International Conference on Toxicogenomics and Drug Monitoring August 25-27, 2015 Valencia, Spain

Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in neurotoxicology and neurodevelopmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012 he was Associated Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2012 he got a position as Assistant Professor of Toxicology at the Complutense University of Madrid.

4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. Thereis a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects that have been reported. Moreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal pathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death induced by 4-aminipyridine. To provide that 4-AP is able to induce cell death in vivo and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic range of doses, was conducted in rat livers. The caspases 3/7 activation, LDH release a real-time PCR array analysis was developed. The caspases 3/7 were activated and the lactate dehydrogenase (LDH) release was increased at all doses confirming that 4-AP induce cell death in rat liver in vivo. Moreover, this data suggest that both necrotic and apoptotic process take place at the same time. Furthermore, the the real-time PCR array on liver tissue expressed a gene expression profile of necrotic and apoptotic induced cell death which support our biochemical results. The present work shows for the first time in vivo cell death on liver induced by 4-AP and the biochemical and the gene expression profile shows that the cell death is mediated by necrotic and apoptotic pathways.

Eman I. Draz has PhD of clinical toxicology from Faculty of medicine, Tanta University Egypt on 2004. Has deploma in Total quality management, Amrican University Collage, Egypt. Former manager of poison control center, Tanta University hospital , Egypy. Manager of general service center, Faculty of medicine, Tant University. Has published 12 papers in reputed journals and has been serving as reviewer in international journals

Cannabis is one of the most widely cultivated, trafficked and abused illicit drugs all over the world. Recent studies concluded that smoked cannabis (Hashish and Bango) has the highest prevalence among substances induced disorder used in Egypt. Common Risk factors of cardiac disease include obesity, weight, sedentary lifestyle , age, metabolic factors such as elevated cholesterol levels, and tobacco smoking. There is controversy in studies concerning cannabis related cardiovascular disease. Most of these studies depend on patients history of cannabis usage which may be false. Aim of this work is to study the possible association of cannabis consumption and the development of the myocardial injury in low risk males and to specify the cardiac pathological changes developed in cannabis exposed patients. This is a cross sectional study that was carried out on 138 male patients, aged 40 years or less, with acute myocardial infarction admitted to the intensive care unit of Cardiology care unit , Tanta University hospital during the period from August 2014 to January 2015. Urine samples were submitted for toxicological analysis of drugs related disorders using a homogenous enzyme immunoassay technique. Cannabis positive patients were approximately 27% of all studied patients. Other risk factors of cardiac disease including hypertension, diabetes and dyslipidemia were absent in cannabis positive patients. In relation to cannabis levels in urine, there were significant changes in ECG changes including STEMI and NSTEMI , Coronary angiography including one, two or three vessels occlusion and Echo- cardiography as regards good, fair cardiac output and diastolicrndysfunction . The study concluded that cannabis could be a potential riskrnfactors for development of cardiac ischemia. Further studies to relaterncannabis body levels with cardiovascular diseases are recommended.rnDrugs and substance screening using a conventional toxicologicalrnlaboratory method is crucial to Relate the development of ischemic heart disease and exposure to cannabis.

Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in neurotoxicology and neurodevelopmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012 he was Associated Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2012 he got a position as Assistant Professor of Toxicology at the Complutense University of Madrid.

Amitraz is a formamidine pesticide widely used as an insecticide and acaricide. Many amitraz poisoning cases in humans have been reported worldwide and still being described up today, which is a cause of concern for health authorities. The amitraz has been reported to be a neurotoxic compound inducing convulsion among other effects. The alpha-2 adrenergic agonist and/or local anesthetic-like properties of these compounds have been reported as likely responsible for the seizure enhancing effects. Moreover, other mechanism could be implicated. In this regard Amitraz it is an inhibitor of H1 receptor and the inhibition of histamine H1 receptor has also been implicated in seizure induction. Amitraz seizure induction could be mediated by some of the mechanism commented through a dysfunctions on GABAergic systems. To confirm if amitraz disrupt GABAergic transmission by local anesthetic-like action, inhibition of H1 receptor and activation of alpha-2 receptor, we evaluated, in primary hippocampal neurons, the effect of amitraz (0.01µM 100µM) with or without idazoxan (1 µM) and/or n-methylhistaprodifen (30µM) and lidocaine (20mM) co-treatment on 4-aminobutyrate aminotransferase (GABAT), Glutamate Decarboxylase 65 (GAD65), succinate-semialdehyde dehydrogenase (SSADH) gene expression and GABA levels after 24h treatment. We observed that amitraz alter GABAergic transmission disrupting the expression of GAD 65 and thus GABA levels. These effects were mediated partially by H1 and alpha-2 receptors suggesting that other mechanism could be implicated. These data help to explain the way amitraz induce seizures and a way to protect against this effect in the cause of poisoning.