Serial determination of plasma ethanol concentrations in mice

A technique permitting the serial determination of plasma ethanol concentration (PEC) in mice is described. Samples of blood, 5 microliters in volume, are drawn from the infraorbital plexus. It was demonstrated that this source reflects the rapid dynamics of absorption and clearance after an intraperitoneal injection of ethanol. Samples taken from the tail showed a greatly delayed response and required 30 min to equilibrate with samples taken from the infraorbital plexus. The concentrations of ethanol were determined by gas chromatography. A precolumn removed the nonvolatile constituents thus permitting the injection of plasma directly into the instrument. The ratio of ethanol concentrations in red blood cells to plasma was found to be 0.62. This permitted the estimation of concentration of ethanol in whole blood: (1-0.38 H) X PEC; where H = the hematocrit.     

19F NMR studies of enflurane elimination and metabolism.

The elimination and metabolism of enflurane, a fluorinated ether anaesthetic, was studied by 19F NMR in vivo in both rat liver and brain as well as human body fluids. In the liver of thiobarbitone-anaesthetized rats the half-life for enflurane following exposure to 0.15% (v/v) for 30 min was 76 min but this could be decreased to 39 min by pretreatment of the animals with isoniazid (0.1% in the drinking water for 7 days), an agent known to enhance enflurane metabolism. In these animals the major organic metabolite difluoromethoxy difluoroacetate (DFMDFA) was also detected by 19F NMR in vivo. This metabolite was detected along with fluoride ion in rat and human urine and plasma by high resolution 19F NMR. Human urine also contained signals from a probable DFMDFA conjugate and unexpectedly from trifluoroacetate.     

Oxamniquine inhibits metabolism of caffeine, hexobarbitone and antipyrine in vivo in mice

Inhibition of hepatic metabolism of caffeine (as assessed from expiration of (14)CO(2) resulting from N-demethylation of (14)C-labelled caffeine), hexobarbitone (as assessed from sleeping times) and antipyrine (as assessed from expiration of I4CO2 resulting from the oxidation of "C-labelled antipyrine) was studied in male GB-1 mice administered a single SO mg kg-1 oral dose of the schistosomicidal drug oxamniquine. Metabolism of caffeine, catalysed by cytochrome P-4S0 1A2(CYP1A2), was inhibited most, while hexobarbitone and antipyrine metabolism were inhibited to a lesser, though significant, degree. These results indicate a need for further studies to investigate possible clinically relevant inhibition of hepatic drug metabolism by oxamniquine.     

Research advances in ethanol metabolism.

The pharmacokinetics of alcohol determines the time course of alcohol concentration in blood after the ingestion of an alcoholic beverage and the degree of exposure of organs to its effects. The interplay between the kinetics of absorption, distribution and elimination is thus important in determining the pharmacodynamic responses to alcohol. There is a large degree of variability in alcohol absorption, distribution and metabolism, as a result of both genetic and environmental factors. The between-individual variation in alcohol metabolic rates is, in part due to allelic variants of the genes encoding the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). This review summarizes recent developments in the investigation of the following influences on alcohol elimination rate: gender, body composition and lean body mass, liver volume, food and food composition, ethnicity, and genetic polymorphisms in alcohol metabolizing enzymes as well as in the promoter regions of the genes for these enzymes. Evaluation of the factors regulating the rates of alcohol and acetaldehyde metabolism, both genetic and environmental, will help not only to explain the risk for development of alcoholism, but also the risk for development of alcohol-related organ damage and developmental problems.     

Hepatotoxicity of ethanol in mice.

Mice continuously exposed to ethanol vapour (for up to 19 days) developed fatty change in the liver (from 2 days onwards) and lesions resembling those of alcoholic hepatitis in man (from 5 days onwards). They also showed biochemical evidence of liver cell damage. Sera from ethanol-treated animals contained immunoglobulins that bound to the hepatocytes of ethanol-treated but not of control animals suggesting that exposure to ethanol was followed by an immunological response to a hepatocyte neo-antigen. In addition, such sera were cytotoxic in an in-vitro assay, and on Sephacryl S-300 gel filtration the cytotoxic activity eluted together with albumin molecules.     

