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C57BL/6J/BOM mice were given 15% (w/v) ethanol solution as their sole drinking fluid. Nerve conduction velocities (NCV) and motor coordination (ataxia) of the unanesthetized animals were examined after a single IP injection of 3.0 g ethanol/kg body weight at 6, and 9 months after the start of drinking and after 3 months of abstinence. During chronic consumption of ethanol, tolerance for relative conduction time (RCT) change developed in six months. This tolerance was not observed after 9 months of ethanol treatment. The tolerance for ataxia persisted throughout the period of ethanol treatment. After a three month's abstinence, no differences between the controls and the animals previously on ethanol were observed regarding responses to acute ethanol administration. These observations suggest that different mechanisms underlie the development of tolerance for the effect of ethanol on peripheral nerve conductance and for the ataxia from ethanol in the central nervous system.

Urinary excretion of estrogens and plasma concentrations of estrone, estradiol, LH, FSH, PRL, progesterone, testosterone, and sex hormone binding globulin were measured in nine chronic alcoholic women with cirrhosis or alcoholic fatty liver. They were aged 24-40 yr and all had secondary amenorrhea which had lasted for at least 3 months. The response of pituitary gonadotropin secretion to administration of LHRH and estradiol benzoate and of PRL secretion to TRH were also investigated. Urinary excretion of estrogens in the alcoholic women with liver disease was similar to that in normal postmenopausal women and less than half that in normal women of the same age in the midfollicular phase of the menstrual cycle. Plasma estradiol levels in the alcoholic women were lower than in the menstruating women but higher than in the postmenopausal women, whereas their plasma estrone levels were higher than in the menstruating women. Plasma concentrations of progesterone and testosterone in the alcoholic women did not differ from those in the postmenopausal women but were lower than in the menstruating women. In spite of the relative estrogen deficiency plasma LH and FSH levels were not elevated in the alcoholic women. The responses of LH and FSH to LHRH were similar in the patients and in the menstruating women. Intramuscular administration of estradiol benzoate did not increase plasma LH and FSH concentrations in the alcoholic women. Hyperprolactinemia was not found and there were no differences in the PRL responses to TRH between the patients and the control groups. In conclusion, disturbed regulation of gonadotropin secretion is an important factor in the genesis of estrogen deficiency and amenorrhea in alcoholic women with liver disease, although ovarian function may also be directly impaired.

The activities of the catecholamine-synthesizing and inactivating enzymes were determined in whole brains of two pairs of rat strains differing in their genetically-determined behavioural responses to ethanol. The alcohol-tolerant (AT) rats did not show any significant differences in enzyme activities when compared with the non-tolerant (ANT) strain. The activity of tyrosine hydroxylase was found to be significantly higher in brains of the alcohol-preferring (AA) rats, than in those of the alcohol-non-preferring (ANA) strain.

The effects of oral administration of xylitol on the rate of ethanol elimination and on the ethanol-induced changes in blood concentrations of lactate and pyruvate were studied in seven healthy male subjects. Xylitol (1.0 g/kg body weight) was administered orally and ethanol (0.8 g/kg body weight) intravenously. In the control experiments glucose was given instead of xylitol. Xylitol had no significant effect on the rate of ethanol elimination or on the ethanol-induced increase in the blood lactate concentration. The ethanol-induced changes in the lactate/pyruvate ratio were not affected by xylitol. It is suggested that the ineffectiveness of xylitol is due to its low concentration in the liver after oral administration. Ethanol induced a 5--10 fold increase in the blood concentration of xylitol. This is most probably due to inhibition of xylitol oxidation in the liver by the ethanol-induced reduction in the hepatic redox state. The clinical significance of this finding is unknown.

To elucidate the site of the ethanol-induced inhibition of the secretion of the growth hormone (GH) we studied the effect of ethanol on the growth hormone releasing hormone- (GHRH) stimulated secretion of GH in 9 healthy men, aged 22 to 41 years. After fasting over night the subjects received ethanol (1.0 g/kg of body weight) during 1.5 hours in the morning. Thereafter 100 micrograms of GHRH were given intravenously and the blood or serum concentrations of ethanol, glucose, GH, sometomedin C, free fatty acids and acetate were monitored for 4 hours. Every subject served as his own control by participating in an identical session during which water was served instead of ethanol. In 6 out of 9 subjects ethanol augmented the response of GH secretion to GHRH. Interestingly, serum concentrations of somatomedin C were higher after ethanol intake than without ethanol. Ethanol had no effect on blood glucose but serum concentrations of free fatty acids were lower and those of acetate higher during the ethanol session than in the control experiment. The results favour the suggestion that ethanol does not inhibit the GH release at the hypohyseal level. In contrast, ethanol may enhance the effect of GHRH, possibly through its influence upon serum levels of free fatty acids.

