Interaction of glycine with ethanol.
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Animals↗
Biomedical subjects
A W Chan
Publications and source records attributed to A W Chan.
Combined metabolic effects of ethanol and thiamine deficiency in the central nervous system.
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Adenosine Triphosphate↗
Localization of glutamine accumulation and tubular reabsorption in rat nephron.
Glutamine accumulation in rat kidney was investigated by giving large loads of gluta, mate and aspartate and measuring glutamine changes in seven completely defined portions of the nephron and in small patches from the thin limb area and from the papilla. Both glutamate and aspartate (which is partly coverted to glutamate) caused increases up to sixfold in glutamine which were mainly confined to the proximal straight tubule. Plasma glutamine is minimally affected. In contrast, large glutamine loads doubled plasma glutamine and caused about a doubling of glutamine concentrations in all parts of the nephron, but resulted in no greater change in the proximal straight tubule than elsewhere. Simultaneous inulin and glutamine measurements make it seem likely that the proximal convoluted tubule is a major site of glutamine reabsorption. The low glutamine concentrations in these cells (only 40% higher than that in plasma) indicate a very small gradient at the antiluminal surface. We suggest that the proximal straight tubule is the major site of glutamine synthesis but that it may not be an important site of glutamine breakdown.
Animals↗
Differential effects of pentobarbital and ethanol in mice.
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Animals↗
Gamma Aminobutyric acid in different strains of mice. Effect of ethanol.
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Aminobutyrates↗
Effect of methionine sulfoximine on glutathione and amino acid levels in the nephron.
The effect of L-methionine-DL-sulfoximine (MSO) on renal glutathione concentration and aspartic acid transport has been studied by analyses of parts of individual freeze-dried glomeruli, early and late proximal convoluted, early and late proximal straight, and distal straight and convoluted tubules, and patches from thinlimb and papilla areas. Glutathione normally varies threefold along the kidney nephron, being highest in the convoluted and early straight proximal tubule, lowest in the distal straight tubule. Large loads of aspartate cause 20% diminution of glutathione in outer cortex, due entirely to changes in proximal tubule segments. MSO alone lowers glutathione 90% in all parts of the proximal tubule, with no change elsewhere. MSO does not affect the large increase in aspartate in proximal tubules caused by saturating aspartate loads, suggesting that glutathione is not directly involved in transport of this amino acid. Aspartate loads cause a large increase in renal glutamine, which is especially marked in the proximal straight tubule. MSO effectively blocks this increase and depresses tissue glutamine below normal levels.
Amino Acids, Dicarboxylic↗
Direct quantitation of amino acid transport and metabolism in segments of individual nephrons.
A new approach to amino acid transport in kidney is described which may be useful for study of renal transport in general. The amino acid is given in threshold and above threshold loads along with inulin as a glomerular filtrate marker. The kidney is quickly frozen at --60 degrees. Frozen 16 mum sections are dried at --40 degrees, and identified parts of single nephrons are analyzed for amino acid given, certain metabolites and inulin. The relationship of amino acid to inulin along the tubule is used to indicate changes relative to the glomerular filtrate. With either aspartate or glutamate loads, both amino acids accumulate to high levels in segments in which transport is believed to take place (proximal convoluted and straight tubules). Glutamine also accumulates to a high degree, but only in the proximal straight tubule.
Amino Acids↗
Resistance to Levamisole (R12456) in heat-stable alkaline phosphatases.
The inhibitory effect of Levamisole (R12456) on human alkaline phosphatases has been studied. At a concentration of 0.1 mM it is possible to differentiate the source of the enzyme. Enzyme activity relatively resistant to Levamisole (less than 20 percent loss) is present in serum with the Regan isoenzyme, in placental extracts, in the intestinal "B" preparation and in heat-stable alkaline phosphatases "unmasked" after treatment at high ionic strength.
Alkaline Phosphatase↗
A quantitative histochemical approach to renal transport. I. Aspartate and glutamate.
Renal transport was studied by direct analysis of specific segments of the nephron for the substance transported. Rats were given inulin plus loads of glutamate or aspartate. Glomeruli, six different identified segments, and patches from thin-limb and papillary areas were dissected from individual nephrons in freeze-dried sections. Large amounts of the amino acid (up to 35 mmol/kg) accumulated in segments in which transport is believed to occur. With subthreshold loads, large amino acid increments were confined to earlier proximal segments. With loads above threshold, increases occurred throughout the proximal tubule. The early convoluted tubule probably has less transport activity than the rest of the proximal tubule. Both dicarboxylic amino acids accumulate in large amount when one is given. Aspartate is probably formed within the tubule after a glutamate load. This new histochemical approach may have general applicability for more precise localization of transport cells, for assessing changes in those cells during transport, and for study of structures inaccessible to micropuncture.
Amino Acids↗
The structural and aggregation properties of the synthetic C-terminal half (104-mer) polypeptide from HIV p24gag resemble those of full-length protein.
