Non accidental repeated lithium poisoning in a child: The role of hair analysis.

Non accidental intoxication due to child abuse is rare and its frequency is likely underestimated because it is difficult to diagnose. Here, we report a case of voluntary repeated exposure to lithium in an infant, for whom the clinical manifestations were convulsions. Toxicological analysis was very helpful for documenting lithium exposure during the assumed period of time. Interpreting the results of hair analysis, a simple and minimally invasive examination, is tricky at this age, but it can facilitate the differentiation of acute versus chronic exposure. Although infrequent and underestimated, lithium should be considered as a cause of intoxication in a previously healthy child with acute seizure.

[Focus on the endocannabinoid system and the reprotoxicity of marijuana in female users]. / Focus sur le système endocannabinoïde et la reprotoxicité du cannabis chez la femme à l'heure du débat sur sa dépénalisation en France.

Among recreative compounds, marijuana is the most used worldwide. Delta9THC binding on brain endocannabinoid receptors drives its psychotropic effects. The endocannabinoid system (ECS) is an endogenous neurohormonal system essential for homeostasis composed of ligands, metabolic enzymes and at least 2 receptors discovered to date. In female reproduction, the ECS regulates the hypothalamic-pituitary axis and many steps of the reproduction process, such as ovulation, tubal transportation and trophoblast implantation. Delta9THC can cross the placental barrier and bind to the fetal endocannabinoid system. In humans, fetal and obstetrical consequences of marijuana use during pregnancy are intrauterine growth restriction and preterm delivery. In the light of legalization projects currently reviewed in several western countries, further research should be conducted to improve knowledge on maternal, fetal and reprotoxic consequences of marijuana use during reproductive age and pregnancy.

Caffeine-induced modifications of heart rate, temperature, and motor activity circadian rhythms in rats.

Even if the effects of caffeine on some physiological parameters are well known, its influence on circadian rhythmicity had not yet been investigated. This possible influence is of particular importance, introducing a possible bias in chronopharmacological studies. Thus, the aim of this study was to evaluate the effects of repeated caffeine administration on the circadian rhythms of heart rate "H," body temperature "T," and motor activity "A" in unrestrained rats maintained under controlled conditions (LD 12:12, light from 0600 to 1800 h) by using radiotelemetry transmitters. The study was divided into three 7-day observation spans: a 1-week control span "P1," a 1-week treatment span "P2," and a 1-week recovery span "P3." P1 was performed for assessing baseline measurements of H. T, and A. During P2, four rats received caffeine (25 mg/kg) at 0900 h, while four rats received saline in the same conditions every day of the observation span. H, T, and A were continuously monitored and plotted every 10 min. For P1, P2, and P3. a power spectrum analysis (Fourier transform) was applied to determine the dominant period of rhythmicity. If H, T, and A circadian rhythms were detected, the characteristics of these rhythms, i.e., mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means +/- SEM and compared by analysis of variance. Our results indicated that caffeine did not suppress the circadian rhythmicity of H, T, and A, but significantly increased mesors and decreased amplitudes of the three rhythms and advanced acrophases of temperature and activity compared to the control group.

Evaluation of biological stress markers in police officers.

This study was performed on 18 police officers, in order to evaluate relations between behavior and the activity of the main hormonal systems implicated in stress management. All subjects were male volunteers with more than 2 years on the job, a type A psychological profile according to Friedman and Rosenman, suffering from no mental or physical illness. The experimental setting used to study the role of different stress factors consisted of a series of tests that re-created stressful situations that the subject might encounter in his job. The study showed that during stressful states, not only did peripheral secretion of catecholamines increase, but that the ratio of epinephrine to norepinephrine was a determinant factor. Epinephrine secretion which was elevated at the beginning, decreased when the stressful situation was clarified or controlled, whereas norepinephrine secretion remained elevated as long as the subject had to remain alert. Cortisol secretion seemed to depend upon anticipation of the stressful event more than its actual happenning.