The effects of fructose and glucose on the metabolic changes induced by ethanol and on the intensity of alcohol intoxication and hangover were studied in 109 healthy male volunteers. After 10 hours of fasting, the subjects were given 1.75 g of ethanol per kg body wt during 3 hours under controlled laboratory conditions. Fructose or glucose were adminstered either simultaneously with ethanol or 12 hours later during the hangover period. The intensity of alcohol intoxication and hangover were estimated 10 times during the experimental period of 20 hours using subjective and objective rating scales. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids, triglycerides, ketone bodies and capillary blood acid-base balance were also made during the experiment. Under these experimental conditions neither fructose nor glucose had any significant effect on the intensity of alcohol intoxication and hangover. The sugars also had no significant effect on the rate of ethanol elimination or on the blood acetaldehyde concentration during the course of the experiment. Blood glucose concentration was decreased and blood lactate, free fatty acid and ketone body concentrations were increased during the hangover period in the subjects who had been given only ethanol. These subjects also had a marked metabolic acidosis during hangover. Glucose and fructose significantly inhibited the metabolic alterations induced by ethanol. In this respect fructose was more effective than glucose. The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover. The results support the view that hangover is not directly related to the metabolic effects of ethanol or to its metabolic products.

To determine whether acute ethanol administration affects the function of the adrenergic system the concentrations of plasma catecholamines and cyclic AMP (cAMP), the level of lymphocytic beta-receptors, the concentration of basal and isoproterenol-stimulated lymphocytic cAMP and the excretion of urinary catecholamine metabolites were studied in six healthy men. These parameters were also measured during the hangover, both under resting condition and during an anaerobic ergometer exercise. Acute intake of ethanol (1.5 g/kg body weight) had no statistically significant effect either on plasma adrenaline and noradrenaline concentrations or beta-adrenergic receptor levels. Ethanol consumption did neither change the urinary excretion of catecholamine metabolites (homovanillic acid, normetanephrine, metanephrine, and 3-methoxyhydroxymandelic acid). Exercise was associated with a 6-10-fold elevation in plasma adrenaline and noradrenaline concentrations and with a two- to threefold elevation on beta-adrenergic receptor levels. This effect of exercise was not modified by preceding alcohol intake and resulting hangover. These preliminary findings suggest that acute alcohol intake does not significantly alter the concentration and functioning of human beta-adrenergic receptors.

Seventeen young adult C57BL male mice were given 15% (w/v) solution of ethanol as their sole drinking fluid for seven to nine months. C57BL male mice given regular drinking water were used as controls. After decapitation samples from the livers and the sciatic nerves of the mice were processed for electron microscopy and morphometry. The ultrastructural analysis revealed slight alterations in the nerves of the ethanol-exposed mice. The changes were mostly in the Schwann cells. Pathological Schwann cell-axon relationships were also more abundant in the ethanol-exposed mice. The thickness distribution of the myelinated nerve fibers was similar in the exposed and the control mice. The transverse-sectional area of hepatocytes was greater in the mice on ethanol than in the controls. The volume density of lipid vacuoles of the liver cells was significantly increased in the mice treated with ethanol (p less than 0.001). The hepatic changes indicate a significant effect of ethanol on the liver. The findings suggest that, in mice, chronic peroral treatment with ethanol can produce slight changes suggesting peripheral neuropathy together with fatty metamorphosis of the liver.

727 consecutive drunken drivers were studied for laboratory markers of excessive alcohol consumption. Serum gamma-glutamyltransferase and alanine aminotransferase showed no differences and aspartate aminotransferase and blood alcohol concentration only small differences between groups of first and repeating drunk driving offenders. The best laboratory test to differentiate the repeating offenders with probably more serious alcohol problems from the first offenders was in our material serum acetate, the mean serum acetate level of the repeating offenders being highly significantly (P less than 0.001) higher than that of the first offenders or nonalcoholic controls. Serum acetate also differentiated first offenders from nonalcoholic controls (P less than 0.001). Our results suggest that serum acetate could be used for the screening of problem drinking among drunken drivers.

