effect of toxicokinetics of thiono-organophosphorus pesticides on their detection in postmortem...
TRANSCRIPT
etters
wpt(wEts
wpstnucs
d
PCc
LMG
1
BA4
(edwtedouawlsoaPCutmsam
d
Abstracts / Toxicology L
as normal. 15 min later, the patient complained of retrosternalain with mild dyspnea. A second ECG showed a three millime-ers ST elevation in I and II. A NaHCO3 infusion was established150 mEq in 30 min + continuing infusion) until a plasma pH of 7.50as reached, with a rapid improvement of clinical condition and
CG normalization 90 min later. The patient was subjected to gas-ric lavage and plasma alkalosis was maintained for 12 h withoutigns of cardio-or neurotoxicity during clinical observation.
Results of the study: Common side effects of quetiapine includeeight gain, constipation, headache and dry mouth. Six to sevenercent of patients may experience tachycardia. Less commonide effects (less than 1% of patients) include abnormal liverests, dizziness, upset stomach, substantial weight gain, a stuffyose, akathisia and increased paranoia. ECG abnormalities are veryncommon. In this case we also want to point out how thesehanges have completely normalized without the use of cardiac-pecific drugs, but only with sodium bicarbonate infusion.
oi:10.1016/j.toxlet.2011.05.312
1079hronic exposure to inorganic arsenic in children influencesoncentration of nitric oxide metabolites in plasma and urine
.M. Del Razo 1,∗, E. Hernandez-Castellanos 1, H. Vargas-Robles 2,.A. Sanchez Guerra 1, L.C. Sanchez-Pena 1, L. Arreola-Mendoza 3,. Aguilar-Madrid 4, C. Osorio-Yanez 1
Toxicology, Cinvestav, Distrito Federal, Mexico, 2 Moleculariomedicine, Cinvestav-IPN, Distrito Federal, Mexico, 3 Biosciencesnd Engineering, CIIEMAD-IPN, Distrito Federal, Mexico,Occupational Health Research, IMSS, Distrito Federal, Mexico
Millions of people worldwide are exposed to inorganic arseniciAs), in drinking water. iAs exposure has been associated with pres-nce of atherosclerosis in humans. Atherosclerosis is a multistageisease that can initiate at childhood and stays silent until adult age,hen the clinical manifestations occur. There is a growing interest
o prevent cardiovascular disease early in the course of the diseaseven at a pediatric stage. Nitric Oxide (NO) is the key endothelium-erived relaxing factor that plays a pivotal role in the maintenancef vascular tone. Measurement of its circulatory stable end prod-cts, nitrite/nitrate (NOx), metabolites of NO have been widely useds an index of endothelial NO synthase activity. The aim of this studyas to explore in children the potential association between the
evels of NOx and iAs exposure evaluated in urine. A cross-sectionaltudy was conducted with 193 children (3–14 years old), residentsf endemic area in Mexico. iAs and its metabolites in urine werenalyzed by hydride generation-atomic absorption spectroscopy.lasma and urine NOx levels were evaluated by Griess methods.oncentrations of sum of iAs and its metabolites (MAs and DMAs) inrine were 5.7–369 �g/L (mean = 58.9 �g/L). While mean concen-rations of NOx in urine were 114.25 (24.94–474.27) �mol/L, and
ean NOx in plasma were 5.23 (1.67–16.43) �mol/L. Our resultshow a significant correlation between levels of NOx and urinaryrsenic concentration, which imply that NOx could be used for
onitoring effects associated to iAs exposure.Funded by Conacyt, Mexico.oi:10.1016/j.toxlet.2011.05.313
205S (2011) S60–S179 S85
P1080Validation of a fully automated toxicological LC–MS screeningfor plasma sample analysis using online extraction withturbulent flow chromatography
B. Duretz 1,∗, M. Manchon 2, J. Guitton 2, S. Cohen 2, C. Moreau 2
1 ThermoFisher, Courtaboeuf, France, 2 Laboratoire De Biochimie,Hopital Lyon Sud, Pierre Benite, France
Purpose: LC/MS is a powerful tool widely used for targeted drugscreening. However, the quality of the results is largely affectedby sample preparation methods. Offline solid phase extraction(SPE) and liquid–liquid extraction (LLE) are widely used but areoften time consuming and expensive. Here we will present anon-line sample preparation extraction using TurboFlow technol-ogy for the screening of more than 400 acidic, neutral and basicdrugs in plasma using LC/MSMS. Methods: Two TurboFlow columns(Cyclone, C18XL) were connected in series and used for sam-ple extraction. 100 �l of plasma samples were diluted in 100 �lof acetonitrile. The mixture was then centrifuged and 50 �l ofsupernatant was injected into the system. The LC separation wasperformed using an Hypersil GOLD PFP column. MS2 spectra werethen acquired on a LXQ ion trap mass spectrometer (Thermo Sci-entific) and library searching was performed automatically usingToxID software. Results: The method has first been developed inZurich Hospital and transferred into the laboratory for plasmaanalysis. A validation of the method was performed by check-ing the following parameters: matrix effect, extraction efficiencyand reproducibility. A minor matrix effect (suppression < 20%) wasobserved for most of the compounds. 65% of the substances showeda recovery higher than 75% and precision values were lower than15% for more than 80% of the compounds. Conclusion: The methodhas been fully validated and is now running routinely. The analysisruntime is 30 min and includes sample preparation, analysis andprocessing.