Chronopharmacological effects on nicotine repeated administration on heart rate, body temperature and locomotor activity circadian rhythms in rats.

The aim of this study was to compare morning and evening repeated nicotine administration on the circadian rhythms of heart rate (H), body temperature (T) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. The study was divided into three 7-day periods: a control period (P1), a treatment period (P2) and a recovery period (P3). During P2, four rats received nicotine (1mg.kg(-1)) subcutaneously at 09.00 h and four rats received nicotine in the same conditions at 21.00 h. For P1, P2 and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. If H, T and A circadian rhythms were detected, the characteristics of these rhythms were determined by cosinor analysis, expressed as means+/-SEM and compared by ANOVA. Our results indicated: (1) a lack of detection of A circadian rhythm during P2 for the morning group while H and T circadian rhythms were detected for the morning and evening group whatever the period. (2) alterations of mesors, amplitudes and acrophases of H and T circadian rhythms for the morning and evening group during P2 and alterations of mesor, amplitude and acrophase of A circadian rhythm for the evening group. Furthermore these alterations were significantly different for the morning and evening group during P2. These results showed that the time of administration of nicotine differently affect H, T and A rhythms. The authors suggest that these effects can be mediated by central cholinergic and/or monoaminergic mechanisms.

Nicotine-induced perturbations on heart rate, body temperature and locomotor activity daily rhythms in rats.

The aim of this study was to evaluate the influence of nicotine on the daily rhythms of heart rate, body temperature and locomotor activity in unrestrained rats by use of implanted radiotelemetry transmitters. The study was divided into three seven-day periods: a control period, a treatment period and a recovery period. The control period was used for baseline measurement of heart rate, body temperature and locomotor activity. During the treatment period three rats received nicotine (1 mg kg(-1), s.c.) at 0900 h. Three rats received saline under the same experimental conditions. Heart rate, body temperature and locomotor activity were continuously monitored and plotted every 10 min. During the three periods a power spectrum analysis was used to determine the dominant period of rhythmicity. If daily rhythms of heart rate, body temperature and locomotor activity were detected, the characteristics of these rhythms, i.e. the mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means +/- s.e.m. and compared by analysis of variance. Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity. These perturbations might result from the effects of nicotine on the suprachiasmatic nucleus, the hypothalamic clock that co-ordinates biological rhythms.

Prevalence of drugs of abuse in urine of drivers involved in road accidents in France: a collaborative study.

The collaborative, anonymous, case-control study was intended to determine the prevalence of opiates, cocaine metabolites, cannabinoids and amphetamines in the urine of drivers injured in road accidents and to compare these values with those of non-accident subjects ("patients") in France. Recruitment was performed nationwide in the emergency departments of five hospitals and comprised 296 "drivers" aged 18 to 35 and 278 non-traumatic "patients" in the same age range. Females represented 28.4% of "drivers" and 44.2% of "patients." Screening for drugs in urine was performed by fluorescence polarization immunoassays in each center. Each positive result was verified using gas chromatography-mass spectrometry (GC-MS), in a single laboratory. Statistical analysis comprised single-step logistic regression and simultaneously took account of confounding factors and the final differences in prevalence values between the two populations or different subgroups. Cannabinoids were found in 13.9% of drivers (16.0% of males and 8.3% of females, p < 0.05) and 7.5% of patients (12.3% of males, 1.6% of females, p < 0.0001); only in females was this prevalence higher in injured drivers than in patients (p < 0.05). Opiates were present in 10.5% of drivers' and 10.4% of patients' urine samples (NS), and were more frequent in urine samples positive for cannabinoids, in drivers (p < 0.01) as well as in patients (p < 0.001). The prevalence of cocaine metabolites in drivers and patients was 1.0 and 1.1% and that of amphetamines 1.4 and 2.5%, respectively. No causal relationship between drugs and accidents should be inferred from this retrospective study. Nevertheless, the high prevalence of cannabis and opiate (licit or illicit) use in young people, whether injured drivers or patients, has potential implications for road traffic safety in France. Cocaine and amphetamines did not appear to be a major problem, unlike the experience in other countries.

