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Biomedical subjects

G Nahas

Publications and source records attributed to G Nahas.

At least 19 recordsLinked to original sources
PubMed1992

The human toxicity of marijuana.

The pathophysiological effects of marijuana smoke and its constituent cannabinoids were reported first from in-vitro and in-vivo experimental studies. Marijuana smoke is mutagenic in the Ames test and in tissue culture and cannabinoids inhibit biosynthesis of macromolecules. In animals, marijuana or delta 9-tetrahydrocannabinol (THC), the intoxicating material it contains, produces symptoms of neurobehavioural toxicity, disrupts all phases of gonadal or reproductive function, and is fetotoxic. Smoking marijuana can lead to symptoms of airway obstruction as well as squamous metaplasia. Clinical manifestations of pathophysiology due to marijuana smoking are now being reported. These include: long-term impairment of memory in adolescents; prolonged impairment of psychomotor performance; a sixfold increase in the incidence of schizophrenia; cancer of mouth, jaw, tongue and lung in 19-30 year olds; fetotoxicity; and non-lymphoblastic leukemia in children of marijuana-smoking mothers.

Accidents, Traffic↗
PubMed1992

Inhibition by cocaine of the baroreflex in the rat.

Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg/kg of cocaine or an equal volume of saline. Five minutes later, stimulation of the baroreflex was performed by bilateral clamping of the two carotids for a period of 2 min. The same maneuver was repeated at 12, 24, and 31 min. Analysis of variance for repeated measures indicated that before carotid artery clamping, there was no significant difference between blood pressure measurements of the saline- and cocaine-treated groups. A two-factor analysis of variance of the repeated measures of the maximal variation in systolic pressure after each clamping showed a significant difference between control and cocaine-administered groups (P < 0.001), with the former displaying a much greater increment in blood pressure after carotid clamping. Cocaine exerts an inhibitory effect on the baroreflex that may be mediated through the increased angiotension II caused by the alkaloid.

Animals↗
PubMed1992

[Potentiation of the acute toxic effects of cocaine by ethyl alcohol].

Ethyl alcohol increases significantly the lethality of cocaine intoxication in the rat. This lethality is not modified by nicardipine or flunarizine, antidotes to cocaine, and might be due to the formation of a newly identified active metabolite cocaethylene. In addition alcohol like cocaine inhibits the baro receptor reflex.

Animals↗
PubMed1989

[Cocaine and disturbances of adrenergic neurotransmission].

Cocaine releases peripheral and central stores of catecholamines and their plasma concentration increases in very significantly under the influence of the drug. One also observes a vaso-constriction of cerebral and coronary arteries. Decreases in blood flow through those vessels have been observed in cocaine addicts examined with the magnetic resonance and positron emission tomography techniques. Some of these changes may still be present 15 days after withdrawal. The authors suggest an hypothesis to account for the general mode of action of cocaine. The synaptic increase in catechol produced by this drug is calcium dependent and would induce an "up regulation" of receptor proteins of calcium channels with increased calcium intracellular fluxes. There would be an increase in catecholamine neuronal turnover and synthesis not a depletion. Conversely the adrenergic post-synaptic receptors would undergo a "down regulation". Such impairment of adrenergic neurotransmission is associated with an increase in Angiotensin II release and a decreased GABA activity. Sensory stimuli resulting from this impairment induce a dominant memory associated with drug seeking and consuming behavior.

Adrenergic Fibers↗
PubMed1988

[A technic for selection of antidotes to an acute lethal poisoning].

The dose of a toxic substance which is lethal to the rat within 15 min (LD100.15 min) and its specific antidotes are defined. Atropine, diazepam and nimodipine in sequential administration are effective antidotes to a LD100.15 min (1.5 mg/kg) of paraoxon, an anticholinesterase.

Animals↗
PubMed1987

Comparative effects of intravenously administered alizapride and prochlorperazine in cisplatin-induced emesis.

A randomized, double blind crossover trial compared the antiemetic effects of alizapride, a benzamide, and prochlorperazine, a phenothiazine, both administered intravenously to 32 patients treated with chemotherapy combinations containing cisplatin. The total dose of alizapride administered to each patient was 14 mg/kg, and of prochlorperazine .56 mg/kg, divided in five doses. Although alizapride resulted in complete protection against emesis in 31% of the patients during their first course of cisplatin therapy, 42% of those who received alizapride had five or more episodes of emesis. Although prochlorperazine was less effective in offering complete protection against emesis, only 15% of the patients receiving this drug vomited more than five times. The duration of emesis during prochlorperazine treatment was also significantly shorter than during alizapride therapy (p less than 0.02). Optimal dosage and pharmacokinetic distribution of both drugs should be investigated further.