The aggregation and structural properties of the synthetic C-terminal half [Ala330, Ala350(270-373; 104-mer)] polypeptide from HIV-1 p24gag were studied. In concentrated solutions the synthetic polypeptide aggregated to tetramers which, upon dilution, gave a mixture of monomeric and dimeric and dimeric species. These results correlated well with the in vitro aggregation properties of recombinant p24. The tetrameric form of the synthetic polypeptide had a pI which differed by about four units from that of the mixture of monomeric and dimeric species. CD studies indicated that the latter contained, in aqueous solutions, a compact molecule lacking, however, a defined tertiary structure. Addition of MeOH to aqueous solutions of both tetramer and monomer/dimer mixture induced a more defined structure, which was assigned to that of an alpha + beta protein in agreement with secondary structure predictions. A model of the dimeric form of the 104-mer, which takes into account the results presented here and those from a study on the specificity of a set of anti-104-mer MoAbs, is presented. Finally, the results indicated that the structure of the 104-mer in its dimeric form is similar to that adopted by the same sequence when part of full-length p24.
Amino Acid Sequence↗
Cross-tolerance between ethanol and chlordiazepoxide.
Drug-induced hypothermia was used to investigate drug tolerance and cross-tolerance. C57BL/6J mice, which were injected with a single dose of chlordiazepoxide (CDP; 30 mg/kg) one day before and reinjected with an equivalent dose of CDP the next day, did not develop tolerance to the drug. However, ethanol-pretreated (3.5 g/kg, 24 hr earlier) mice, when injected with CDP (30 mg/kg), showed cross-tolerance to CDP. The cross-tolerance was short-lived (less than 48 hr). On the other hand, CDP-pretreated mice (30 mg/kg, 24 hr earlier) did not show cross-tolerance to ethanol. The lack of a reciprocating effect of CDP-pretreatment was not likely to be due to the difference in initial dosage between ethanol and CDP. It may be due to different rates of tolerance development or different mechanisms of actions between CDP and ethanol. Mice chronically treated with ethanol also showed a similar degree of cross-tolerance to CDP compared to those exposed to an acute dose of ethanol.
Animals↗
Substitution of chlordiazepoxide for ethanol in alcohol-dependent mice.
Alcohol dependence was induced in C57BL/6J mice by administration of a liquid diet containing ethanol. These mice showed alcohol withdrawal signs when the alcohol diet was withdrawn. However, when the alcohol diet was substituted with three liquid diets containing different amounts of chlordiazepoxide (CDP; 0.4, 1 and 2 mg/ml), the alcohol withdrawal signs were fully suppressed by CDP. The CDP diet administration was continued for 14-24 days. At termination of the diet treatment, the mice showed CDP withdrawal signs. Similar signs, but much more short-lived, can be precipitated by injection of the benzodiazepine receptor antagonist, RO-15-1788. The results are consistent with the hypothesis that alcohol-dependent mice are cross-dependent on CDP. This report constitutes the first experimental demonstration of cross-dependence between ethanol and CDP. The reverse phenomenon, namely, CDP-dependent mice being cross-dependent on ethanol, remains to be investigated.
Animals↗
Identification of alcoholism in young adults by blood chemistries.
A stepwise linear discriminant analysis was conducted between young adult alcoholics in an alcoholism treatment center and non-alcoholic college students. Analysis of 31 commonly ordered clinical laboratory tests yielded three significant variables (urea nitrogen, potassium and MCV) which correctly classify 89% of alcoholics and 92% of non-alcoholics.
Adolescent↗
Muscle fiber composition and length-tension relationships in rats chronically exposed to alcohol.
Adult Fischer 344 rats were fed an alcohol diet (7-9 g/kg/day) for 12 weeks and were compared to pair-fed controls with regard to the contraction and fiber characteristics of the gastrocnemius and plantaris muscles of the leg. Muscles were isolated in situ with blood and nerve supplies intact. The muscles were stretched by 1 mm increments and were stimulated at each muscle length with a voltage (1 msec pulse) that had been observed to produce maximal twitch force at the initial muscle length. Maximal twitch tension was found to be only 10% less in alcohol than pair-fed rats and the increase in force resulting from stretching was approximately 15% less in alcohol than pair-fed rats. No significant changes in sciatic nerve conduction velocities were produced by alcohol exposure. Moreover, no significant differences in muscle weight or the number and size of Type I, Type IIa or Type IIb muscle fibers were observed. Although the 12 weeks of alcohol exposure affected muscle physiology and histology in the direction of increased impairment, the differences were not large enough to be statistically significant.
Alcoholism↗
Absence of acute tolerance to ethanol hypnosis in F-344 and BN/BIRIJ rats.