doi:10.1016/j.toxlet.2011.05.314
P1081Effect of toxicokinetics of thiono-organophosphoruspesticides on their detection in postmortem human specimens
F.A. Elwan
Forensic Chemistry Laboratories, Forensic Medicine ScienceAuthority, Cairo, Egypt
Introduction: Thiono-organophosphorus (thiono-OP) pesticidesare much weaker inhibitors or do not inhibit acetylcholinesterase(AChE) at all, need to be biotransformed in the body to be effective.All thiono-OP pesticides, that are those containing a P S bond, arenot active inhibitors of AChE, but require activation by oxidation.The intrinsically reactive chemical nature of thiono-OP pesticidesmeans that any dose entering the body is immediately liable toa number of biotransformations and reactions with tissue con-stituents. Aim: The study tried to Pursuance the occurrence ofthiono-OP pesticides and detects their biotransformation in bothfluids and tissues of deceased, taking into account their toxicokinet-ics in the body, in addition to, detecting the residual of thiono-OP inexhumed viscera. Methods: Thiono-OP pesticides and their metabo-
lites were extracted from: fluids, tissues and exhumed viscera usingliquid/liquid extraction. Thiono-OP pesticides are converted chem-ically by suitable oxidizing agents to their oxons and differentoxidative products of branched groups attached to the main groupS etters
oppipatttp
d
PTl
W
urfci(giMcaiPiL7itmttsmticAi
d
86 Abstracts / Toxicology L
f thiono-OP. All these compounds and the parents of thiono-OPesticides are hydrolyzed in different pH to produce the hydrolyticroducts of them. Results: The extracted metabolites from both flu-
ds and tissues are significantly different, and the biotransformedroducts are only the detectable in all specimens. Conclusion: Thectivation of thiono-OP pesticides may be occurring in fluids andissues other than the liver. Consequently, the extracted chemicallyransformed products of the tested thiono-OP pesticides and theiroxicokinetics are very important factors in detection the up takenesticides in postmortem specimens.
oi:10.1016/j.toxlet.2011.05.315
1082he relationship between agouti related-protein (AgRP) andeptin in smoking cannabis
.M. Fathy
Chemistry Lab., Forensic Medicine Authority, Cairo, Egypt
Aim: Try to find out, the food intake mechanism, of subjectsnder investigation, who are smoking cannabis, by studying theelationship between the most two popular hormones controllingood intake (leptin hormone, and agouti related protein hormone),omparing with healthy subjects. Methods: Group II (GII): consist-ng of ten 10 males, with positive 9-carboxy-tetrahydrocanabinolTHC) was detected in their urine by qualitative analysis usingas chromatography–mass spectrometry (Agilent 6080N – cap-llary column 30 m to 1 �m diameter) collected from Forensic
edicine Institute Chemistry Lab., Cairo, Egypt. Group I (GI):onsisting of ten 10 control healthy males as volunteers with neg-tive 9-carboxy-tetrahydrocanabinol (THC). Age and body massndex (BMI) were matched, diabetic subjects were excluded.lasma leptin concentration was measured by quantitative radiommunoassay (RIA) using a kit supplied from diagnostic systemsaboratories (DSL) Inc. (445 Medical Center BLVB, Websteer, TX7598, USA). The method depend on a non-competitive assay
n which the analyte to be measured is “sandwiched” betweenwo antibodies. Human plasma AgRP hormone was quantitatively
easured by using a kit supplied from Quantikine R&D Sys-ems Inc. (614 McKinley Palace, Minneapolis, MN 55413, USA),his assay employs the quantitative sandwich enzyme immunoas-ay technique. Results: In group I (GI), there was a decrease inean plasma leptin concentrations ± SD 6.39 ± 1.93 ng/ml, than
hat found, in group II (GII) 4.49 ± 1.40 ng/ml, but it is statisticallynsignificant. There was an elevation, in mean plasma AgRP con-entrations 27.77 ± 2.17 pg/ml in GII, comparing with mean plasma
gRP concentrations 25.84 ± 1.93 pg/ml, in GI but it is statisticallynsignificant.