The serum concentration of selenium was decreased by 17 and 48% in non-cirrhotic and cirrhotic alcoholics, respectively, as compared to healthy controls. In these alcoholics the serum selenium correlated positively with the serum albumin and plasma prothrombin time and inversely with the serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase. Abstinence from ethanol for two weeks was without effect on the serum selenium level in non-cirrhotic alcoholics and acute alcohol intake did not change the serum selenium concentration in non-alcoholic volunteers. In patients with primary biliary cirrhosis the serum concentration of selenium was similar to that in the alcoholic cirrhotics. In patients with hypoalbuminaemia of renal origin the serum selenium was normal. In conclusion our results show that the deterioration of liver function, irrespective of its aetiology, leads to the decrease in serum selenium levels. Whether a defect in removal of lipoperoxides is associated with this decrease in serum selenium concentration remains to be decided by further studies.

The plasma or serum concentrations of testosterone, LH, FSH, PRL, cortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, estrone and estradiol were monitored in 8 healthy male volunteers for a period of 48 hr after administration of one large dose of ethanol (1.75 g/kg BW) within the first 3 hr of the experiment. Each subject served as his own control in an identical experiment without ethanol. Blood alcohol concentration reached a maximum of 1.51 +/- 0.08 g/l (mean +/- SEM) 4 hr after the start of drinking. The maximum decrease in serum testosterone was observed at 12 hr when the serum concentrations of gonadotropins were still unchanged. The decrease in serum testosterone persisted at 24 hr despite increases in the serum levels of LH and FSH. The serum or plasma concentrations of PRL, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone were clearly increased 4 hr after the start of drinking. The increase in serum cortisol lasted as long as the decrease in serum testosterone. No significant changes were found in plasma concentrations of estrone and estradiol. Our results suggest that in addition to direct testicular effects of alcohol, increased adrenal secretion of cortisol may contribute to the decrease in serum testosterone in men acutely intoxicated with ethanol.

We studied the potential contribution of acetate to the cardiovascular effects of ethanol in 12 healthy male volunteers. Sodium acetate, or sodium chloride in control experiments, was infused i.v. at the rate of 0.033 mEq/kg/min for 60 min. Left ventricular function was examined by M-mode echocardiography and systolic time intervals during infusion and for 60 min thereafter. Blood acetate rose during infusion from 0.19 +/- 0.02 (mean +/- SEM) to a maximum of 0.99 +/- 0.08 mmol/liter. Changes in serum free fatty acids, glycerol, and ketone bodies indicate that acetate inhibited peripheral lipolysis. The volume of urine excreted during the acetate experiment (305 +/- 37 ml) was significantly larger (p less than 0.01) than during the chloride experiment (181 +/- 21 ml). Left ventricular function did not differ between the experiments during the infusions even though at 45 min heart rate was increased by acetate (7%; p less than 0.01, between infusions). After the infusion period, at 75 min the treatment by acetate increased cardiac output from the baseline by 17% (p less than 0.05, between infusions), and decreased peripheral arterial resistance (19%, p less than 0.05), and diastolic blood pressure (10%, p less than 0.01). Circumferential fiber shortening velocity was increased during the acetate experiment maximally by 7% (p less than 0.01) from the baseline at 120 min. These data indicate that acetate is an arterial vasodilator and a mild diuretic and may slightly improve myocardial performance in the concentrations encountered during ethanol metabolism in men.