Male Fischer 344 (F-344) rats of three different ages (4, 13, and 25 months) and male Brown Norway (BN/BIRIJ) rats (4 months) were injected (IP) with a hypnotic dose of ethanol (3.0 g/kg, 10% w/v in saline). Half of the animals were decapitated and brains extracted immediately upon loss of the righting reflex (LRR), while the other half were allowed to reach recovery of the righting reflex (RRR), at which time brains were extracted. Brain alcohol analyses revealed significantly higher concentrations in young F-344 rats at both LRR and RRR, indicating less sensitivity of target tissue to ethanol hypnosis in the young of that strain. All age groups of the F-344 rats as well as the young BN/BIRIJ rats displayed lower brain concentrations of ethanol at RRR than at LRR, a finding opposite to that characteristic of acute tolerance. The relationship of LRR to RRR values did not differ among the age groups of F-344 rats. We conclude that the F-344 and BN/BIRIJ strains do not develop acute tolerance to ethanol hypnosis. The findings are consistent with the hypothesis that animals with low ethanol preferences, such as the F-344 and BN/BIRIJ strains, also have low capabilities to develop acute tolerance to ethanol hypnosis.
Aging↗
Factors affecting the discriminant function analysis of blood chemistry profiles.
The discriminant function analysis (DFA) of a battery of blood chemistry tests is generally more sensitive and specific than single biochemical test in detecting alcoholism or hazardous drinking. This study examined factors affecting the DFA of blood chemistry profiles (BCP) from alcoholics (ALC) in treatment, primary care outpatients (PC), and the general population (GP). Our data indicate that of the 32 variables in the BCP, 14 are not correlated with alcohol intake or consequences and can be deleted from the set considered for use in the DFA. Confounding medical conditions in the data set used in the DFA did not adversely affect the correct classification of ALC or heavy drinkers. It was not necessary to use only extreme groups (e.g., alcoholics vs. light drinkers/abstainers) to develop the discriminant function. Transformation of some blood variables greatly improved the selection of key variables in the DFA. Another finding was that there was little benefit from fitting the DFA to the demographics of subjects. When the BCP was combined with the results of a brief questionnaire, the TWEAK, it only improved slightly the classification power of the DFA based only on the TWEAK questions.
Adolescent↗
A prospective study of painful symptoms, small-fibre function and peripheral vascular disease in chronic painful diabetic neuropathy.
Fifty diabetic patients with chronic painful sensorimotor neuropathy were studied prospectively to clarify the natural history of this condition and the roles of small-fibre damage and concomitant peripheral vascular disease (PVD). Initially, 30 patients had no significant PVD (ankle:brachial Doppler ratio > 1.0). Pain was assessed using a visual analogue scale (0-10 cm), and small-fibre function by thermal limen (TL), heat-pain threshold (HPT), and weighted pinprick threshold (PPT). At follow-up, on average 3.6 years later (range 3.0-4.1), 11 patients had died (6 with PVD) and contact had been lost with 6. Pain scores fell in subjects without PVD (n = 24; median (range), from 4.8 (0.5-10.0) to 2.0 (0.0-9.2) cm, p < 0.001) and also in those with PVD (n = 9; from 5.1 (2.0-8.2) to 2.1 (0.0-8.0) cm, p < 0.05). Seven patients (5 without PVD) became painfree; at presentation, these 7 patients had experienced pain for a shorter period of time. Despite this symptomatic improvement, small-fibre function generally deteriorated in both groups, with significant worsening (p < 0.05) of HPT and PPT in patients without PVD, and in HPT and TL in patients with PVD. Neuropathic pain therefore tends to improve with time and can resolve completely. By contrast, small-fibre function continues to deteriorate, indicating that these peripheral measures do not predict the evolution of painful symptoms. The presence or absence of PVD does not appear to affect the natural history of neuropathic pain or its symptomatology.
Adult↗
Alcoholism and epilepsy.
There is a scarcity of population-based epidemiological investigations concerning the prevalence of epilepsy among alcoholics, and of alcoholism among epileptic patients. Available data seem to suggest that the prevalence of epilepsy among alcoholics is at least triple that in the general population, and that alcoholism may be more prevalent among epileptic patients than in the general population. The term "alcoholic epilepsy" has been used with varying definitions in different investigations. It is suggested that a uniform definition be adopted so as to minimize confusion when comparing data from different laboratories. Although there is general agreement that excessive alcohol intake can increase the frequency of seizures in epileptic patients, limited available data suggest that light to moderate social alcohol drinking may not affect seizure frequency. However, epileptic patients should be warned about the possible adverse effects of alcohol, especially those who have refractory forms of epilepsy. Except for a few anomalous cases, evidence for the direct seizure-provoking effect of alcohol is not strong. This is because it is difficult to pinpoint alcohol as the only etiology; more likely, alcohol is only one factor among others (e.g., head trauma, cerebral infarct, alcohol withdrawal, and metabolic effects of alcohol) in provoking seizures. Because seizures are a symptom and not a disease, it is often difficult to distinguish epileptic seizures from alcohol-withdrawal seizures. Patients with only the latter kind of seizures should not need chronic antiepileptic medication.
Alcoholism↗