Suicidal poisoning by verapamil:: Forensic toxicology aspects: A case report

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Z57 The release of analgesic medication A pharmacoepidemiological investigation Oana Teslariu 1,∗ , Liliana Tartau 2 , Elena Teslariu 3 1

University of Medicine and Pharmacy Gr T. Popa, Student, Iasi, Romania, 2 University of Medicine and Pharmacy Gr T. Popa, Department of Pharmacology, Algesiology, Iasi, Romania, 3 University of Medicine and Pharmacy Gr T. Popa, Iasi, Romania Aim: A pharmacoepidemiological analysis on the release of analgesic medication in a pharmacy in Iasi, Romania. Method: This exploratory study was performed in a private pharmacy, during 6 month, consisting of analysis the computerized evidence of the release of analgesic medication. Results: The management of pain is realized especially with association of analgesics: nonsteroidal anti-inflammatory and analgesic antipyretic drugs. A very important observation of our study was that the most analgesic drugs were released without a medical prescription. This study established that metamyzole and acetaminophen were the best sold analgesic drugs in the over count (OTC) form and prescription form. Among the nonsteroidian antiinflammatory, acetylsalicilic acid, diclofenac, ibuprofen have been the most sold analgesics. Our study also shows that two opioid analgesics: tramadol and codeine were released without medical prescription. Conclusion: We observed that there was a large quantity usage of the OTC vs. prescribed analgesic medication. Much more the studies show that in our country the pain of different origin is unclear treated, due to the actual economical and legal restrictions. Keywords: Pain; Analgesics; Nonsteroidal anti-inflammatory drugs; Opioids doi:10.1016/j.toxlet.2008.06.080 Z58 The use of dextromethorphan in young people—A pharmacoepidemiological investigation Liliana Tartau 1,∗ , Elena Teslariu 1 , Oana Teslariu 2

1

University of Medicine and Pharmacy Gr T. Popa, Department of Pharmacology, Algesiology, Iasi, Romania, 2 University of Medicine and Pharmacy Gr T. Popa, student, Iasi, Romania Aim: The research of some aspects regarding the use of dextromethorphan (DXM) in teenagers. Dextromethorphan (d3-methoxy-N-methyl-morphinan) is the dextroisomer of levomethorphan, a semisynthetic morphine derivative, and acts as potent blocker of the N-methyl-d-aspartate receptor. Dextromethorphan abuse has traditionally been with the OTC cough preparations (e.g. Tussin Forte). Its primary use is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation. DXM is often abused in high doses by adolescents to generate euphoria and visual and auditory hallucinations. Material and method: This study represents a pharmacoepidemiological evaluation and it is based on a questionnaire applied to 152 persons with ages between 12 and 23 years, over a period of two weeks. The questionnaire consists of 13 questions regarding age, purpose of using, association with other substances, reasons, quantity and frequency of use. Results: The questionnaire revealed that among the questioned population the use of Tussin Forte is wide spread probably due to

its relative low cost and the ease of obtaining it. The majority of the users are between 16–19 years old and especially male subjects. Almost a half (45%) of investigated youngsters declared monthly intake of substance, in a dose of 15–20 times higher than therapeutic one (60–120 mg/day). DXM dependence is often associated in young people with alcohol and other drugs addiction. The purpose of use, as questionnaire shows, is euphoriant, anxiolytic and analgesic effect. Conclusions: Our study shows that in 79% of subjects DXM is abused for other reasons than antitussive effect. doi:10.1016/j.toxlet.2008.06.081 Z59 Historical control data for carcinogenicity studies—Scientific advantages and values Bipin Trada ∗ , Virendra Tiwari, Darpesh Gohel, Virendrasinh Zala, Pradeep Deshmukh, Rajesh Ugalmugale Jai Reaserch Foundation, Valvada, Gujarat, India To assist interpretation and potential local influences of the laboratory environment, baseline data are very important for lifetime carcinogenicity studies. For the scientific advantages, Jai Research Foundation (JRF) critically evaluated the control data of a rat carcinogenicity study. Specific Pathogen Free (SPF) HsdBrlHan:WIST Wistar rats obtained from Harlan UK Limited were maintained untreated and provided ad libitum autoclaved rodent diet (2018S, Tekland) and UV sterilized charcoal filtered water. A 24-month study was conducted with 50 males and 50 females to investigate survival, growth pattern, general health, clinical pathology and incidence of nonneoplastic and neoplastic lesions. At the end of the study survival was 68% and 66% in males and females, respectively. Clinical observations, body weight, food consumption and clinical pathology were within expected background ranges and comparable to background data at JRF and suppliers, there were no noticeable changes in tumor incidence or type. Information on the carcinogenic potential of a xenobiotic is obtained by assessing tumor incidence in a lifetime study. In the case of unusual or atypical frequencies of lesions, there are certain limitations of the concurrent control data. In such cases historical control data may support the assessment of the potential risk. This current study may provide valuable information for interpretation of carcinogenicity data in the Wistar rat and will provide a baseline for expansion of our database. doi:10.1016/j.toxlet.2008.06.082 Z60 Suicidal poisoning by verapamil Forensic toxicology aspects: A case report Maja Vujovic 1,∗ , Milan Jokanovic 1 , Biljana Milosavljevic 2 , 1 Lidija Kostic-Banovic , Simonida Seskar-Stojancov 3 , Slobodanka Milicevic-Misic 3 1

Faculty of Medicine, Nis, Serbia, 2 Institute of Forensic Medicine, Nis, Serbia, 3 Clinic of Endocrinology, Department of Toxicology, Nis, Serbia Introduction: A 75 years old woman was found by her family members on the bedroom floor in unconscious state and without any blooding wound. Near her body there were empty boxes of verapamil (about 40 tablets), which were prescribed as therapy. After admission on Clinic of Toxicology, her condition was still critical.