The effects of alcohol intake on serum lipids and lipoproteins depend on the dose and mode of alcohol intake, individual susceptibility, genetic variables, and dietary factors. Therefore the changes of lipoprotein pattern are different among moderate and heavy drinkers. Moderate intake of alcohol increases the concentrations of apolipoproteins (apo) AI, apo AII, and high-density lipoprotein subfraction (HDL3) in plasma without any effects on other lipoproteins. If alcohol intake exceeds 60 to 80 gm per day, the synthesis of very low-density lipoprotein (VLDL) particles is stimulated. Even short-term use of alcohol stimulates lipoprotein lipase (LPL) activity in adipose tissue, and consequently the concentration of VLDL in plasma stays normal or is even subnormal. If alcohol intake continues in excessive amounts, the increased transport rate of VLDL particles as a result of high LPL activity results in the up regulation of HDL2. This is clearly evident in chronic alcoholics. Low or subnormal low-density lipoprotein (LDL) levels are another characteristic of the lipoprotein pattern in chronic alcoholics. The increase of HDL (HDL2) and reduction of LDL levels could well explain the reduced risk of coronary heart disease in chronic alcoholics, whereas the causal factors remain open among moderate drinkers.

Effect of ethanol on adenosine 3', 5' cyclic monophosphate (cAMP), calcium (Ca) and magnesium (Mg) excretion was studied in controlled clinical conditions in man. Seven male volunteers served as their own controls. In 5 subjects cAMP excretion was primarily suppressed by ethanol. Ethanol appeared to have a biphasic effect on Ca excretion, an initial stimulation followed by a conservation phase. Mg excretion was stimulated by ethanol in 5 subjects. Subjects having nausea and vomitus and the most severe hangover symptoms had the lowest urinary Ca excretion and the lowest imitial cAMP excretion. Ca and Mg metabolism and the susceptibility of the body to the toxic effects of ethanol appeared to be interrelated.

The effect of ethanol intoxication and hangover on immunoreactive plasma arginine vasopressin (AVP) concentration was studied in 7 healthy supine men in controlled clinical conditions. In 6 subjects plasma AVP increased above control values at the time of maximal blood ethanol concentration. The highest AVP values were observed in the subjects having nausea and vomiting and the worst hangover symptoms. During hangover plasma AVP values were higher than the controls and the response of plasma AVP to upright posture was exaggerated. The dissociation of plasma AVP concentration and ethanol diuresis suggested that the suppression of AVP release is not the sole determinant of ethanol diuresis. The study may indicate that the toxic effects of ethanol and the severity of hangover symptoms are associated with the state of hydration and individual sensitivity of AVP triggering mechanisms.

We examined the acute effect of moderate ethanol administration (oral and iv) on the counterregulatory response and recovery from insulin-induced hypoglycemia after an overnight fast in eight normal men, aged 26 +/- 6 yr. While ethanol increased fasting plasma glucose and serum insulin concentrations, after insulin administration plasma glucose concentrations fell to similar nadirs in the ethanol [2.5 +/- 0.2 (+/- SE) mmol/L] and control studies (2.3 +/- 0.1 mmol/L). The hypoglycemia-induced serum GH, cortisol, and glucagon responses were all reduced (P less than 0.05-0.005) during the ethanol study, while the rises in plasma epinephrine and norepinephrine concentrations were similar in both studies. After discontinuation of the insulin infusions, the initial recovery from hypoglycemia occurred sooner in the presence than in the absence of ethanol. These data indicate that ethanol facilitates the recovery from insulin-induced hypoglycemia in the face of reduced counterregulatory hormones responses. Thus, other mechanisms, such as ethanol-induced insulin resistance, may be important in facilitating the recovery from insulin-induced hypoglycemia during ethanol administration.

The hypolipidaemic effect of a new drug, gemfibrozil (CI-719), was studied for 20 weeks in 20 patients with primary type IIb, III, IV or V hyperlipoproteinaemia. Baseline recordings of serum cholesterol (9.1 mmol/l), triglyceride (3.79 mmol/l) and ultra-centrifugally isolated lipoproteins were obtained during a six-week pretreatment period with stable diet and body weight. With 800 mg of gemfibrozil per day given in two divided doses, the mean serum triglyceride and cholesterol levels were decreased by 44.6% and 10.5% respectively, during 20 treatment weeks. Only 2 patients were completely resistant to the hypolipidaemic action of the drug. Serum triglyceride was brought down to normal levels in 9 subjects. After 12 weeks of treatment the mean VLDL-triglyceride, VLDL-cholesterol, and LDL-triglyceride were reduced by 48.5%, 57.6%, and 22.7% respectively, while the HDL-cholesterol rose by 16%. The LDL-cholesterol increased slightly but significantly during treatment in type IV patients and decreased in type IIb patients. The change of LDL-cholesterol showed an inverse correlation with the initial LDL-cholesterol level (r=-0.87). The postheparin plasma lipoprotein lipase and hepatic lipase activities, determined separately by an immunochemical method, increased during four weeks of gemfibrozil treatment (+18.1% and +20.6% respectively), but neither of these changes was significantly correlated with the changes in any of the serum lipid or lipoprotein levels. Oral glucose tolerance was not influenced by the treatment, but one-hour plasma insulin increased slightly during administration of the drug. One patient discontinued the drug after eight weeks because of generalized allergic eczema, but no other side effects were recorded. It is concluded that gemfibrozil is highly effective in reducing elevated serum VLDL levels. The simultaneous elevation of LDL in type IV patients needs more attention and study. The mechanism of the hypolipidaemic action of the drug is so far obscure, but it might partly be due to an increased efficiency in VLDL removal by an increased activity of lipoprotein lipase.