Adult↗
PubMed1987

Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.

Flunarizine and nimodipine, Ca2+ modulators which exert antagonist effects against catecholamines and serotonin and have specific action on the brain, were used as antidotes to imipramine toxicity in the rat. Imipramine, a tricyclic antidepressant, inhibits synaptic reuptake of catecholamines and serotonin. Flunarizine administered concurrently with imipramine increased survival time significantly (p less than 0.04). After a lethal dose of imipramine (85 mg/kg) 5 out of 5 animals treated with flunarizine (2.37 +/- 1.21 mg/kg in divided doses) and 4 out of 5 animals treated with nimodipine (0.36 +/- 0.11 mg/kg) survived. The acute toxicity of imipramine might be related, in part, to drug-induced alteration in turnover of excitatory neurotransmitters which will induce intracellular Ca2+ accumulation and damage to vital organs. These toxic effects of endogenously produced neuroamines may be antagonized by nimodipine or flunarizine.

Animals↗
PubMed1986

Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine.

Nitrendipine, a Ca2+ modulator was tested in the rat as an antagonist to the cardiac toxicity of cocaine and as an antidote to the acute lethal effects of this drug. In a first series of experiments, nitrendipine (1.46 X 10(-3) mg/kg/min) when simultaneously administered intraarterially with cocaine (2 mg/kg/min) suppresses the arrhythmias induced by cocaine and increases survival time from 73 +/- 33 min to 309 +/- 118 min and the lethal dose of cocaine from 146 +/- 66 mg/kg to 618 +/- 236 mg/kg (p less than 0.003). Nitrendipine also protects the heart from the acute morphological lesions induced by cocaine administration and antagonizes some of the central effects of cocaine. In a second series, 5 rats administered 60 mg/kg of cocaine intraperitoneally had a survival time of 8'06 +/- 5'20. Death was attributed to convulsions and respiratory arrest. Animals treated with nitrendipine (129 +/- 23 mg/kg) 4'30" after cocaine administration survived. Nitrendipine appears to have general protective effects against cocaine cardiac toxicity and the acute lethal effects of this alkaloid.

Animals↗
PubMed1985

Cardiac dynamics of the Langendorff perfused heart.

The Langendorff perfused heart is studied in a closed system with (i) automatic regulations to maintain constancy of the perfusion column (Krebs-Henseleit + 0.5% albumin or 25-30% washed erythrocyte suspension), (ii) continuous recording of rate, coronary flow, and supravalvular aortic pressure. A microcomputer with software interface is used for storage treatment and on-line analysis of the recorded variables. In 38 preparations perfused with Krebs-Henseleit, minimal diastolic (61.2 +/- 2.8 mm Hg) is significantly below and peak systolic (98.7 +/- 3.6 mm Hg) significantly above perfusion pressure (80 mm Hg). Pressure difference between minimal diastolic and peak systolic (delta P) is 37.5 +/- 1.8 mm Hg. Increases in perfusion pressure will be associated with increases of coronary flow and delta P, which is also increased by isoprenaline administration. Oxygen consumption decreased by 76% when perfusion pressure was lowered from 80 to 60 mm Hg in hearts perfused with a 30% erythrocyte suspension. All of these experimental results were interpreted as indicating that delta P measured in this system resulted from an ejected volume (x acceleration) from the heart. The ejected volume corresponds to a valvular leak caused by the rigid nature of the system which is devoid of aortic compliance. delta P may be considered an index of left ventricular performance, an indication that the Langendorff preparation studied under the present conditions is a working heart. A 100-microliter volume constant infusion syringe for time administration of cardioactive drugs may be inserted at the base of the perfusion column to obtain dose-response effects.

Animals↗
PubMed1985

Effects and interactions of natural cannabinoids on the isolated heart.

A Langendorff perfused rat heart preparation was designed to process dose-response effects of cardioactive drugs on rate, coronary flow, and supraaortic differential pressure (delta P; an index of cardiac performance). In this preparation, delta 9- -tetrahydrocannabinol (THC) 2 X 10(-6) M to 10(-5) M induces in the isolated perfused rat heart a biphasic increase in rate (maximal at 8 X 10(-6) M). Tachycardia is associated with decreases in (delta P) and no change or decreased coronary flow. Cardiac toxicity is observed with 3 X 10(-5) M. Cannabidiol (CBD) at concentrations of 9 X 10(-6) M to 10(-4) M has limited effect on rate while increasing delta P and coronary flow. Cannabinol (CBN) 8 X 10(-6) M to 3 X 10(-4) M depresses rate and delta P while coronary flow remains constant. Simultaneous equimolar administration of THC with CBD antagonizes or mitigates the cardiac effects of THC on rate, delta P, and coronary flow.

Animals↗