Abstracts / Toxicology Letters 180S (2008) S32–S246

Symptoms: unconsciousness, hypotension, bradycardia, atrioventricular block, metabolic acidosis, azotemia, electrolytic disorder and dehydration. She received intensive supportive and antidote therapy. Nevertheless, the old women experienced aggravation with respiratory arrest. She died 3 days after admission. After autopsy the samples of parenchymal organs, blood and urine were send for toxicological and histopathological analysis. Toxicological findings: Verapamil was identified and quantified in all samples by GC/MS technique, in the following concentrations: brain 0.05 mg/kg; stomach 0.11 mg/kg; heart, lung and spleen 0.37 mg/kg; kidney with gall bladder 0.06 mg/kg; liver 0.13 mg/kg; small and large intestine 0.16 mg/kg; blood 1.00 mg/L and urine 1.58 mg/L. Histopathological findings: Massive cerebral edema, focal necrosis of cerebellar tissue, pulmonary edema, multiple focal haemorrhages in myocardial tissue, diffuse myocardial lypomathosis and myofibrosis, multiple focal necrosis of hepatic tissue and chronic nephritis. Conclusion: Taking into account the circumstances, clinical picture, autopsy findings and toxicological results of post mortem materials our conclusion was that this was a unnatural death after oral ingestion of large amount of verapamil, a calcium channel blocker agent. doi:10.1016/j.toxlet.2008.06.083 Z61 2,5-Hexanedione (HD) treatment alters Calmodulin, Ca2+ /calmodulin-dependent protein kinase II, protein kinase C in rats nerve tissues Qing-Shan Wang ∗ , Ke-Qin Xie Institute of Toxicology, Shandong University, Jinan, China Recent studies have implicated the involvement of Ca2+ -dependent mechanisms, in particular Ca2+ /calmodulin (CaM)-dependent protein kinase II (CaMKII) in neurotoxin-induced neuropathy. However, it is unknown whether similar mechanisms occur in 2,5hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PR) of NF-L, pNF-M and pNF-H in cerebrum cortex (CC), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at dosage of 200 or 400 mg/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and positively correlated with gait abnormality. Expect for pNF-M in CC, the polymerization ratios of NFs were also elevated, which were consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might alter the NFs phosphorylation status and polymerization ratios to mediate the HD neurotoxicity. doi:10.1016/j.toxlet.2008.06.084

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Z62 Hepatic vitamin A reduction and CYP1A1 induction in rat offspring exposed to several dioxin-like compounds exclusively via lactation Emma Westerholm ∗ , Mattias Öberg, Helen Håkansson Karolinska Institutet, Stockholm, Sweden Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) are ubiquitous contaminants in human tissues and milk. The accumulated maternal exposure is mobilised during breast-feeding and lactational exposure constitutes the quantitatively largest intake in relation to body weight of dioxin-like compounds throughout life. Early postnatal development is known to be vulnerable to exposure of dioxin-like compounds. The study aim was to assess hepatic vitamin A (HVA) reduction and CYP1A1 induction in offspring exposed to dioxin-like compounds exclusively via lactation. Dams were given single oral doses of TCDD, PCDDs, PCDFs, and PCBs within 24 h of delivery. Offspring were exposed via lactation until weaning. Dose–response relationships were observed for both HVA reduction and CYP1A1 induction in offspring after TCDD exposure. Effects were established at similar dose levels for both HVA reduction and CYP1A1 induction, with the 5% effect levels being reached at 0.05 and 0.001 ␮g/kg BW respectively. About 70% of the offspring HVA stores were depleted at the highest TCDD dose. HVA reduction was also significant for CB 105, 126, and 169 with levels reduced about 50%. No significant HVA reductions were observed for the other congeners tested. Significant CYP1A1 induction was observed for all congeners tested, except CB77 previously reported to undergo fast metabolism, and reached a maximum of 30% that of TCDD at comparable doses. Both HVA reduction and CYP1A1 induction in offspring is markedly affected by TCDD exposure at similar dose levels. For the other congeners, different patterns are observed in ability to influence HVA reduction and CYP1A1 induction. doi:10.1016/j.toxlet.2008.06.085 Z63 Comparative study of specific inhibition of bcr-abl gene expression by chemically small interfering RNA and vector expression SiRNA Ali Zaree Mahmodabady ∗ , Ali Najafi, Mehdi Kamali, Hamid Javadi, Ali Khoshbaten Baqyatallah University, Tehran, Islamic Republic of Iran Small interfering RNAs (siRNAs) were designed and chemically synthesised to target the bcr-abl oncogene, which causes chronic myeloid leukemia (CML) and bcr-abl-positive acute lymphoblastic leukemia (ALL) and a different ShRNA sequence were designed for a3b2 and cloned in expression vector. Chemically synthesized anti-bcr-abl siRNAs were selected using reporter gene constructs and were found to reduce transiently bcr-abl mRNA up to 75% in bcr-abl-positive cell lines and in primary cells from CML patients