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56 Abstracts / Toxicology L

Purpose: In Medicine, bruxism refers to the habit of clench-ng and/or grinding the teeth and is a recognized sideffect of several licit and illicit drugs. Particularly for 3,4-ethylenedioxymethamphetamine (ecstasy, MDMA), bruxism is

n almost universal symptom, which explains the propensity ofany MDMA users to seek for this effect as a rough “quality-

ontrol” for the taken pill, and justifies the generalized usef chewing gum, lollipops or even (baby) pacifiers to preventruxism-related deleterious effects in teeth. Methods: In spite ofhe previously reported data concerning MDMA-induced bruxism,mages of related tooth damage do not exist in the scientific liter-ture. In this report, we illustrate this phenomenon. The subjectsere three men of 29, 37 and 40 years old, who were observed in

outine medical consultations at our Forensic Dental Department.hese patients reported long term use of ecstasy (patients 1 and 2)r ecstasy plus cocaine (patient 3), and the habit of clenching and/orrinding the teeth after using these drugs. Results and conclusions ofhe study: Bruxism is an almost universal effect mediated by MDMA.ts detection associated with abnormal behavior and/or MDMA-elated paraphernalia are suggestive of ecstasy abuse that shoulde considered in order to help further rapid toxicological analy-is and therapeutic measures. The mechanism of MDMA inducedruxism is hitherto not fully understood. The interaction betweenopaminergic and serotoninergic neurons is probably implicated

n this effect.

oi:10.1016/j.toxlet.2012.03.221

06-03anaging the new challenges and widening spectrum of

oison Control Centre activities

lavica Vucinic

National Poison Control Centre, Serbia

The National Poison Control Centre (NPCC) is the referentialnstitution in the country, providing the medical services of preven-ion and treatment of poisoning, detection of chemicals in biologicalr other samples, information support for medical personnel andeneral public, scientific research work and education in clini-al toxicology. Objective: To present the organizational structure,esults, activities and new challenges for the NPCC. Methods: Annualesults analysis of the NPCC organizational parts. Results: Theange of NPCC activities is constantly increasing (2078–3996 ptsn 2000 and 2010, respectively; 15,000–18,196 toxicological anal-ses; 10–40 experimental studies; toxicological expertises). Serbia,s a country with the accession perspective, has a vital interest totraightly harmonize its legal system with the EU. Thus the NPCCas been included in the Twinning program with Slovenia, in ordero provide the expert support in the implementation of a Chemical

anagement System. An important element is the necessary safetynformation flow through the supply chain from the producer tohe final user and finally, to the NPCC, where it will be used inhe assembly of the source database for dossiers of chemical sub-tances, formulations and prevention and treatment of poisoning.he NPCC has important role in the National Strategy for emergencyituations, so we have initiated the national project, including 30ospitals in order to provide the national stockpile of antidotes,hich is still unavailable. NPCC is facing new challenges which

equires new legislation policy, technological renovation, but most

f all the enduring enthusiasm of toxicologists.

oi:10.1016/j.toxlet.2012.03.222

211S (2012) S43–S216

P06-04The comparison of the blood mercury in hypertensive andnormotensive patients in Tehran hospitals

Azam Bakhtiarian, Mahmoud Ghazi-Khansari, Abbas Mohaghegh,Vahid Nikoui

Tehran University of Medical Sciences, Iran

Purpose: Hypertension is a very common health problem thatcan cause end organ injuries and even death. There are some evi-dences that high blood level of heavy metals like mercury can causerise in blood pressure. Our objective was to compare the blood mer-cury levels in hypertensive and normotensive patients. Methods:This case–control study was performed in Tehran Heart Center andShariati hospital, Tehran, Iran, on 244 patients aged 40–80 yearswho participated in physical examinations conducted in 2006. Weselected 112 normotensive patients who had no history of essen-tial hypertension and 112 patients who had essential hypertension;then the range of blood mercury levels were measured with Flameatomic absorption. Result and conclusion: Measured blood mercurylevels were in range of 0–39.55 �g/dL. The mean blood mercurylevel in hypertensive patients (10.75 + 1.23 �g/dL) was higher thanthat of normotensive patients (1.6 + 1.02 �g/dL). There was a signif-icant difference in mean blood mercury level in normotensive men(1.74 + 1.56 �g/dL, n = 60) in comparison to that of hypertensivemen (11.9 + 1.38 �g/dL, n = 56). The mean blood mercury level ofnormotensive women (1.5 �g/dL, n = 52) was also significantly dif-ferent from that of hypertensive women (9.65 + 0.53 �g/dL, n = 56).