Comparison between micronucleated lymphocyte rates observed in healthy subjects and cancer patients.

Micronucleated cell rates were assessed in cytokinesis-blocked lymphocytes of 198 male and female healthy subjects (HS) not occupationally exposed to genotoxic risks and of 70 male and female cancer patients (CP) prior to any anticancer treatment. In the HS group, spontaneous micronucleated cell rates (MN cell rates) were 9.7 +/- 2.8 per 1000 binucleated lymphocytes and 9.8 +/- 3.1 for males and females respectively. In the CP group, spontaneous MN cell rates were 21.1 +/- 15.3 per 1000 binucleated lymphocytes and 19.1 +/- 11.2 for males and females respectively. Moreover, they were shown to have a large inter-individual variability in the two groups. The study of inter-individual variation factors showed that only tobacco could affect MN cell rate in HS whereas age and sex apparently had no significant effect. In the CP group, only age significantly affected MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. There was no significant difference in the distribution of gender between HS and CP, whereas there was a significant difference in the distribution of age and tobacco between the two groups. The comparison of MN cell rates in 54 HS and 54 CP matched for age and sex showed a statistically significant difference. Spontaneous MN cell rates of these two populations reflect environmental exposure. Moreover, for CP it most probably refers to various cellular lesions and genetic damage.

Evidence of pin implantation as a means of verifying death during the Great Plague of Marseilles (1722).

The evidence obtained for the methods used in verification of death during the Great Plague of Marseilles in 1722 is presented here. This evidence was gathered during the excavation of a mass grave dating from this epidemic, and is based on two adjacent interments. The technique used at that time was the implantation of bronze pins into the toes. This method is precisely described in the medical treatises dating from this period, which list different death verification methods. The fear of "false death" and the burial of still living people characterized the end of the 17th and the 18th centuries. It should be noted that the main cause of apparent death is presented in the same medical treatises as the plague. This observation is the first anthropological evidence of the use of this forensic method to verify the fact of death.

Daily rhythms of heart rate, temperature and locomotor activity are modified by anaesthetics in rats: a telemetric study.

The aim of this study was to evaluate the effect of anaesthesia (ether or ketamine) on daily rhythms of temperature (T), heart rate (H) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. T, H and A were measured every 10 min, in Wistar male rats, and analysed using Cosinor. The mean +/- SEM days needed, after surgical implantation, to detect a daily rhythm in H, T and A were also assessed. Six rats were anaesthetized for about 50 min either by ketamine or ether in a 3 by 3 cross-over design. Mesors, amplitudes and acrophases of T, H and A were calculated three days before (D-3; D-2; D-1), the day of anaesthesia (D0) as well as the three following days (D1; D2; D3). ANOVA was performed in order to detect, firstly a possible effect due to the order of application of anaesthesia, secondly a significant difference between ether or ketamine-induced anaesthesia and finally a modification of the mesors, amplitudes and acrophases of T, H and A, induced by each anaesthesia, for D0, D1, D2 and D3 when compared to D-1. Our results indicate: (1) Alterations of the acrophases, mesors and amplitudes, except for the amplitude of A, of the daily rhythms of T, H and A on D0 of ketamine anaesthesia while regarding ether anaesthesia only amplitude of T and H and acrophase of A were modified on D0. Some of these modifications were still observed on the days following anaesthesia. A significant difference between ether and ketamine-induced anaesthesia was also observed. (2) A non-detection of T, H and A daily rhythms after surgical implantation, which was not observed after injection of either ether or ketamine alone. Almost 10 days were needed to detect a significant daily rhythm for T, H and A. The authors suggest that, the general anaesthetic agent was responsible for a perturbation of the mesors, amplitudes and acrophases of the daily rhythms of H, T and A while the non-detection of these rhythms after implantation was more due to the surgical aggression.