oi:10.1016/j.toxlet.2011.05.316
205S (2011) S60–S179
P1083Methylmercury exposure and abnormal neurological findingsin Amazonian riparians from Madeira river, Portovelho (RO),Brazil
M.F. Fonseca 1,∗, S.S. Hacon 2, L.S.V. Jacobson 3, J.G. Dorea 4,D. Mourao 2, W.R. Bastos 5
1 Servico De Anestesiologia, Instituto Fernandes Figueira-Fiocruz, RioDe Janeiro, Brazil, 2 ENSP-FIOCRUZ, Rio de Janeiro, Brazil, 3 UFF, Riode Janeiro, Brazil, 4 UnB, Brasilia, Brazil, 5 UNIR, Porto Velho, Brazil
Purpose: Amazonian riparian communities are usually exposedto high levels of methylmercury (MeHg) because of heavy fishintake. We have been surveying Amazonian riparians looking forneurological findings associated to fish-MeHg exposure. Methods:A qualified physician carried out a clinical examination (includ-ing neurological evaluation) of 714 individuals (ages 1–93 years);they were categorized as normal or abnormal for each neurolgo-ical test. Besides, individual fish-MeHg exposures were assayedby hair chemical analysis, in which total hair-Hg concentration(HHg) was determined by atomic absorption spectrometry (FIMS-400® Perkin-Elmer). Results: HHg (�g g−1) for normal and abnormalindividuals averaged, respectively, 8.82 and 5.70 (p = 0.092) formotor coordination (rapid alternative); 8.36 and 11.15 (p = 0.494)for left, and 8.36 and 9.78 (p = 0.744) for right manual finger move-ments; 8.43 and 7.88 (p = 0.763) for aquiles (sacral S1–S2), 8.36and 8.54 (p = 0.912) for patellar (lumbar L2–L4), and 8.19 and 9.49(p = 0.469) for finger flexors (cervical/thoracic C6–T1) deep tendonreflex. Postural control and equilibrium (Romberg sign); vibratorysensitivity (utilizing a 128 Hz tuning fork); tactile discriminationbetween two points (normal if below 0.5 mm); walking; intentionalor at rest occurrences of tremor; abnormal eye movements (asym-metry/nistagmus); muscular strength; stereognosis; joint positionsense (hallux) or clinical evaluation of speech and auditory capac-ity were normal in practically all. In general terms, HHg was notstatistically associated to any abnormality. Nevertheless, our teamkeeps focus on individuals whose values were above threshold forneurological effects; they must be watchfully examined.
This study has been approved by a Human Research Ethics Com-mittee.
doi:10.1016/j.toxlet.2011.05.317
P1084The role of urinary rapid tests in acute poisoning in children
V.G.D. Nitescu ∗, V. Crisan, A. Ulmeanu, T. Pasatoiu, M. Barbu,C.E. Ulmeanu
Clinical Toxicology and Intensive Care, Pediatric Poisoning CentreChildren’s Hospital Grigore Alexandrescu, Bucharest, Romania
Purpose: To analyze the value of the urinary rapid test inacute poisoning diagnosis. Methods: We performed a retrospec-tive study of urinary tests performed in children admitted in aClinical Toxicology Unit with suspected poisoning, suspected over-doses of drugs of abuse or ethno botanical substances, alcoholpoisoning, benzodiazepines, barbiturates and tricyclic antidepres-sants poisoning .We used rapid urinary tests of which workingprinciples are high specific immunochemical antigen–antibody
reactions. The tests simultaneously identify: barbiturates, benzo-diazepines, cocaine, cannabinoids, methamphetamines, opiates,tricyclic antidepressants and phencyclidine. The results wereverified by gas chromatography (GC) and gas chromatography