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Biomedical subjects

A W Chan

Publications and source records attributed to A W Chan.

At least 145 records · Page 8Linked to original sources
PubMed1987

Ethanol and chlordiazepoxide cross-dependence.

Cross-dependence between ethanol and chlordiazepoxide (CDP) was demonstrated by a bidirectional experiment involving induction of ethanol dependence in mice by a liquid diet method followed by substitution of ethanol with CDP. The administration of CDP diets fully suppressed ethanol withdrawal signs. After a period (14-24 days) of CDP administration the mice showed spontaneous CDP withdrawal signs following the termination of CDP diet. Similar signs, but much more short-lived, can also be precipitated by injection of the benzodiazepine receptor antagonist, RO-15-788.

Alcoholism↗
PubMed1986

Effect of glucose, NADH and NADPH on cortisol metabolism by mononuclear cells.

Mononuclear cell preparations are capable of metabolizing cortisol to three metabolites which lack the immunosuppressive effect of their precursor. In the present study we noted a linear correlation, up to a point, between glucose concentration and the rate of human mononuclear cell cortisol metabolism in vitro. The mechanism by which glucose exerts its effect was investigated further. We observed that: the effect of glucose on mononuclear cell cortisol metabolism was not influenced by insulin; NADPH and NADH enhanced cortisol metabolism by disrupted cells, irrespective of whether the homogenates were dialysed or not; lactate and ATP inhibited mononuclear cell cortisol metabolism and almost all the glucose used was converted to lactate. It is concluded that mononuclear cell cortisol metabolism can depend on both nucleotides.

Adenosine Triphosphate↗
PubMed1986

Racial differences in alcohol sensitivity.

The existence of racial differences in alcohol sensitivity between Oriental and Caucasian populations has been well documented. The primary manifestation is a highly visible facial flushing (47-85% in Orientals vs 3-29% in Caucasians) accompanied by other objective and subjective symptoms of discomfort. Even among different Oriental groups, subtle differences in the flushing response and alcohol consumption can exist. North and South American Indian populations differ in phenotypes for alcohol dehydrogenase and aldehyde dehydrogenase, but systematic studies comparing degree of flushing, alcohol elimination rates and blood acetaldehyde levels in these populations are lacking. Although flushing does not automatically 'immunize' an individual against alcohol use, those susceptible tend to consume less alcohol, at least in Orientals. However, the flushing phenomenon cannot be the sole explanation for differences in incidences of alcoholism among different racial groups. Socio-cultural, environmental and genetic factors also have to be considered. An increased incidence of flushing has been found to associate with a familial risk of development of future alcoholism in a Caucasian population. It remains to be determined whether the same is true in Orientals. Most biochemical investigations of the flushing phenomenon have focused on aspects of alcohol metabolism. Based on recent findings, a convincing mechanism is the higher accumulation of acetaldehyde in flushing subjects because they have an unusual, less-active liver aldehyde dehydrogenase isozyme (ALDHI). The possibility that an 'atypical' alcohol dehydrogenase, which is present in 85-90% of Oriental subjects, can contribute to increased blood acetaldehyde levels in flushing subjects cannot be ruled out. Based on results of a small number of pedigree studies which demonstrated familial resemblances in flushing, a pharmacogenetic defect in ALDHI has been proposed to be responsible for flushing. Other possible biochemical mechanisms (e.g. prostaglandins) and genetic defects need to be investigated.

Acetaldehyde↗
PubMed1984

Effects of combined alcohol and benzodiazepine: a review.

