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Biomedical subjects

F S Messiha

Publications and source records attributed to F S Messiha.

At least 37 records · Page 2Linked to original sources
PubMed1991

Cerebral and peripheral neurotoxicity of chlorpromazine and ethanol interaction: implications for alcohol and aldehyde dehydrogenase.

The effects of certain experimental variables on rodents brain and liver alcohol--(ADH) and aldehyde-dehydrogenase (LALDH) were evaluated. The in vivo and in vitro effect of chlorpromazine on these enzymes was determined. Short-term housing under complete darkness differentially inhibited ADH and ALDH in distinct brain regions with ADH showing more sensitivity than ALDH. The hepatic enzymes studied were not affected by such housing conditions but a non-competitive inhibition of L-ALDH occurred as a consequence of exposure to UV lighting for 3 consecutive weeks. Short-term treatment with chlorpromazine inhibited striatal ADH which was not affected by experimentally-induced hypothermia. Likewise, both hepatic and testicular ADH were noncompetitively inhibited in vitro by chlorpromazine. The results suggest sensitivity of brain and hepatic ADH to environmental housing conditions and indicate a similarity between peripheral and cerebral ADH responses to chlorpromazine. The modulation of ADH and/or ALDH may facilitate the formation of endogenous biogenic amines derived alkaloids which have been implicated in alcohol and extrapyramidal side effects.

Alcohol Dehydrogenase↗
PubMed1991

Neurotoxicity of chlorpromazine and modulation by amantadine as a function of mouse strain.

The separate and combined effects of successive administration of amantadine, 100 mg/kg, i.p., and chlorpromazine, 0.2 mg/kg, i.p., on motor activity and whole brain levels of certain biogenic amines and major metabolites were studied in four strains of mice. These were the albino ICR, the inbred BALB/C, C57BL/6 and the hybrid CDF-I mice. Amantadine produced a strain-dependent behavioral stimulation subsequent the fourth dose. This was apparent in ICR and C57BL/6 mouse strains and was followed by a behavioral depression phase occurring during the night in C57BL/6 mice which was antagonized by chlorpromazine. Administration of chlorpromazine alone affected only CDF-1 mouse mobility. Chlorpromazine reduced only ICR mouse brain dopamine without concomitant changes in major acid metabolites. Repeated administration of amantadine prior to chlorpromazine negated this effect. Chlorpromazine enhancement of BALB/C brain serotonin and 5-hydroxyindoleacetic acid was antagonised by pretreatment with amantadine. This antagonism was also evident in BALB/C mouse brain dihydroxyphenylacetic acid. The results suggest genotypic-dependent behavioral and cerebral effects by the drugs studied. The antagonism between amantadine and chlorpromazine on brain amines may explain the therapeutic efficacy of amantadine in modulating chlorpromazine-induced extrapyramidal disorders.

Amantadine↗
PubMed1991

Beta-endorphin-like immunoreactivity: assessment of blood levels in patients with tumors of different origin.

Beta-endorphin-like immunoreactivity (beta-ELIR) blood levels in control subjects and in patients with different carcinoma and non-Hodgkin's lymphoma tumor types, were found within the same range, with the exception of one carcinoma type. This pertained to a group of patients with small cell lung cancer who had a significantly higher median beta-ELIR level compared to controls. This finding, and the fact that proopiomelanocortin expression is enhanced in tissues of this cancer type, suggest that the latter might secrete elevated beta-ELIR amounts into the blood of the affected patients.

Female↗
PubMed1991

Genetics, haloperidol and pimozide: a comparative study in two mouse strains.

Haloperidol and pimozide are the only medications approved in management of Tourette's syndrome, thought due to dopaminergic overactivity with a possible genetic trait. The effect of equal dose regimens of these drugs on some brain biogenic amines and major acidic metabolites was studied in two genetically different strains of mice. These drugs exerted strain-dependent effect on regional brain levels of the compounds measured. The results suggest a higher turnover of striatal dopamine by haloperidol than by pimozide in the albino BALB/c but not in the black C57BL/6 mouse strain which may explain the high incidences of haloperidol-induced extrapyramidal side effects. Conversely, a greater decrease in serotonin turnover by pimozide than by haloperidol was apparent in two brain regions of C57BL/6 but not in BALB/c mice which may contribute to the unwanted sedative effect reported for pimozide. The results suggest the possible contribution of genetic factors to cerebral potency of these neuroleptics which may explain variable therapeutic response and sensitivity to drug-produced toxicity in Tourette's syndrome.