The influence of different glucose concentrations in haemodialysis solutions on metabolism and blood pressure stability in diabetic patients

In recent years the percentage of diabetic patients on haemodialysis has increased. Considering the high frequency of intradialytic hypotensive and hypoglycaemic episodes experienced by these patients, it was the aim of the present study to evaluate the influence of different dialysate glucose concentrations (5.5 mmol/L or 11 mmol/L) on blood pressure and glycaemic regulation, using special dialysis equipment - the GENIUS System. This cross-over, prospective and randomised study, total duration 14 weeks, included 20 diabetic patients on maintenance haemodialysis. Group 1: 9 patients dialysed using dialysate with a glucose concentration of 5.5 mmol/L and after 7 weeks switched to dialysate with a glucose concentration of 11 mmol/L. Group 2: vice versa. Results show a statistically higher number of patients with hypoglycaemic and hypotensive episodes using dialysate with a 5.5 mmol/L glucose concentration. Also, mean serum glucose values were higher during haemodialysis sessions with a glucose dialysate concentration of 11 mmol/L. There were no statistical differences between the groups in laboratory values, HbA1C, insulin doses or in anthropometric parameters. Our results suggest that fewer diabetic patients undergoing haemodialysis using a higher dialysate glucose concentration of 11 mmol/L have hypoglycaemic and hypotensive episodes. Since this dialysate glucose concentration had no influence on lipid or hepatic metabolism, anthropometric parameters and especially HbA/1C values in this short-term study, the long term examination of its effects is warranted.     

The influence of ethanol and magnesium on aminoacyl-tRNA synthetases activity in rat's liver.

Ethanol exerts various influences on living organisms. Experiments were conducted in order to determine the influence of ethanol and magnesium on the aminoacyl-tRNA synthetases (aaRS) activity in rat's liver. The experiment was conducted on white Wistar rats of both sexes. The animals were divided into groups of 10 rats each. They received ethanol in their drinking water for 6 weeks. The first group received 5 per cent ethanol, the second received 20 per cent ethanol, the third received 20 per cent ethanol and 200 ppm magnesium, the fourth was the control and received water. After the duration of the experiments the animals were sacrificed using ketamine and the livers were harvested for further testing. Aminoacyl-tRNA synthetases were obtained by salting out with ammonium sulphate. The aminoacyl-tRNA synthetases activity were tested in vitro by using marked amino acids. Ethanol influences aminoacyl-tRNA synthetases activity. The influence of ethanol on the activity of aaRS depended on the size of the dose of ethanol taken by examined animals. At the same time it was revealed that magnesium supplementation limits the negative effect of high ethanol doses.     

Embryopathic effects of ethanol and caffeine in the chick

The combined effects of ethanol (20 and 40%, 0.1 ml/egg) and caffeine (0.5 and 1 mg/egg) on early chick embryos were investigated. After treatment with 0.5 mg caffeine and 20% ethanol at 48 h incubation, teratogenicity was potentiated, but without affecting embryonic growth. Embryotoxic interactions of this nature might account for congenital defects of doubtful etiology.     

The metabolism of nucleic acids in mice.

The metabolism of three forms of nucleic acid, native-DNA (N-DNA), single strand DNA (SS-DNA), and polyinosinic-polycytidylic acid (poly I : C), was investigated in vivo in randomly bred Swiss-Webster mice. Clearance of these substances from the circulation and tissue localization were determined at selected time intervals following the intravenous injection of 125I-labelled compounds. N- and ss-DNA were removed from the circulation more rapidly than was poly I : C. All three materials localized principally in reticuloendothelial-rich organs, i.e. liver and spleen. N-DNA was degraded by the liver more slowly than was poly I : C or ss-DNA. At 4 h following injection, the liver contained 26%, 13%, and 10% of the injected doses, respectively. Three days after injection, 4.5% of the N-DNA persisted in the liver, as compared to only 0.6% of the poly I : C, and 0.2% of the ss-DNA. The possiblity that these differences in metabolism of N-DNA, poly I: C, and ss-DNA may be related to their differing immunogenic potentials in experimental systems is discussed.     