Both human and animal studies relating to the combined effects of alcohol and benzodiazepine (BZD) are reviewed. Although the combination of alcohol and BZD is sometimes associated with drug-induced deaths, drug overdoses and traffic accidents or fatalities, epidemiological information is lacking on the true extent of the combined abuse and on the patterns and prevalence of use of these two drugs. Since BZD are widely used for the short- and long-term treatment of alcoholics, these patients are deemed more at risk of developing BZD or alcohol/BZD dependence than the general population. There is a dire need for large-scale controlled studies concerning the efficacy of BZD in the long-term treatment of alcoholics. Compared to men, women are at a higher risk as far as the potential for BZD addiction is concerned, since they tend to use BZD more often. Epidemiologic studies on the patterns of use of BZD, alcohol or alcohol/BZD in pregnant women are called for. Animal models are also needed to ascertain whether prenatal exposure to both alcohol and BZD can impart long-lasting behavioral changes in the progeny. It is possible that BZD can exacerbate the damaging prenatal effects of alcohol.

Abnormalities, Drug-Induced↗
PubMed1983

Influence of chlordiazepoxide on alcohol consumption in mice.

In a free-choice situation, chlordiazepoxide (CDP; 12.5 or 25 mg/100 ml; groups B or C), when incorporated in ethanol solutions (2 to 20%, v/v), caused a significant decrease in ethanol preference index (P.I.). This was probably due to the combined CNS effects of both drugs rather than a taste effect, since the mice did not discriminate between aqueous CDP solutions and water. However, when the mice had prior exposure to ethanol and CDP was incorporated intermittently, no significant decreases in P.I. resulted. In a no-choice situation, ethanol intake was increased only on the first day of each intermittent incorporation of CDP (3 days for each 6-day cycle), being more persistent in group B (2 to 15% ethanol) than in group C (2 to 6.5%). Ethanol intake decreased in group C when alcohol concentrations exceeded 10%. The "first-day" CDP effect also occurred in the no-choice situation of an ethanolic liquid diet. Possible factors for this effect are discussed. Thus the effects of CDP on alcohol consumption in non-deprived mice vary with experimental designs.

Alcohol Drinking↗
PubMed1983

Long-lasting reduction in ethanol selection after involuntary intake of ethanol/chlordiazepoxide.

C57BL/6J mice, after having been exposed to a free-choice condition between water and aqueous chlordiazepoxide (CDP, 25 mg/100 ml) or between water and ethanol/CDP, showed a significant trend for decreased preference for ethanol when tested 2 weeks later. Similarly, mice previously exposed to a no-choice intake of ethanol showed a significant decrease in ethanol preference when tested subsequently. A long-lasting (greater than 20 weeks) reduction in ethanol selection developed after mice were previously exposed to ethanol/CDP in a no-choice condition. This was also accompanied by a decrease in the subsequent selection of ethanol/CDP, but not CDP. The exact mechanisms for the long-lasting decrease in ethanol selection was unknown, but it was not due to the development of fluid aversion. It is suggested that the combined central effects of ethanol/CDP might be partially responsible.

Alcohol Drinking↗
PubMed1983

An application of neutron activation analysis to small biological samples: simultaneous determination of thirty elements in rat brain regions.

Thirty elements in 7 rat brain regions were determined by instrumental neutron activation analysis (INAA). The samples were irradiated by thermal neutrons using 3 different sets of conditions, depending on the nuclear characteristics of the elements. Analysis of the resulting radionuclides was by gamma-ray spectrometry using a high resolution Ge(Li) detector and Nuclear Data 6600 multichannel analyzer, which was fully computerized to give quantitative results for the gamma-ray spectra. This paper demonstrates the use of INAA for small biological samples and to show its potential elements, 7 rat brain regions are listed. It is interesting to note that certain elements, e.g. fluorine and potassium showed high and low regional differences respectively, and hypothalamus and hippocampus had higher elemental concentrations than other brain regions. However, since this paper is essentially an analytical one, no attempt is made to assess these data, which are preliminary, and the possible functional role of these elements will be discussed elsewhere.

Activation Analysis↗
PubMed1983

The optimal temperature for preservation of the myocardium during global ischemia.