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.

The endocrine effects of alcohol are briefly reviewed. Alcohol enhances glucose-induced insulin secretion and may thus cause reactive hypoglycemia. However, inappropriate insulin secretion is not the reason for alcohol-induced hypoglycemia in fasted subjects. The direct effects of alcohol in thyroid function in humans are small, although alcoholics often have low concentrations of thyroid hormones in their plasma because of liver damage. Alcohol increases cortisol secretion from adrenal cortex either by increasing ACTH secretion or, more probably, by directly stimulating the adrenals. Alcohol also increases aldosterone secretion. The production of epinephrine and norepinephrine by the adrenal medulla is increased during alcohol intoxication and withdrawal. Plasma testosterone concentration is decreased during hangover and during alcohol withdrawal. The decrease is due to direct effects of alcohol on the testes, because plasma LH concentration is increased simultaneously. Alcohol has no significant effect on the LRH-induced secretion of LH. Plasma growth hormone concentration is decreased during alcohol intoxication and increased during hangover. TRH-induced secretion of prolactin is increased during alcohol intoxication and inhibited during hangover and withdrawal. The last finding suggests that there is dopaminergic overactivity in hypothalamus during alcohol withdrawal.

The EEG was recorded in 27 subjects during hangover. Male healthy volunteers drank 1.75 g/kg body weight of ethanol in 3 h and the EEG was recorded 14-16 h later when the degree of hangover was highest. For control purposes a second EEG was recorded after a similar session when subjects drank water instead of ethanol. A third record was taken in normal laboratory conditions. T5-A1 and O1-A1 derivations were subjected to computer analysis from which spectral and frequency parameters were calculated. Visual analysis of the EEG during hangover showed a decrease and slowing of alpha activity and an increase in theta activity. Spectral analysis of the EEG gave a statistically significant increase in 7-8 c/sec activity during hangover. The EEG change could not be explained in terms of blood alcohol level, hypoglycaemia or acidosis. Also fatigue could be excluded as a cause of EEG change by means of "water controls". The conclusion is that the slowing of the EEG during hangover is caused by the depressant action of ethanol, or its metabolites, on cortical function.

Serum dolichol levels were studied in 95 active alcoholics and 16 abstinent alcoholics (at the time of blood sampling) and compared to those of 41 social drinkers. Active alcoholics had a significantly higher mean serum dolichol concentration (182.7 +/- 5.1 ng/ml, p less than 0.001 than either abstinent alcoholics (138.7 +/- 5.4 ng/ml) or social drinkers (142.1 +/- 4.1 ng/ml). During weekend (48 hr) heavy drinking (5.5 g of alcohol per kg b.w.) no significant changes were seen in mean serum dolichol concentrations in 10 healthy, nonalcoholic volunteers. Neither did moderate drinking for 10 days (60 g of alcohol daily)--preceded and followed by a period of abstinence--produce any significant changes in serum dolichol levels in 10 nonalcoholic subjects. During detoxification treatment of 12 alcoholics, mean serum dolichol concentration stayed constant for the first 7 days; on entering treatment it was 227.7 +/- 15.0 ng/ml, on the 3rd day 238.5 +/- 15.9 ng/ml, and on the 7th day of treatment 222.6 +/- 18.6 ng/ml. Our results show that as well as increasing urinary dolichol excretion, chronic alcohol abuse also produces increased serum dolichol concentrations. However, contrary to urinary dolichols, serum dolichol levels do not react significantly to heavy drinking lasting for 48 hr in nonalcoholic volunteers. Furthermore in alcoholics increased serum dolichol concentrations do not decrease as rapidly during abstinence as urinary dolichol concentrations do.