Animals↗
PubMed1990

Gonadal alcohol and aldehyde dehydrogenase: in vivo and in vitro effects of psychoactive and endocrine agents.

The in vivo effect of amantadine, chlorpromazine and reserpine on testicular aldehyde dehydrogenase (T-ALDH) was studied as a function of mouse strain. The effect of Leu-enkephalin and tetrahydropapaverine on rodent T-ALDH was also studied in vivo. The in vitro effect of chlorpromazine, papaverine and scopolamine on rodent subcellular T-ALDH and testicular alcohol dehydrogenase (T-ADH) were evaluated. A strain-linked difference in endogenous T-ALDH among the three mouse strains studied was determined. Individual injection of chlorpromazine or reserpine inhibited only albino ICR T-ALDH which was alleviated by pretreatment with amantadine and, thereby, suggesting antagonism between amantadine and these agents. The Leu-enkephalin administration induced T-ALDH from saline control. Tetrahydropapaverine did not influence the enzymes studied in vivo compared to an insignificant in vitro induction of T-ADH by the O-methylated analogue papaverine. Chlorpromazine noncompetitively inhibited T-ADH in vitro. The results indicate the modulation of the enzymes studied, which are involved in both detoxification of ethanol and biogenic amine-derived aldehyde intermediates, by agents affecting the endocrine system. This suggests the potential of these testicular enzymes in the evaluation of alcohol- and drug-induced endocrine adverse reactions.

Alcohol Dehydrogenase↗
PubMed1990

Effects of amitriptyline and nortriptyline on cerebral activity of the CDF-1 mouse strain.

1. Equal dose regimens of amitriptyline, a tertiary amine tricyclic antidepressant, were more potent than nortriptyline, a secondary amine derivative, in suppressing CDF-1 mouse locomotor activity. 2. A suggestive increase in dopamine turnover rate in mouse cerebral cortex and striatal brain regions was apparent by amitriptyline but not nortriptyline. 3. A suggestive increase in serotonin turnover in mouse cerebellum and striatum was determined for nortriptyline. 4. Both antidepressants increased cerebral cortex, midbrain and cerebellum serotonin levels from saline control. 5. Increases of regional brain dopamine by amitriptyline and serotonin by nortriptyline concurrent with reuptake blockade of the respective serotonin and dopamine may contribute to their differential extrapyramidal and sedating side effects.

Amitriptyline↗
PubMed1990

Leu-enkephalin, tamoxifen and ethanol interactions: effects on motility and hepatic ethanol metabolizing enzymes.

1. Short-term treatment with tamoxifen (a nonsteroidal antiestrogen) decreased mouse spontaneous locomotor activity compared to controls. 2. Short-term pretreatment with tamoxifen prior to an acute sedative dose of ethanol potentiated ethanol-medicated behavioral depression in the mouse. 3. Injection of a small dose of Leu-enkephalin, which is devoid of effect on mouse motility, prior to an acute sedative dose of ethanol to tamoxifen pretreated female mice counteracted ethanol-produced suppression of motor activity. 4. Mouse liver aldehyde dehydrogenase was inhibited by the short-term administration of tamoxifen when given alone or preceding acute dosages of Leu-enkephalin. Concomitantly, there was an increase in blood plasma ethanol concentration from corresponding control. 5. The results of the behavioral performance test used suggest that tamoxifen possesses depressant property and exerts synergestic effect with Leu-enkephalin in antagonizing ethanol-produced behavioral depression in the mouse. 6. The enzymatic part of the study indicates an adverse metabolic influence by tamoxifen on hepatic metabolism of ethanol-derived acetaldehyde which could contribute to the potentiation of the sedative effect of ethanol.

Alcohol Dehydrogenase↗
PubMed1990

Behavioral and genetic interrelationships between locomotor activity and brain biogenic amines.