To determine the myocardial temperature that provides maximal preservation of the heart during global ischemic arrest, five groups of dogs were studied (6 per group). In all animals, the aorta was cross-clamped for 120 minutes. Serial biopsies were done for determination of adenosine triphosphate and creatine phosphate, and study by electron microscopy. Starling curves were derived prior to cardiopulmonary bypass and 60 minutes after bypass. Mitochondrial changes were graded on a scale of 0 to 4. In the control group (Group 1), the aorta was clamped when the rectal temperature reached 25 degrees C (myocardial temperature, 18 degrees to 22 degrees C). In Groups 2, 3, 4, and 5, myocardial temperature was maintained at 6 degrees C, 10 degrees C, 14 degrees C, and 18 degrees C (all +/- 2 degrees C), respectively, by the use of systemic and topical hypothermia and repeated injections of cold cardioplegic solution into the aortic root. All groups showed a depression of left ventricular stroke work index, particularly Group 1 (no survivors), Group 2, and Group 3. The high-energy phosphate stores were well preserved in all groups except Group 1. The mitochondrial ultrastructure showed significant changes in all groups, especially Groups 1 and 5. These data indicate that satisfactory preservation of mitochondrial ultrastructure and high-energy phosphates was achieved at myocardial temperatures lower than 18 degrees C. Extreme hypothermia (Groups 2 and 3) was associated with significant reduction in ventricular function under the experimental conditions employed.

Adenosine Triphosphate↗
PubMed1982

Relationship of brain cyclic nucleotide levels and the interaction of ethanol with chlordiazepoxide.

The effects of combined administration of ethanol (4 g/kg) and chlordiazepoxide (CDP, 12.5 mg/kg) on mouse brain c-AMP and c-GMP levels were investigated in order to test the hypothesis that the supra-additive effect of CDP on ethanol sleep time may be related to a supra-additive alteration in brain cyclic nucleotide levels induced by the combined drugs. Ethanol alone or CDP by itself did not cause any change in brain c-AMP levels, except for a transient decrease in the cerebral cortex and midbrain at 0.5 hr after ethanol injection, as well as a transient increase in the cerebellum at 0.5 hr after CDP injection. The combined drug treatment did not result in a supra-additive effect on c-AMP levels. On the other hand, c-GMP levels were depressed significantly for 4 hr after ethanol injection especially in the cerebellum. The mice regained the righting reflex when the c-GMP levels were still about 30 per cent of control values. Ethanol and CDP together induced a supra-additive decrease of c-GMP concentrations in the cerebellum at 2 and 4 hr. This resulted in a lengthened period (about 2.5 hr) during which the cerebellar c-GMP levels were below 30 per cent of control values, and this interval coincided with the increase in sleep time, suggesting a possible relationship between these two factors. Injection of ethanol and N-demethyl-chlordiazepoxide (NDCDP) simultaneously (the latter being a metabolite of CDP) also elicited a more than additive depression of cerebellar c-GMP levels at 4 hr. These data suggest that NDCDP or its metabolite could be responsible for the supra-additive effect of CDP on the ethanol-induced decrease in cerebellar c-GMP levels.

Animals↗
PubMed1982

Dissociation of tolerance and physical dependence after ethanol/chlordiazepoxide intake.

The previously-observed attenuation of withdrawal reactions in mice (group B) fed an ethanol diet containing chlordiazepoxide (CDP) was not due to a difference in the rate of disappearance of blood ethanol levels during chronic diet treatment in group B compared to mice which received only the ethanol diet (group A). Injection of group A mice with CDP or N-demethyl CDP (10 mg/kg) at the time of diet withdrawal did not result in any significant attenuation of withdrawal scores. Injection of the lactam metabolite of CDP (LCDP; 10 mg/kg) resulted in significantly attenuated withdrawal scores at 4 and 6 hr only, but the pattern of withdrawal scores were different from that for group B mice. Moreover, blood LCDP level, in mice injected with LCDP, at 4 hr was at least five times higher than that attained in group B mice (from diet containing CDP). These results support our previous conclusion that the presence of major metabolites of CDP during withdrawal could only account for a minor contribution to the protective effect. Mice in A and B did not differ in the degree of functional tolerance which developed as a result of ethanol intake. Thus, there was an apparent dissociation between tolerance and physical dependence in the mice which had consumed the CDP/ethanol diet. The magnitude of decrease of GABA levels in the cerebellum and cerebral cortex at 4 hr after withdrawal also did not differ between the two groups, suggesting the reduction in GABA levels could not be correlated with the intensity of withdrawal signs.

