Effect of acute and chronic psychostimulant drugs on redox status, AP-1 activation and pro-enkephalin mRNA in the human astrocyte-like U373 MG cells.

In order to approach the astroglial implication of addictive and neurotoxic processes associated with psychostimulant drug abuse, the effects of amphetamine or cocaine (1-100 microM) on redox status, AP-1 transcription factor and pro-enkephalin, an AP-1 target gene, were investigated in the human astrocyte-like U373 MG cells. We demonstrated an early increase in the generation of radical oxygen species and in the formation of 4-hydroxynonenal-adducts reflecting the pro-oxidant action of both substances. After 1 h or 96 h of treatment, Fos and Jun protein levels were altered and the DNA-binding activity of AP-1 was increased in response to both substances. Using supershift experiments, we observed that the composition of AP-1 dimer differed according to the substance and the duration of treatment. FRA-2 protein represented the main component of the chronic amphetamine- or cocaine-activated complexes, which suggests its relevance in the long-term effects of psychostimulant drugs. Concomitantly, the pro-enkephalin gene was differently regulated by either 6 h or 96 h of treatment. Because astrocytes interact extensively with the neurons in the brain, our data led us to conclude that oxidation-regulated AP-1 target genes may represent one of the molecular mechanisms underlying neuronal adaptation associated with psychostimulant dependence.

[Neocodion misuse: evolution between 1992 and 2002]. / 10 ans de détournement d'usage du Néocodion entre 1992 et 2002.

Neocodion, a codeine antitussive preparation (codeine camphosulfonate + Grindelia + sulfogaiacol) is known to be misused by opiate addicts. This study aimed to examine the evolution in Neocodion use between 1992 and 2002. Since 1992, three surveys (1992, 1997 and 2002) investigating Neocodion misuse were performed via several community networks of pharmacists. During the same time, data on Neocodion use were extracted from the French drug-dependence monitoring programme (OPPIDUM [Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse]). A marked and continuous decrease in Neocodion consumption was observed. The number of requests for Neocodion per pharmacy and per week largely decreased from 9.9 to 2.1 between 1992 and 2002. OPPIDUM data also showed a reduction in the rate of Neocodion consumption (from 8% in 1992 to 0.4% in 2002). Patients were older (30.4 years in 1992 and 33.7 years in 2002) and their socioeconomic conditions were better. Eighty-six percent of the subjects studied were poly-drug consumers. In fact, Neocodion was less sought after for opiate maintenance than for its psychoactive effects. Despite the reduction in the consumption of Neocodion, the changes observed in the consumption patterns for this medication suggest that vigilance is still required.

Spectrum of acute allergic diseases in an emergency department: an evaluation of one years' experience.

OBJECTIVE: There is limited available literature on the incidence of allergic diseases in ED. The objective of this study was to investigate the clinical records of patients admitted to the ED with a suspected allergic reaction. METHODS: A 1 year retrospective study was carried out and data were collected from the patients' computerized medical reports. RESULTS: A total of 324 patients were admitted for an allergic event. Of those, 165 patients (50.9%) were female and their mean age was 55 +/- 18.5 years. Diagnoses included: asthma in 100 patients (30.9%); hymenoptera allergy in 78 patients (24.1%); food allergy in 31 patients (9.5%); drug allergy in 25 patients (7.7%); and allergic conjunctivitis in 12 patients (3.7%). No diagnosis was found in the medical records of 78 patients (24.1%). Anaphylactic shock was observed in 12 patients (3.7%) with a diagnosis of food allergy (six cases), drug allergy (three cases) and hymenoptera allergy (three cases). Ninety patients (27.7%) were hospitalized in the following units: 38 in allergy unit (42.2%); 20 in intensive care unit (22.2%); 10 in pulmonary unit (11.1%); eight in the dermatology unit (8.9%); six in the internal medicine unit (6.7%); and eight in other units (8.9%). Overall, 42 patients (12.9%) were evaluated by an allergologist after ED discharge with positive allergy results in 28 cases (66.6%). CONCLUSIONS: Acute allergic diseases are not rare in ED, representing 1% of the annual visits in our series. A low rate of allergologist referral was observed. Emergency physicians must work closely with allergologists to ensure a better evaluation, long-term care and preventive management of patients with allergic diseases admitted to the ED.

Constitutive nitric oxide synthase inhibition combined with histamine and serotonin receptor blockade improves the initial ovalbumin-induced arterial hypotension but decreases the survival time in brown norway rats anaphylactic shock.

Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.