1. Spontaneous locomotor activity of four mouse strains, the albino ICR, BALB/C, the black C57 BL/6 and the brown CDF-I, was studied in conjunction with whole brain content of select biogenic amines and major metabolites. The ICR and C57BL/6 mice scored the highest and lowest motility among the strains studied, respectively. 2. The ICR mice motility were the most sensitive to experimental stress among the mouse strains evaluated. 3. Brain dopamine concentrations were greater in ICR and CDF-I mice than the other two mouse strains. This is compared to high serotonin and 5-hydroxyindole acetic acid levels determined in C57BL/6. 4. A relationship between the ICR mouse strain with a high motility and the ratios of brain dopamine:homovanillic acid and between serotonin:5-hydroxyindole acetic acid was established. 5. An inverse relationship between ICR mice motility and the ratio of metanephrine and normetanephrine:3-methoxy-4-hydroxyphenylglycol (MHPG) was determined. 6. It is concluded that genetic predisposition may account for a relationship between motor activity and brain biogenic amines which may give insight into the susceptibility of different patients to the development of certain extrapyramidal diseases.

Animals↗
PubMed1990

Effect of almond and anis oils on mouse liver alcohol dehydrogenase, aldehyde dehydrogenase and heart lactate dehydrogenase isoenzymes.

The effects of short-term intraperitoneal injection of diluted almond or anis oil on heart lactate dehydrogenase isoenzymes, liver alcohol dehydrogenase and subcellular aldehyde dehydrogenase were studied in the female mouse. Hepatic alcohol dehydrogenase was induced from control by administration of almond oil 3.2 g/kg/d for 7 days, or anis oil 1.6 g/kg/d for 7 days. Treatment with almond but not anis oil inhibited both cytoplasmic and mitochondrial liver aldehyde dehydrogenase. The mitochondrial isoenzyme with an apparently low Km was also inhibited by the almond oil trial. No significant changes occurred in heart lactate dehydrogenase isoenzymes by the treatments used. The enzymatic inhibition kinetics were found to be non-competitive. The apparent Km for almond-treated mouse aldehyde dehydrogenase was greater than the controls. This indicates lower substrate affinity for almond oil than for acetaldehyde. The results suggest adverse hepatic metabolic interaction between almond oil and alcohol.

Alcohol Dehydrogenase↗
PubMed1990

Behavioral genetic analysis of regional mouse brain biogenic amines, acidic metabolites and motor activity.

1. Comparative analyses of regional brain biogenic amines and spontaneous locomotor activity of three mouse strains suggest a genotype dependent relationship. 2. A positive correlation between striatal dopamine and locomotor activity was determined in the inbred albino BALB/c mouse strain. 3. An inverse relationship between some brain regions serotonin and motility was found in the inbred black C57BL/6 mouse strain. 4. No correlation could be established between brain monoamines and motor activity in the hybrid CDF-1 mouse strain. 5. The results suggest that inbred BALB/c and C57BL/6 mouse strains may be useful animal models for studying dopaminergic and serotonergic acting agents, respectively.

Animals↗
PubMed1990

Differential modulation of mouse brain biogenic amines by haloperidol and pimozide: implications in Tourette's syndrome.

1. A comparison between the effect of equal dose regimens of Tourette's medications on mouse motor activity and regional brain monoamines suggests differential responses which may underlie drug-induced side-effects. 2. Haloperidol was more potent than pimozide in altering striatal dopamine concentration which may account for the greater incidence of haloperidol-induced extrapyramidal disorders compared to pimozide. 3. Pimozide, but not the haloperidol treatment, altered brain serotonin concentrations to suggest a decrease in turnover rate which may underlie pimozide-caused sedation in Tourette's syndrome. 4. Pimozide was more potent than haloperidol in duration of behavioral depression which suggests differential dopamine receptor subtypes blockade. 5. Pimozide was more potent than haloperidol in altering 3 of the 6 brain regions content of norepinephrine-derived normetanephrine which may be responsible for the increase in blood pressure reported during pimozide treatment.

Animals↗
PubMed1990

Effect of methionine on regional CDF-1 mouse brain monoamines.

The effect of methionine on cerebral content of dopamine, serotonin and major acidic metabolites was studied in distinct CDF-1 mouse brain regions. Methionine was administered 30 mg/kg for five trials over 24 h and mice were sacrificed 30 min post the terminal treatment. Methionine exerted differential effects on regional brain concentrations of 3,4-dihydroxyphenylacetic acid and serotonin. The results suggest methionine-mediated decreases of dopamine turnover in the hippocampus and medulla compared to increases of serotonin turnover in the cerebral cortex and midbrain regions. The results indicate a central action for methionine as related to endogenous neurotransmitters measured which may precede the abnormal O- or N-dimethylation ascribed to methionine and the insuing adverse effects postulated in schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Cholinergic, anticholinergic agents and ethanol interaction.