Alcohol Withdrawal Delirium↗
PubMed1982

Alcohol-chlordiazepoxide interaction.

The effects of chlordiazepoxide (CDP) or its N-demethyl metabolite (NDCDP) on ethanol-induced sleep time were investigated. The results indicate that CDP or NDCDP produced a supra-additive effect on the duration of sleep time induced by ethanol. These effects were not due to an alteration in the rate of elimination of blood ethanol levels. Mice which were administered CDP/ethanol had significantly higher blood and brain CDP levels than mice injected with CDP alone. The increase in CDP concentrations could be partly responsible for the supra-additive prolongation of ethanol sleep time. Our results also indicate that NDCDP and/or its metabolites were largely responsible for the supra-additive effect, because mice injected with CDP/ethanol or NDCDP/ethanol (ethanol 4 g/kg: CDP or NDCDP, 10 mg/kg) showed comparable increases in sleep time, and the blood and brain levels of NDCDP were comparable in these two groups.

Animals↗
PubMed1981

Alcohol withdrawal reactions after chronic intake of chlordiazepoxide and ethanol.

Withdrawal reactions were compared in C57BL/6J mice, which had been fed an ethanolic liquid diet containing chloridazepoxide (CDP, 3.2 or 6.4 mg/100 ml, group B or C, respectively) with those which had been administered an ethanol diet alone (group A) for 15 days. Group A showed a significantly more pronounced decrease in rectal temperature (4 to 10 hr) and a higher withdrawal score (4 to 14 hr) than mice in groups B and C. The differences in withdrawal signs still persisted even after mice were fed an ethanol diet without CDP for one extra day before withdrawal. The presence of metabolites of CDP in the blood during withdrawal could only account for a minor contribution to the protective effect. Our data are more suggestive of an increased rate of ethanol metabolism leading to lower blood alcohol levels during diet intake period as being the major factor. However we cannot rule out the alternative possibility that CDP or its metabolites might interfere with the development of tolerance to and physical dependence on alcohol.

Alcoholism↗
PubMed1980

Effect of alpha-difluoromethyl ornithine on the transplantable rat hepatoma 5123, 1-1.

Oral treatment with alpha-difluoromethyl ornithine (2.75 g/kg rat/day) simultaneous with subscapular implantation in Buffalo rats of the 5213, 1-1 hepatoma, retarded significantly the tumor growth rate for 20 days. The regimen also decreased tumor ornithine decarboxylase activity (ODC); however, the tumors growing despite treatment, maintained their malignant characteristics and ODC activity when re-transplanted into normal animals.

Animals↗
PubMed1979

Distribution of two aminotransferases and D-amino acid oxidase within the nephron of young and adult rats.

In the adult rat kidney, alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.1) and D-amino acid oxidase (EC 1.4.3.3) were measured in glomeruli, 4 parts of the proximal tubule, 2 parts of the distal tubule and in patches from the thin limb area and the papilla. These enzymes were measured in more limited parts of the nephron during postnatal development. Adult aspartate aminotransferase activities (percentage of the highest) ranged from 100 in the distal straight segment to 25 in the late part of the proximal straight segment to 10 in the thin limb and papillary area. Alanine aminotransferase (lower by a factor of 100 in absolute terms) was distributed as the mirror image of aspartate aminotransferase within proximal and distal tubules. D-Amino acid oxidase was 850-fold higher in proximal straight segments than in medullary structures. During development alanine aminotransferase increased 6-fold and D-amino acid oxidase, 4.5-fold in proximal straight tubules but aspartate aminotransferase increased in distal straight tubles 8-fold.

Aging↗