To evaluate the hemodynamic changes related to alcohol flush, the effects of ethanol intake (0.5 g/kg) were studied by echocardiography and systolic time intervals in 10 Finnish and 9 Japanese healthy volunteers. In 5 Japanese subjects, post-drink facial flush was associated with elevated blood acetaldehyde (peak levels 20-83 mumol/l) and marked cardiocirculatory stimulation. Heart rate was increased directly post ingestion by 65% (p less than 0.01), stroke index by 23% (p less than 0.05), and cardiac index by 106% (p less than 0.05). Diastolic blood pressure was simultaneously decreased by 23% (p less than 0.05), peripheral vascular resistance by 54% (p less than 0.01), and circumferential wall stress by 22% (p less than 0.05); ejection fraction was raised by 26% (p less than 0.01). The other Japanese and the Finnish subjects had no detectable acetaldehyde in blood after ethanol ingestion. The average hemodynamic alterations in them were similar in direction to the changes presented above, but quantitatively 6-10 times smaller (p less than 0.005 for each of these variables). Thus, in Orientals with genetically defective acetaldehyde oxidation, ingestion of even small amounts of alcohol evokes intense enhancement of left ventricular function, probably because of acetaldehyde-induced catecholamine release and peripheral vasodilation.

The effect of ethanol intoxication and hangover on plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) concentrations was studied in 7 healthy supine men in controlled clinical conditions during 18 h beginning at 6 p.m. Large individual variation was observed in the response of PRA, PA and PC to ethanol. Following ethanol, stimulation of PRA was observed at the 14th and the 16th hour (P less than 0.05), of PA at the 4th and the 6th hour (P less than 0.01 and P less than 0.05, respectively) and of PC at the 4th and the 14th hour (P less than 0.01 and P less than 0.05, respectively). Ethanol ingestion suppressed PC during the first hour (P less than 0.02). Water ingestion at 8 a.m. suppressed PA between the 14th and the 16th hour (8-10 a.m.) in control and ethanol experiment (P less than 0.01 and P less than 0.005, respectively). There was a dissociation between PRA and PA, but intra-individually PRA and PA correlated fairly or well. Plasma arginine vasopressin (AVP) and PC were also significantly correlated. The results suggest that changes in PA and PC as well as the dissociation of PRA and PA after ethanol ingestion might be partly related to dehydration and to the increased secretion of hypothalamic and pituitary hormones as well as to sodium and potassium balance. There was a biphasic effect of ethanol, including an inital suppression of PC and a subsequent increase of PC, PRA and PA. Upright posture appears to exaggerate the stimulating effect of ethanol on PRA, PA and PC.

The effects of different doses of clofibrate and gemfibrozil on liver size, serum triglyceride concentration and the activities of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and carnitine acyltransferases were studied in male rats. Both clofibrate and gemfibrozil treatment effectively decreased the fructose-induced hypertriglyceridaemia and increased the liver to body weight ratio. Clofibrate treatment also induced an increase of many times in the activities of mitochondrial alpha-GPD and carnitine acyltransferases, the effect increasing with the dose used. The effect of gemfibrozil on the activities of the enzymes was significantly smaller. There was no correlation between the decrease in serum triglyceride concentration and the changes in the activities of the enzymes. Only clofibrate increased the rate of fatty acylcarnitine oxidation in isolated mitochondria. It is concluded that both drugs increased the size of the rat liver, but that only clofibrate influenced the mitochondrial enzyme activities of mitochondrial carnitine acyltransferases and the accelerated mitochondrial oxidation of fatty acids are not the mechanisms by which these drugs lower serum lipid levels.

