Journal de toxicologie clinique et experimentale最新文献

Tiapride, a benzamide compound, is a neuroleptic drug used in the treatment of some behavior troubles, especially in the alcohol withdrawal syndrome. We report a new case of malignant neuroleptic syndrome during a tiapride treatment in a 39 year-old alcoholic patient who had been admitted after a minor trauma. Symptoms were typical, with malignant hyperthermia in the absence of sepsis, coma, extrapyramidal syndrome, rhabdomyolysis, and severe metabolic acidosis. Dantrolene succeeded to reverse hyperthermia and rigidity; probably due to its delayed administration however, irreversible acidosis led to the patient's demise.

In vitro studies have suggested that peripheral binding sites (PBR) for benzodiazepine (BZD) could be coupled to the voltage operated calcium channel (VOC) in the heart and that PK11195, an non-BZD ligand with antagonistic activity at this receptors, could inhibit the electrophysiological and mechanical properties of both "peripheral" benzodiazepines and calcium channel blockers. This study evaluates the antidotal value of PK11195 against the cardiovascular depression and arrhythmias in a canine model of acute verapamil intoxication. Although sinus activity is more often preserved or restored (7/8 vs 1/6) in the animals treated with PK11195, this compound, administered in doses able to saturate heart PBR, is unable to prevent or correct the haemodynamic alterations induced by acute verapamil intoxication and the improvement of survival (8/8 vs 3/6) is not significant.

A case of Flumequine poisoning is described; a 13-year-old girl was admitted for a psychiatric syndrome. 3 hours after, seizures, coma, and metabolic disorders were observed. Infectious, encephalitic or diabetic diseases were suspected, but not confirmed. After 12 hours of a symptomatic treatment, the clinical status improved and the patient was discharged. At that time a tablet was found in her bedroom and a mas spectrographic analysis was positive for Flumequine. This case report is in agreement with previous observations and confirms the small therapeutic index of quinolone, and the absolute necessity to assess carefully a psychiatric diagnosis.

The influence of 5 days' triiodothyronine (T3) administration (0,1 mg/kg/day) on myocardial uptake kinetics and electrocardiographic effects of amiodarone (4,7 10(-6)M) were examined in isolated perfused rabbit hearts. Pharmacokinetic parameters were determined by plotting the coronary sinus effluent amiodarone concentration time-data. Electrocardiographic effects were measured as percentage changes in PR, QRS and QT electrocardiogram intervals measured in hearts removed from T3 pretreated rabbits. The perfusion of normal rabbit hearts with a modified Krebs Henseleit buffer containing amiodarone prolonged PR, QRS and QT intervals by 74%, 76% and 14% respectively, while in T3 pretreated rabbit hearts, amiodarone induced a prolongation of 84% PR, 27% QRS and 9% QT. Myocardial amiodarone accumulation normalized for heart weight represented myocardial concentrations of 260.6 +/- 20.9 micrograms/g and 235.6 +/- 11.9 micrograms/g of tissue respectively in the normal and T3 pretreated groups after a 60 min perfusion. The relationship between myocardial amiodarone concentration and electrocardiographic effects on PR and QRS were linear in both groups. The data demonstrate that the thyroïd hormone T3 did not change the kinetics of the myocardial uptake of amiodarone, but that it did change the electrocardiographic effects. Although T3 potentialized the amiodarone effect on PR, it reduced its effect on intraventricular conduction and ventricular repolarisation.

This study was initiated to investigate the long term effect of exposure to organophosphorus pesticides (O.P), with consideration to bilharziasis (an endemic parasitic disease in Egypt, usually associated with liver fibrosis). Serum levels of choline esterase (Ch E), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (Alk. Ph.) and proteins were estimated among 100 (O.P.) sprayers with various duration of exposure (3 to 15 years) and among 60 controls. O.P. sprayers showed significantly higher, SGPT and Alk. Ph. and lower Ch E and serum proteins than the controls. Among sprayers, duration of exposure to O.P. was significantly correlated with their levels of Ch E, SGPT, and Alk. Ph. but not with serum proteins. Compared to other parameters, SGPT seems to be a good indicator of the hepatic effect of long term exposure to O.P. Bilharzial infection did not modify the effect of O.P. pesticides on the above mentioned parameters. Ch E of smoker sprayers was significantly less than that of non smokers. This was attributed to increased absorbtion of O.P. during smoking at work places.

The catabolism of tRNA gives rise to modified nucleosides, among which pseudouridine, which are excreted in urine. An increased cell turnover is associated with an enhanced excretion of these products. Some authors have also reported an increased urinary excretion of pseudouridine in asbestos workers without clinical signs of malignancy. In two experimental models of carcinogenesis (i.e. injection of Lewis carcinoma cells in C57/B1C mice and oral administration of 7,12 dimethyl-benz(a)anthracene in female Sprague-Dawley rats), we have confirmed that the occurrence of the tumor is associated with an increased urinary excretion of pseudouridine. This metabolic change, however, does not precede the detection of the tumor. In control human subject, no sex and age effect was found in the urinary concentration of pseudouridine. Patients with a malignant disease excrete an enhanced amount of pseudouridine. A pilot study among workers exposed to polycyclic aromatic hydrocarbons in a coke oven did not reveal any change in the urinary concentration of pseudouridine.

The toxic effect of 84 essential oils was tested at different concentrations on Entamoeba histolytica. 15 of them were the most efficient. 5 of the latter were detailed to give the percentages of their components. Some families of plants have shown an homogeneity in the toxicity of their essential oils, while others, to the contrary, have presented heterogeneous amoebicidal activities. Further investigations should be made to identify amoebicidal effects of essential oils in vivo.

The aim of this study is to determine the efficiency ot toxicologic screening (detection of barbiturates, benzodiazepines, tricyclic antidepressants, salicylates, phenothiazines, meprobamate and ethanol assay), during acute drug poisoning. In 1988, 898 patients are enclose in this study. Screenings are negative in 17% of cases; benzodiazepines, alcohol and antidepressants are often found. The recovery is very good for barbiturates and salicylates but it's not perfect for benzodiazepines, particularly flunitrazepam triazolam, loflazepate, oxazepam, and non tricyclic antidepressants. This failure probably depends on these emergency methods.

This study investigates the effects of three successive cisplatin administrations to rats on liver cytochrome P-450 and some related specific catalytic activities. Additionally, because glutathione and its related enzymatic system are significantly involved in cellular detoxification process, we examined the effects of cisplatin on lipid peroxidation, glutathione levels, glutathione reductase and peroxidase activities. Cisplatin induced a decrease of cytochrome P-450, glutathione-S-transferase and some cytochrome P-450 related specific catalytic activities among which aminopyrine demethylase and benzo(a)pyrene hydroxylase activities are representative of cytochrome P-450b and P-450h isoforms. Furthermore, cisplatin-induced N-glucuronyl transferase and lipid peroxidation which might participate, at least in part, in cisplatin-induced hepatotoxicity. The ability of cisplatin to cause alterations in the activity of other enzymes than those of cytochrome P-450 system suggests that cisplatin induces toxic effects in an unspecific manner.

Mescaline was extracted from a vegetal powder, seazed on the "Côte d'Azur", then analyzed by several techniques (thin layer chromatography, infra-red spectrometry, gas chromatography/mass spectrometry) and determined by high performance liquid chromatography with methyl-amphetamine as internal standard. The powder contained 0.76% of mescaline. The presence of a possible isomer was noted in the powder as well as in a "old" sample of mescaline.