[Cannabis: toxicokinetic focus and methodology of urinary screening]. / Le cannabis: mise au point toxicocinétique et méthodologie du dépistage urinaire.

Cannabis is the most commonly used illicit drug in the world. The major psychomimetic compound is delta 9-tetrahydrocannabinol. The major effects consist in alterations of sensory perception, cognition, motor coordination and self-perception. Procedures designed to detect cannabis use have been developed since 1988. The traditional approach is to screen urine by immunoassay and to submit positive samples for confirmation by gas chromatography and mass spectrometry. There continue to be many difficulties in interpreting the results because of the biotransformations of delta 9-tetrahydrocannabinol.

[Application of micronucleus test for the demonstration of antimutagenic properties of natural substances]. / Application du test des micronoyaux à la mise en évidence des propriétés antimutagènes de substances naturelles.

Authors have used a reliable and reproductible original model of controlled production of free radicals for the cytokinesis-block micronucleus assay. This mutagenicity test is of easy realization and quick interpretation. An experimental model is proposed to test mutagenic activity of free radical generators and antioxydant properties of many substances, such as ascorbic acid. Its addition to the culture medium showed a significant decrease in the rate of micronucleated cells exposed to the free radical generator. The study of other antioxydant compounds (beta-caroten and 5-hydroxyquinolin) have confirmed results previously obtained with ascorbic acid. Thus, the free radical generator coupled to the cytokinesis-block micronucleus assay represents a reliable test to study and evaluate the antioxydant power of natural substances.

Tobacco smoke influence on heart rate, body temperature, and locomotor activity daily rhythms as assessed by radiotelemetry in rats.

Using radiotelemetry, this study aimed to evaluate the influence of tobacco smoke on heart rate (H), body temperature (T) and locomotor activity (A) daily rhythms in rats. The tobacco smoke intoxication was produced with a smoking apparatus. H, T, and A data were captured by radiotelemetry. The study was divided into three periods: a 1-week control period (P1), a 1-week stress period (P2), in order to evaluate the stress induced by the animals' restraint in the smoking apparatus, and a 1-week daily tobacco smoke intoxication period (P3). For P1, P2, and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. Then, characteristics of the rhythms were determined by cosinor analysis. Statistical comparisons were done by ANOVA. Power spectrum analysis showed that neither stress nor tobacco suppressed the daily rhythmicity. Cosinor revealed some modifications: H amplitude was decreased during P2 and P3 with a greater reduction during P3, while T and A amplitudes were decreased during P2 and P3 without difference between P2 and P3. T acrophase was delayed during P2, while A acrophase was delayed during P2 and P3 without any difference between P2 and P3. These perturbations may reflect the effects of stress and tobacco on the suprachiasmatic nucleus by a dopaminergic mechanism.

[The Ames test: application to smokers' urine]. / Le test d'Ames: application aux urines de fumeurs.

The Ames test is a rapid and sensitive in vitro technique for detecting mutagens by using Salmonella typhimurium hypersensibilized strains. We applied this assay to the study of smoker's urine mutagenicity. Eighteen smokers and 18 non-smokers were investigated. Statistical analysis showed a significant increase of the smoker's urine mutagenicity. The Ames test could be used to determine the mutagenicity level of smokers. Moreover, the results suggest the applicability of the Ames test to urines of ex-smokers and passive smokers.

[Urinary screening of drugs of abuse among drivers involved in road accidents]. / Le dépistage urinaire des psychotropes illicites chez les conducteurs de véhicules accidentés.

Driving under the influence of drugs is a growing cause of traffic injuries. Therefore the Abbott Laboratories established a study to estimate the consumption of opiates, cannabinoids, cocaine and amphetamines among young adults involved in a road accident and to compare with a control group. Analytical procedure chosen include an anonymous collection of urines. Drugs are screened by fluorescence polarization immunoassay. Positive samples are confirmed by gas chromatography/mass spectrometry. Results do not show any difference between the two groups.