Acute effects of ethanol ingestion (1.0 g per kg body weight) on the serum levels of LH, FSH and prolactin were studied in 10 postmenopausal women. Ethanol was administered during the first 3 hr of the experiment and the hormone concentrations were monitored for 10 hr. Each subject served as her own control in an identical experiment without ethanol. Blood alcohol concentration reached its maximum 1.18 +/- 0.02 g/l (mean +/- S.E.M.) 3hr after the start of the drinking. No changes were found in the levels of LH and FSH during the experimental period. The increase of 80% in the mean concentration of prolactin at 4hr after the start of drinking was not statistically significant. On the basis of these and previous results we conclude that alcohol has no acute effects on the secretion of gonadotropins in women.

The plasma or serum concentrations of GH, TSH, LH, PRL, testosterone, cortisol, T4, and T3, and the values of the T3 uptake test were monitored in 12 healthy male volunteers for a period of 20 h after administration of one large dose of ethanol (1.5 g/kg BW). The effects of TRH and LRH on the secretion of TSH, PRL, and LH were studied in these subjects once during the period of acute alcohol intoxication (4 h after the start of drinking) and once during the hangover period (14 h after the start of drinking). Each subject served as his own control by drinking water only during another experimental session. Alcohol had no significant effect on basal concentrations of GH, TSH, LH, T4, T3, or testosterone. The concentration of cortisol in plasma was elevated during the whole 20-h period after ingestion of alcohol, as compared with the control values. Alcohol also did not significantly alter the effects of TRH and LRH on plasma TSH and LH levels at 4 and 14 h. During the hangover period, the PRL response to TRH was totally blocked, but during alcohol intoxication, there was a slight increase in the PRL response to TRH. The lack of response of PRL to TRH during the hangover suggests that withdrawal symptoms are associated with increased dopaminergic activity in the hypothalamus.

To study the relation between blood and liver selenium levels in hepatic disorders we measured the selenium concentrations of whole blood, serum and liver tissue obtained at laparoscopy in 17 patients with different kinds of liver diseases. As compared to healthy controls the mean concentration of selenium was decreased by 24% (p less than 0.001) in the whole blood of the patients (n = 15). Similarly, the mean concentration of selenium in serum was 35% lower in the patients than in the controls (p less than 0.001). As compared to the control samples obtained at autopsy the selenium content of liver was decreased by 13% (p less than 0.05) in the patients. Significant positive correlations were found between the selenium content of the liver and the whole blood (r = 0.62, p less than 0.05) as well as also between liver and serum (r = 0.52, p less than 0.05) selenium concentrations. In conclusion, the present study suggests that in patients with liver disorders the selenium concentrations are decreased not only in the blood but also in the liver tissue. Whether this means a decreased activity of hepatic glutathione peroxidase and, further, an increased possibility of oxidative cell injury, remains open.

To investigate the effects of acute ethanol administration on the production of proaggregatory thromboxane A2 (TxA2) and antiaggregatory prostacyclin (PGI2), ethanol (1.5 g/kilogram body weight) was given to eight healthy nonsmoking men, and the stable metabolites thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), respectively, measured by radioimmunoassay from serial blood samples before drinking and during the ensuing 18 hours. Each subject was studied as his own control on another occasion when only an equivalent volume of water was given. Serum TxB2 level decreased (p less than 0.01) from 206 +/- 31 ng/ml (mean +/- S.E.) to 167 +/- 24 and 161 +/- 23 ng/ml (two and four hours after beginning of the drinking, respectively) concomitantly with the attainment of maximal blood ethanol concentrations (about 120 mg/100 ml), whereas no changes occurred in plasma 6-keto-PGF1 alpha concentrations. Our results may provide an explanation for known effects of ethanol on platelet aggregation. They also raise speculation whether TxA2-inhibition and the antiatherogenic effect of alcohol intake are somehow related.

The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentrations of metabolites in the pregnenolone in equilibrium testosterone pathway were determined in freeze-stopped testes in control rats and during ethanol intoxication (2 h after injection of 1.5 g ethanol/kg body wt). Ethanol lowered the mean testicular concentrations of testosterone (by 63-74%), androstenedione (49-81%), 17-hydroxyprogesterone (60-76%), progesterone (29-67%) and pregnenolone (12-25%). 4-Methylpyrazole had no effect on the ethanol-induced changes. The present results reveal no inhibition at the 17-hydroxyprogesterone----androstenedione----testosterone steps, but do not exclude inhibition before the step yielding pregnenolone and at the pregnenolone----progesterone----17-hydroxyprogesterone steps.