects demonstrated SIAM with a dose of ethanol of 0.85 g/kg. In the two-day experimental design, a SIAM response was also observed in about 10% of 49 well-fed subjects; however, none of 51 subjects tested exhibited a SIAM response following an overnight fast. In addition, a rapid and transient SIAM reflecting a 60% increase in the rate of ethanol elimination above basal values was observed when ethanol was given continuously for 5 hr i.v.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise test variables of a population with maximal bicycle exercise test

The aim of the study was to establish reference values for appraising the circulatory response of men and women to age-predicted maximal heart rate (220-age) exercise testing. The data of exercise testing have been analysed in 942 subjects (608 men and 334 women). Under exercise testing the mean maximal heart rate was 177/min in both sexes. Increase in heart rate per minute of exercise was 5.59 +/- 1.93 in men, 9.00 +/- 4.94 in women. At the peak of exercise test, systolic blood pressure was considerably higher in men than in women (188.96 +/- 27.98 vs. 171.66 +/- 28.46 mmHg; p much less than 0.0001). The average working capacity was 1.7 W/kg among men and 1.31 W/kg among women. The duration of exercise testing time was significantly longer in men than in women (918.6 + 269.4 vs. 578.4 +/- 193.2 s; p less than 0.0001). Reference values for testing time are given according to sex and age with due consideration of body weight and height.     

Validity of self-reported height and weight in a Japanese workplace population

OBJECTIVE: To assess the validity of self-reported height and weight in a Japanese workplace population, and to examine factors associated with the validity of self-reported weight. DESIGN: Comparison of self-reported height and weight with independent measurement. SUBJECTS: In total, 4253 men and 1148 women aged 35-64 y (mean measured body mass index (BMI): 23.3 kg/m(2) in men, 21.9 kg/m(2) in women) were included in the study. MEASUREMENTS: Self-reported height and weight were obtained by a self-administered questionnaire. Measured height and weight were based on annual health checkups. Sex, age, measured BMI, and the presence of hypertension, diabetes, and hyperlipidemia were examined as potential factors associated with the accuracy of self-reported weight. RESULTS: Self-reported height and weight were highly correlated with measured height and weight for men and women (Pearson's r for men and women: 0.979 and 0.988 in height, 0.961 and 0.959 in weight, 0.943 and 0.950 in BMI, respectively). For men, mean differences+/-2 s.d. of height and weight were 0.078+/-2.324 cm and -0.034+/-5.012 kg, respectively, and for women 0.029+/-1.652 cm and 0.024+/-4.192 kg, respectively. The prevalence of obesity with BMI > or =25 kg/m(2) based on self-reported data (23.6 and 11.5% for men and women, respectively) was slightly smaller than that based on measured data (24.9 and 12.4%, respectively). Specificity and sensitivity, however, were quite high for both men and women (sensitivity was 85.8 and 85.2%, and specificity was 97.0 and 98.9%, respectively). The subjects with higher measured BMI significantly underestimated their weight compared with those with smaller BMI after adjustments for age in men and women. Furthermore, the presence of diabetes in men and age in women affected self-reported weight. Neither the presence of hypertension nor hyperlipidemia was associated with reporting bias. CONCLUSION: The self-reported height and weight were generally reliable in the middle-aged employed Japanese men and women. However, it should be remembered that self-reported weight was biased by actual BMI and affected by age and the presence of diabetes.     

Effects of a 16-month randomized controlled exercise trial on body weight and composition in young,overweight men and women: the Midwest Exercise Trial

BACKGROUND: In light of the current obesity epidemic, treatment models are needed that can prevent weight gain or provide weight loss. We examined the long-term effects of a supervised program of moderate-intensity exercise on body weight and composition in previously sedentary, overweight and moderately obese men and women. We hypothesized that a 16-month program of verified exercise would prevent weight gain or provide weight loss in the exercise group compared with controls. METHODS: This was a randomized controlled efficacy trial. Participants were recruited from 2 midwestern universities and their surrounding communities. One hundred thirty-one participants were randomized to exercise or control groups, and 74 completed the intervention and all laboratory testing. Exercise was supervised, and the level of energy expenditure of exercise was measured. Controls remained sedentary. All participants maintained ad libitum diets. RESULTS: Exercise prevented weight gain in women and produced weight loss in men. Men in the exercise group had significant mean +/- SD decreases in weight (5.2 +/- 4.7 kg), body mass index (calculated as weight in kilograms divided by the square of height in meters) (1.6 +/- 1.4), and fat mass (4.9 +/- 4.4 kg) compared with controls. Women in the exercise group maintained baseline weight, body mass index, and fat mass, and controls showed significant mean +/- SD increases in body mass index (1.1 +/- 2.0), weight (2.9 +/- 5.5 kg), and fat mass (2.1 +/- 4.8 kg) at 16 months. No significant changes occurred in fat-free mass in either men or women; however, both had significantly reduced visceral fat. CONCLUSIONS: Moderate-intensity exercise sustained for 16 months is effective for weight management in young adults.     

In vivo interactions between H2-receptor antagonists and ethanol metabolism in man and in rats

The influence of a 7-day medication of either cimetidine (1,000 mg per day) or ranitidine (300 mg per day) on serum ethanol concentrations after a single oral dose of ethanol (0.8 gm per kg body weight) was investigated in a randomized placebo-controlled study in eight male volunteers. Compared with the placebo, cimetidine but not ranitidine produced a significant increase in both the peak serum ethanol concentration (85.9 +/- 3.5 vs. 73.0 +/- 3.2 mg dl-1, p less than 0.02) and in the area under the serum ethanol concentration time curve (350 +/- 19 vs. 304 +/- 25 mg dl-1 hr-1, p less than 0.05). However, the ethanol elimination rate was not affected by cimetidine. When ethanol (1.0 gm per kg body weight) was administered intravenously, cimetidine failed to induce a change in ethanol metabolism. Furthermore, the effect of H2-receptor antagonists was studied in animal experiments. Female Sprague-Dawley rats received a single dose of ethanol (7 or 3 gm per kg body weight) together with an intraperitoneal injection of either cimetidine (120 mg per kg body weight), ranitidine (120 mg per kg body weight) or isotonic saline. After alcohol absorption, ethanol elimination was significantly inhibited by both cimetidine (3.99 +/- 0.39 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) and ranitidine (4.21 +/- 0.14 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) at high ethanol concentrations (60 to 20 mM) but not at blood ethanol concentrations below 20 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sodium-lithium countertransport and hypertension in Rochester, Minnesota

The objectives of the present study were to determine whether increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370 +/- 147 [mean +/- SD] versus 315 +/- 110 mumol/l red blood cells [RBC]/hr, p less than 0.001) and in women (339 +/- 114 versus 269 +/- 92 mumol/l RBC/hr, p less than 0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (p less than 0.001) and 20.2% in women (p less than 0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p = 0.31) or in women (p = 0.29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354 +/- 139 versus 319 +/- 104 mumol/l RBC/hr, p less than 0.01) and in women (311 +/- 103 versus 278 +/- 83 mumol/l RBC/hr, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)