Journal de toxicologie clinique et experimentale最新文献

The embryotoxicity and teratogenicity of alpha-asarone were investigated in mice. The drug was dissolved in corn oil, and administered daily, by gavage, on days 6 to 15 of gestation, at 0 (controls), 5, 15, 30 and 60 mg/kg. Fetuses were removed on day 18 by caesarean section and examined using routine teratological methods. A significant maternal toxicity was observed in dams given 60 mg/kg, as indicated by a reduced weight gain. An embryolethality was observed in 15, 30 and 60 mg/kg treated groups. In addition, the highest dose induced fetal malformations, mainly represented by hydrocephaly, extra-ribs, clubfeet and cleft lips.

For near thirty years, epidemiological studies have coped with the search of possible noxious consequences of an involuntary exposure of pregnant women to environmental tobacco smoke on the gestation and the intrauterine development of embryo and foetus. These studies were mainly retrospectives; a careful study of the methods used (questionnaires, evaluation of exposure, and so on ...) gives evidence that they can rarely avoid serious criticism. As possible effects of intrauterine exposure to environmental tobacco smoke, low birth weight and impairing of other body parameters, perinatal mortality, frequency of abnormalities have been reviewed. As a potential cause, the role of the father tobacco smoking has been especially examined. As a whole, the consequences of a prenatal exposure to environmental tobacco smoke are an extremely controversial subject and no obvious effect has yet been universally recognized. The critical analysis of the studies has shown that, frequently, the epidemiological studies have been interpreted in order to find links between and involuntary exposure to tobacco smoke and some troubles of reproduction, particularly in offspring. As a matter of facts, fundamentally, the noted actually correlations, even if they are statistically significant, are not able to move such links. They are only able to indicate the existence of an association and only, if the eventual role of confounding factors has been properly treated. An interesting case is the potential effects of the father's tobacco smoking. The hypotheses emerging from these examined inquiries remain to be more precisely defined and thoroughly by new studies, preferentially prospective, and, when necessary, completed by animal experiments. It is suggested that a special effort shall be applied to the measurement of the exposure of pregnant women to define toxic compounds originating from environmental tobacco smoke. Presently, it is not possible to draw a conclusion on the noxious or innoxious influence of the involuntary exposure of pregnant women to environmental tobacco smoke, particularly as far as potential risks for foetus are concerned.

After a chloroform intraperitoneal injection, lactate dehydrogenase, alanine aminotransferase and particularly aspartate aminotransferase serum activities are much more raised in deficient animals. Liver ornithine decarboxylase (ODC) activity normally decreases in rats between the 4th. and the 7th. month after the weaning. In vitamin A deficient animals, basal values of the enzyme activity are lower and the decrease is deeper. But even at month 7, liver sustains a partial capacity of ODC recovery if retinol is fed during 15 days. Chloroform administration strongly enhances liver ODC activity in normal rats. In the deficiency, stimulation is lower in absolute value but relatively higher if referred to basal level. After retinol refeeding, chloroform stimulates enzyme activity to nearly normal values. Vitamin A deficiency impairs obviously liver ODC activity and its response to chloroform stimulation in rats, but the stroke is at least partially reversible in our conditions. Moreover, deficient animals maintain a non negligible capacity of ODC response under chloroform stimulation.

To provide a consistent teratogenic risk assessment from animals' data, the system described here suggests an evaluation by stages. Based on the expert system from Mattison, the toxic responses of common species of experimental animals are scored. The scores are then multiplied by the ratio of the lowest adult 'toxic dose A, to the lowest developmental toxic dose D (A/D). The products form 3 categories. Based on the reversibility of the developmental effects, the categories are subdivided into classes A B C D. This system should permit an unbiased risk assessment and a comparison of industrial chemicals' prenatal toxicity.

Three cases of iodoform poisoning are described following dressings with 10% iodoform gauze (0.10 x 5 m) on extended wounds. Five, ten and sixteen days after the beginning of dressings, the patients became confuse, hallucinated, and one of them was subsequently comatose. Vomiting, fever, tachycardia with premature ventricular beats and shortening of P-R interval, slight increase of transaminases and proteinuria were observed. Within a few days (3 to 8) after the iodoform dressings were discontinued, the signs of iodoform toxicity disappeared. The toxicity of iodoform is probably unrecognized if the rarity of the observations published and the amount of iodoform gauzes annually sold are compared.

The authors report the history of 49 patients, admitted to an intensive care unit after a caustic or corrosive ingestion. This series follows a similar one, related in 1979. An update is made for early evaluation and management, based on patients classification in three groups: severe cases, moderate cases, mild cases. Clinical and biological data, treatment and outcome for the three groups are related. The frequency and gravity of these poisonings appear to be the same as in the first series, with poor prognosis for extreme emergencies and high risk of oesophageal or gastric stricture for important forms. In this population, 20% of extreme emergencies have favorable outcome with early major surgical procedure.

This preliminary study evaluates the cardiac and neurological risks associated with the sudden antagonism of benzodiazepine (BZD)--induced sedation in dogs intoxicated with tricyclic anti-depressants (TCA). Twelve dogs were anesthetized with midazolam and ventilated with room air. EEG, ECG, and arterial pressure were continuously recorded. An infusion of amitriptyline (6 dogs) or clomipramine (6 dogs) 1 mg/kg. min was maintained until signs of cardiotoxicity (QRS prolongation, hypotension or arrhythmias) occurred. The effects of a bolus of flumazenil 0.2 mg/kg were then observed until 120 minutes. In amitriptyline poisoning, BZD reversal was associated with development of convulsions in 3 dogs, with severe arrhythmias in 4 and with one death. In clomipramine intoxication, 2 dogs developed sudden fatal arrhythmias. These results show that BZD reversal may unmask the convulsant properties and increase the severity of arrhythmias induced by TCA.

Lesions by ingestion of corrosive substances had so far been treated at the time of sequelae. In the seventies several events modified deeply the epidemiology and the early care of these poisonings. At that time household products like highly concentrated basic and acid substances and oxidizing agents were distributed and led to an increase of the number and the severity of these intoxications. In the same time, fiberoptic endoscopy of the digestive tract played a leading part to evaluate the diagnosis and the prognosis of these poisonings at an early stage, and thus, with accurate intensive care and digestive surgery contributed to generate appropriate guidelines, according to the severity. The first step of the treatment is fasting, fluid replacement and analgesic if required. A full examination must be performed, especially in the throat even if there is no strong correlation between early clinical signs and the severity of the lesions; blood samples must be obtained to look for metabolic acidosis, hyperleukocytosis hemolysis and consumption coagulopathy which could be better indicators of the severity. Fiberoptic endoscopy of the upper digestive tract should be performed as soon as the physical and psychological patient's condition is stable; if possible before the twelfth hour and no more late than the twenty-fourth hour. It should determine the lesions: type, range and grade according to Quincy's classification modified by Mongon and Di Constanzo. Survival and healing of "extremely severe" grade intoxication can only be obtained through a surgical intervention within the first hours; a laparotomy will indicate the depth of the lesions, which is not determined by endoscopy, and will consist of Celerier's stripping method and if necessary a gastrectomy, more seldom a cephalic duodeno-pancreatectomy. Only the surgical excision of necrotic tissues can prevent the occurrence of lethal complications like oesophageal or gastric perforations and septic shocks. The analysis of the literature from 1975 up to now gives us information on the methods and the results of these different therapeutic approaches.