The effect of cholinergics and an anticholinergic agent on hepatic ethanol metabolizing enzymes was studied. Short-term administration of the cholinomimetic arecoline or the anticholinergic scopolamine induced rat liver mitochondrial aldehyde dehydrogenase (L-ALDH) isoenzyme with the apparent high and low Km, respectively. In addition, scopolamine inhibited cytoplasmic L-ALDH. This suggests differential sensitivity of the L-ALDH isoenzymes to these agents. Scopolamine and the cholinomimetic pilocarpine enhanced rat and mouse liver alcohol dehydrogenase (L-ADH) in vitro, respectively. This indicates species-dependent effect of these agents on L-ADH. The results suggest interaction of the cholinergic system with ethanol metabolizing enzymes which may contribute to the peripheral action of alcohol.

Aldehyde Dehydrogenase↗
PubMed1990

Papaverine, tetrahydropapaverine and ethanol metabolizing enzymes.

The effects of tetrahydropapaverine (THP) and papaverine (PAP), an O-methylated analogue, on rat liver alcohol dehydrogenase (L-ADH) and aldehyde-dehydrogenase (L-ALDH) were studied in vitro. The action of THP on these enzymes was also evaluated in vivo in conjunction with its effect on voluntary intake of ethanol by the rat. Both L-ADH and mitochondrial L-ALDH were inhibited in vitro in the presence of 10(-4) M THP. Conversely, stimulation of L-ADH and L-ALDH occurred by PAP in the concentration range between 10(-4) to 10(-6) M in vitro. Acute or daily administration of THP for five consecutive days did not alter voluntary intake of ET by the rat or changed specific activity of these hepatic enzymes in vivo. The structure activity of these compounds in relationship to the enzymes studied suggest the importance of O-methylation on the enzymatic effect studied which may possibly underlie some of the hypothesized action of THP on libation of alcohol.

Alcohol Dehydrogenase↗
PubMed1990

Gossypol modulation of mouse heart and liver lactate dehydrogenase isoenzymes as a function of gender.

Acute treatment with gossypol produced both tissue specific and sex-dependent alterations of M and H subunits of mouse lactate dehydrogenase. Gossypol induced female mouse heart cytoplasma H subunit and inhibited both enzyme subunits in the male mouse. Gossypol induced mouse liver mitochondrial lactate dehydrogenase subunit M in both sexes 50 hrs after acute drug administration while was ineffective on the testicular enzyme. Induction of hepatic lactate dehydrogenase may enhance NADH:NAD ratio, resulting in alteration of cellular redox status and reduction of NAD utilization by other dehydrogenases. The gossypol-mediated sex-dependent changes of heart lactate dehydrogenase isoenzymes may be of value in the prediction of certain aspects of gossypol toxicity.

Animals↗
PubMed1989

Beta-endorphin in the brainstem and the cerebellum of the human infant: regional levels' profile assessed with immunoaffinity chromatography and solid phase radioimmunoassay.

The regional levels' profile of human beta-endorphin (beta h-EP) was studied in the brainstem and the cerebellum of 16 infant victims of "Sudden Infant Death Syndrome" and other death causes. An immunoaffinity chromatography procedure based on a monoclonal antibody directed specifically against the N-terminus of beta-EP was used to extract this peptide from the tissue samples. Beta-EP was then assessed quantitatively by means of a very sensitive solid phase radioimmunoassay (using a polyclonal antibody specific for the C-terminus of beta-EP) developed especially for the study presented here.

Brain Stem↗
PubMed1989

Cerebral beta-endorphin levels in a woman with Prader-Labhart-Willi syndrome.

By means of a specific two-site immunoradiometric assay, we explored the beta-endorphin levels in various brain regions of a patient affected by Prader-Labhart-Willi Syndrome. The rank of the beta-endorphin levels of five cerebral zones (hypothalamus, substantia grisea centralis, pons dorsalis, medulla oblongata dorsalis medialis, thalamus medialis) of the patient was homologous to that of subjects without the syndrome, except for the medulla oblongata dorsalis medialis. In patient with the Prader-Labhart-Willi Syndrome this region had a higher ranking level than in subjects without it. However, a functional meaning cannot be attributed to such difference because the patient of this study did not exhibit neurological disturbances relating to elevated beta-endorphin levels in the medullary region investigated.

Adult↗