The influence of semistarvation-induced hyperactivity on hypothalamic serotonin metabolism.

Male rats kept in a running wheel developed hyperactivity when food was restricted. Highest activity occurred around noon when food was given. Semistarved sedentary and ad lib fed sedentary and running rats served as controls. Five-hydroxyindole-acetic acid (5-HIAA) in the medial basal hypothalamus was lowest in the sedentary ad lib fed group. Running significantly increased 5-HIAA. Starvation likewise increased 5-HIAA. This effect was further enhanced by hyperactivity. When the circadian rhythm of serotonin (5-HT) and 5-HIAA was studied in the hypothalamus, a minimum of 5-HT as seen in semistarved sedentary and running rats around feeding time (noon). At this time 5-HIAA reached a maximum in the semistarved running rats while semistarved sedentary and ad lib fed rats showed no circadian pattern of 5-HIAA. These data indicate that serotonin turnover in the medial basal hypothalamus is increased as a consequence of semistarvation and hyperactivity.     

补骨脂素对骨质疏松小鼠骨代谢指标和生物力学的影响

目的利用卵巢切除小鼠模型,研究补骨脂素对骨质疏松小鼠骨代谢指标和股骨生物力学的影响。方法 40只雌性C57BL/6小鼠随机分为4组:假手术组(不切除卵巢+生理盐水),模型组(切除卵巢+生理盐水),雌二醇组(切除卵巢+雌二醇),补骨脂素组(切除卵巢+补骨脂素)。给药6周后测定血清碱性磷酸酶、Ⅰ型胶原羧基末端肽和雌激素含量。利用3点弯曲实验对股骨生物力学进行检测。结果与模型组比较,补骨脂素组血清碱性磷酸酶水平升高,但无统计学差异,补骨脂素组和雌二醇组血清I型胶原羧基末端肽水平明显降低。雌二醇组血清雌激素水平较模型组明显升高,补骨脂素组血清雌激素水平仍保持较低水平,与模型组比较无统计学差异。与模型组比较,补骨脂素治疗组小鼠股骨的最大载荷,最大应力和弯曲弹性模量系数指标显著升高。结论补骨脂素作为一种天然植物雌激素可改善骨质疏松小鼠骨代谢指标和股骨生物力学性能。     

The influence of acute exercise on sleep following high caffeine intake

The purpose of this study was to examine the influence of vigorous acute exercise on nocturnal sleep that had been disrupted by high doses (1200 mg) of caffeine throughout the daytime. Eight moderately fit, young males with a history of moderate caffeine use completed four conditions in a within-subjects, counterbalanced design: 60 min of (i) cycling at 60% VO(2peak) or (ii) quiet rest following placebo consumption, (iii) cycling, or (iv) quiet rest following the consumption of a high dose of caffeine. Each condition was performed twice from 1615-1715 h and followed by all-night polysomnographic recording. Subjects consumed two blinded 200-mg capsules of either lactose placebo or caffeine upon awakening, at 1600 h, and 2 h before bedtime. State anxiety was assessed at bedtime. Criterion scores consisted of the mean data across the two days in each condition. Sleep data were analyzed using a condition (exercise versus quiet rest) by drug (caffeine versus placebo) repeated-measures ANOVA. Caffeine-elicited sleep disturbance that was less than previously reported. Exercise attenuated selected sleep disturbances to a small degree. In general, the effects of exercise on sleep were not greater following caffeine compared to placebo. Indeed, increases in slow-wave sleep after exercise were approximately 1/3 smaller following caffeine treatment compared to placebo.