doi:10.1016/j.toxlet.2012.03.223

P06-05Potential effects of non-conjugated metabolites of propofol inclinical variables

Sónia Campos 1, Aura Silva 2, Paula Pinho 3, Maria Bastos 3, PaulaBranco 4, Luisa Ferreira 4, Luis Antunes 1

1 UTAD/IBMC, Portugal, 2 UTAD, Portugal, 3 REQUIMTE/UP, Portugal,4 UNL, Portugal

Purpose: The transformation of propofol (2,6-diisopropyl-phenol) in 4-hydroxypropofol (2,6-diisopropyl-1,4-quinol) is animportant pathway in the metabolism of this drug, either forhumans and animals. This metabolite is suspected to have one-thirdof the hypnotic activity of propofol (Simons et al., 1991). In thisstudy, the relationship between propofol and its non-conjugatedmetabolites (2,6-diisopropyl-1,4-quinol and 2,6-diisopropyl-1,4-quinone) with clinical variables was explored. Methods: Six NewZealand White rabbits were anaesthetized with three consecu-tive propofol infusion rates (70, 100 and 130 mg kg−1 h−1), eachmaintained during 30 minutes, in a random order for each animal.In the awake animals, at 20, 25 and 30 min after the beginningof each infusion rate and in recovered animals, mean arterialblood pressure (MABP), stages of depth of anaesthesia (DoA) (Silvaet al., 2011) and arterial blood samples were measured. Propofoland propofol non-conjugated metabolites were quantified by GasChromatography/Ion Trap-Mass Spectrometry (GC/IT-MS) assayand their correlation with these clinical responses was analysed.Results and conclusion: The analysed clinical responses showed

a better correlation with propofol non-conjugated metabolites(rMABP = −0.786; rDoA = 0.851, for P values <0.01) than with propo-fol itself (rMABP = −0.651; rDoA = 0.603, for P values <0.01). Theseresults suggest that propofol non-conjugated metabolites may have

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ome hypnotic and haemodynamic depressant effects and/or maymplify the propofol effects during anaesthesia.

eferences

imons, P.J., et al., 1991. Species differences in blood profiles, metabolism and excre-tion of 14C-propofol after intravenous dosing to rat, dog and rabbit. Xenobiotica21 (10), 1243–1256.

ilva, A., et al., 2011. Performance of anesthetic depth indexes in rabbits underpropofol anesthesia: prediction probabilities and concentration–effect relations.Anesthesiology.

oi:10.1016/j.toxlet.2012.03.224

06-06valuation of quetiapine therapy in patients with generalizednxiety disorder

aniela Ionescu 1, Cristina Dehelean 1, Simona Funar-Timofei 2,lena Galca 3, Raluca Dumache 1, Codruta Soica 1

University of Medicine and Pharmacy, Romania, 2 Romaniancademy, Romania, 3 Psychiatry Hospital, Romania

Purpose: Generalized anxiety disorder (GAD) represents ahronic mental disorder associated with significant morbidity andisability. Traditional therapies are associated with poor levels ofemission, and often result some side effects. Methods: Our studyas made along the 12 week (June 2011–September 2011) with aexible dose to assess the efficacy and tolerability of quetiapine asn adjunctive treatment to traditional medication. 60 outpatientsith GAD who had not achieved remission following at least 8eeks of an adequate dose of traditional therapy were enrolled.

he primary endpoint was the mean change from pre-treatmento week 12 in the Hamilton Anxiety Rating Scale (HAM-A) totalcores. Secondary endpoints included: the proportion of patientschieving remission (HAM-A total score of ≤10 at week 12), Clinicallobal Impressions-Severity of Illness, Clinical Global Impressions-lobal Improvement and Penn State Worry Questionnaire. Resultsnd conclusion: Adjunctive quetiapine (mean dose 368 mg/day)ignificantly reduced the HAM-A total scores from pre-treatment28.7 ± 5.4) to week 12 (9.2 ± 8.6).

