Differential tolerance to the intestinal inhibitory effect of opiates in mice.

The occurrence of unidirectional noncross-tolerance to heroin and etorphine induced antinociception in morphine tolerant mice prompted this study to determine whether this phenomenon occurs for opiate induced inhibition of intestinal transit. Tolerance to the intestinal inhibitory effect (charcoal meal test) of s.c.

Metabolism of malondialdehyde by rat liver aldehyde dehydrogenase.

Mammalian liver contains a group of pyridine nucleotide linked aldehyde dehydrogenases [E.C. 1.

Drug metabolism in isolated proximal tubule cells: aldehyde dehydrogenase.

The mammalian kidney is composed of numerous cell populations associated with the interstitial spaces, vasculature and various portions of the nephron. Not surprisingly, mammalian kidneys also exhibit an array of drug metabolizing activities, including the pyridine nucleotide-linked aldehyde dehydrogenase(s) (ALDH). To define the ALDH activity in segment 2 of the proximal tubule, a portion of the nephron which frequently shows drug-induced pathology, proximal tubules were isolated by purely mechanical methods from female rabbits.

Time course of the carbon tetrachloride-induced decrease in mitochondrial aldehyde dehydrogenase activity.

Hepatic microsomal enzymes like cytochrome P-450 and glucose 6-phosphatase are inhibited after exposure to CCl4 in vivo. Since comparatively less is known about the effects of CCl4 on nonmicrosomal enzymes, we investigated the rapidity by which CCl4 inhibits the low Km mitochondrial aldehyde dehydrogenase (ALDH) isozyme, an enzyme known to be inhibited 24 hr after CCl4 treatment. The activity of this ALDH isozyme was significantly lowered 6 and 12 hr after a single 1 ml/kg intragastric dose of CCl4.

Hepatic aldehyde dehydrogenases and lipid peroxidation.

Recent findings have shown that microsomal membrane lipid peroxidation generates a variety of reactive aldehydic products. The interaction of lipid peroxidation products with hepatic aldehyde dehydrogenases (ALDH) was studied using rat liver subcellular fractions. The well-documented membrane peroxidation product malondialdehyde (MDA) was studied to determine if ALDH isozymes play a role in metabolism of this aldehyde.

Pharmacogenetic approaches to the neuropharmacology of ethanol.

The literature cited in this review clearly demonstrates that many of the behavioral and pharmacological responses to either acute or chronic actions of alcohol are indeed heritable. This conclusion is supported by data derived from several different animal models that have been genetically manipulated to display a wide variety of alcohol-related responses. It is doubtful if any one specific animal model will be developed that will serve as a prototype for human alcoholism.

Selective breeding for a multivariate index of ethanol dependence in mice: results from the first five generations.

Starting with a population of genetically heterogeneous mice (HS/lbg), selection for a multivariate index of the ethanol withdrawal syndrome has been initiated. The study uses within-litter selection to minimize inbreeding and includes replicate high, low, and control lines. After five generations, results indicate that selection is proceeding successfully.

Subcellular distribution and kinetic parameters of HS mouse liver aldehyde dehydrogenase.

1. Aldehyde dehydrogenase subcellular distribution studies were performed in a heterogeneous stock (HS) of male and female mice (Mus musculus) with propionaldehyde (5 mM and 50 microM) and formaldehyde (1 mM) and NAD+ or NADP+. 2.

Inhibition of mitochondrial aldehyde dehydrogenase by malondialdehyde.

Rat liver mitochondria contain an aldehyde dehydrogenase (ALDH, EC 1.2.1.

[Neuroradiology, clinical picture and pathology of cerebral venous angiomas].

Twelve cases of venous angioma of the brain are presented. The neuroradiological and clinical findings in our series as well as in 45 previously reported cases are summarized. Angiography shows a normal arterial phase but consecutively a network or medusa-like pattern of numerous dilated medullary veins.

Analyses of nicotine and cotinine in tissues by capillary gas chromatography and gas chromatography-mass spectrometry.

Selective extraction and chromatographic techniques have been developed to measure low nanogram quantities of nicotine and cotinine in tissues. Analyses were performed by capillary column gas chromatography with a specific nitrogen-phosphorus detector and by gas chromatography-mass spectrometry. With close structural analogues for internal standards, high quantitative accuracy and precision were demonstrated for the range 5-1000 ng per g of tissue.

Ethanol elimination rates in mice: effects of gender, nutrition, and chronic ethanol treatment.

Twenty male and 20 female mice of a heterogeneous stock were assigned to each of three groups. One groups was administered ethanol in a liquid diet for 9 days, a second group was fed an isocalorically controlled diet containing no ethanol for the same length of time, and the third group was fed standard lab chow. Each animal was injected with a dose of ethanol equal to 3.

Increase in hepatic microsomal ethanol oxidation by a single dose of ethanol.

A single injection of ethanol was shown to produce a relatively rapid increase in the in vitro activity of aniline hydroxylase and in microsomal ethanol oxidation. Stimulation of the microsomal ethanol oxidating system (MEOS) was dependent on the ethanol dose and time after dosing. Hepatic MEOS activities were significantly increased 2, 3 and 4 hr after a single 4.

An overview of the genetics of psychopathology.

The suggestion that psychopathologies are in part mediated by aberrant catecholamine metabolism has resulted in one of the more rapidly growing areas of pharmacogenetics. Collectively, the studies conducted to date indicate that psychopathological conditions have multiple causes which cannot be related to single genetic or biochemical deficits. However, through multidisciplinary research integrating behavioral, genetic, and biochemical approaches, a great deal of insight may be gained concerning the causes of psychopathological disorders and the use of drug therapy to modify the course of these illnesses.

Studies on carbon tetrachloride-ethanol interactions in mice.

Male C57BL/6J (C57) and DBA/2J (DBA) inbred mice were dosed with either corn oil or carbon tetrachloride (CCl4) in corn oil 24 h before a 3.25 g/kg i.p.

Selective breeding in mice for severity of the ethanol withdrawal syndrome.

Starting with a foundation population of 200 genetically heterogeneous mice (HS/Ibg), selective breeding has been initiated for a multivariate index of the ethanol withdrawal syndrome. This paper discusses the advantages of using multivariate indices to define pharmacological concepts. The seven variables included in our multivariate index are described.

Metabolic interactions of aldehyde dehydrogenase with therapeutic and toxic agents.

The specific physiological roles of ALDH have not been determined. In this overview, we have identified malondialdehyde as one potential endogenous toxic aldehyde that is oxidized by ALDH. Undoubtedly, there are other cytotoxic aldehydes which occur in several different tissues that are detoxified by this same system of enzymes.

Inhibition of rat liver aldehyde dehydrogenase by carbon tetrachloride.

Current data suggests that aldehydic products of lipid peroxidation possess substantial cytotoxic properties. Carbon tetrachloride (CCl4), a potent stimulator of hepatic lipid peroxidation, was tested for possible effects on hepatocellular aldehyde metabolism. CCl4 (1 ml/kg) produced an elevation in serum alanine aminotransferase activity, hepatic fatty infiltration, centrilobular necrosis and significant decreases in the content of hepatic microsomal cytochrome P-450.