oi:10.1016/j.toxlet.2012.03.225

06-07habdomyolysis in acute poisonings: 229 hospitalized patients

nezana Jankovic, Jasna Jovic-Stosic, Silva Dobric, Slavica Vucinic

Military Medical Academy, Serbia

Purpose: The purpose of this study is to determine the inci-ence, etiology and clinical course of rhabdomyolysis in theatients with acute poisoning. Methods: We evaluated the hos-ital charts of 972 patients treated from January 1 to December1, 2009. According to PSS score, all poisoned patients with rhab-omyolysis were classified into groups: with mild-creatine kinaseCK) 250–1500 U/L, moderate (CK 1500–10,000 U/L) and severehabdomyolysis (CK > 10,000 U/L). Results: Out of 811 poisonedatients, rhabdomyolysis occurred in 229 (27%) patients (122 male;ge mean, 40 years). Mild, moderate and severe rhabdomyoly-

is had 145 (63%), 77 (34%) and 7 (3%) patients, respectively.ost common were drugs (60%), rather psychotropic drugs (52%

ases – benzodiazepines 28%, antipsychotics 8%, carbamazepine%, antidepressants 4%), then opiates 10%, corrosives 7%, pes-

211S (2012) S43–S216 S57

ticides 5%, poisonous mushrooms 4%, ethanol 3%, toxic gasesfrom fires (2%) and carbon monoxyde (1%), Datura stramonium,colchicines and lead, very rare. Severe rhabdomyolysis was causedby 2,4-dichlorophenoxyacetic acid, opiates alone or combined withbenzodiazepine (two cases), multiple drug intake (benzodiazepinesand atypical antipsychotics) and illicit psychoactive substanceuse. Total of 12% patients developed acute renal failure (ARF),mostly due to toxicity characteristics, except in combined drugs(moderate) and two (severe rhabdomyolysis) heroin-overdose pre-dominantly rhabdomyolytic. ARF, latest with fatal outcomes. Deathwas noted in 60% ARF patients and in 13% all rhabdomyolyticpatients. Conclusion of the study: Rhabdomyolysis is common inacute poisonings, mostly caused by psychotropic agents. Aggressivetherapy is necessary.

doi:10.1016/j.toxlet.2012.03.226

P06-08Relevant toxicokinetic and dynamic differences inecstasy-induced toxic effects

Laura Hondebrink, Saskia Rietjens, Jan Meulenbelt

University Medical Center Utrecht, Netherlands

Purpose: Despite >2000 published articles on ecstasy (MDMA)it remains unclear which mechanisms are most relevant for acuteintoxications and treatment. Triage and treatment of intoxicatedpatients is complicated by variability in clinical effects and couldimprove through insight in interindividual differences in MDMAtoxicokinetics and dynamics. Approach: A comprehensive search inPubMed was performed of all published articles regarding MDMA.Findings: Several enzymes are involved in MDMA metabolism andalthough CYP2D6 is the main phase I enzyme, CYP3A4 also seemsimportant. Low CYP2D6 activity polymorphisms reduce MDMAmetabolism and increase MDMA levels. Polymorphic-induced lowactivities of phase II enzymes likely enhance MDMA-induced tox-icity via accumulation of highly reactive MDMA metabolites andsubsequent oxidative stress which increases even further by auto-oxidation of accumulated neurotransmitters. Co-ingestion of otherxenobiotics may cause inhibition or induction of enzymes involvedin MDMA metabolism and consequently may influence MDMAtoxicity. Neurotransmitter transporters and receptors involvedin toxicodynamic brain effects are also polymorphic expressed,contributing to variable MDMA-induced clinical effects. Further-more, co-exposure to serotonergic drugs increases the risk for theserotonin syndrome, a serious clinical complication. Implications:Specific combinations of polymorphisms increase susceptibility forMDMA-induced toxicity. The relevance of polymorphisms in phar-macokinetics and dynamics should be investigated by genotypingindividuals with a clinically severe MDMA intoxication. Researchshould focus on translating knowledge on mechanisms of actioninto implementation for clinical toxicology. For example, treatmentof ecstasy-intoxicated patients can be optimized when the individ-ual vulnerability due to polymorphisms, tolerance and concomitantdrug use is known.

doi:10.1016/j.toxlet.2012.03.227

P06-09Methylphenidate exposure: What is the risk?

Saskia Rietjens, Laura Hondebrink, Jan Meulenbelt, Irma de Vries

University Medical Center Utrecht, Netherlands