Gasoline exposure effect on professionals in El-Minya Governorate in Upper Egypt (2007–2008)

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S250 Abstracts / Toxicology Letters 189S (2009) S57–S273 G02 Effects of polyvalent antivenom on acute-phase response induced by Hottentota saulcyi and Mesobuthus eupeus scorpion venom in rats Mohammad Razi Jalali 1,, Reza Fatemi Tabatabaee 2 , Shahrokh Navidpour 3 , Hoda Mavalizadeh 4 1 Chamran University of Ahvaz, Clinical Pathology, Ahvaz, Islamic Republic of Iran, 2 Chamran University, Physiology, Ahvaz, Islamic Republic of Iran, 3 Razi Institute, Venomous Animals, Ahvaz, Islamic Republic of Iran, 4 Chamran University of Ahvaz, Ahvaz, Islamic Republic of Iran Scorpion venom can induce systemic alterations similar to those observed in acute-phase inflammatory response. In the present study, we report the changes of some indicators of inflamma- tion and acute-phase response in serum induced by Hottentota saulcyi and Mesobuthus eupeus. In addition the role of polyva- lent antivenom on these findings is also studied. For this study 100 male Wistar rats were divided to five equal groups randomly. Groups 1 and 2 received H. saulcyi venom (1.1mg/kg) with and without antivenom respectively. Groups 3 and 4 also injected with (1.4 mg/kg) of M. eupeus venom with and without antivenom respectively. Group 5 injected with normal saline as control group. Blood samples were taken at 0.5, 1, 3 and 6h after venom injec- tion. Results showed that both scorpions’ venom elicited quite similar responses in most assays in rats. Responses included increased C-reactive protein, increased plasma fibrinogen, systemic leukocytosis with a predominance of polymorphonuclear cells. Time-course analysis of these effects showed that responses are most pronounced on the first hours after envenomation. However, leukocytosis and changes in acute-phase protein concentrations can be observed up to 24 h after envenomation. Leukocyte parame- ters, CRP and plasma fibrinogen were reversed when SAV was given 20 min after envenoming. Keywords: Scorpion venom; Acute-phase response; CRP; Rat doi:10.1016/j.toxlet.2009.06.783 G03 Gasoline exposure effect on professionals in El-Minya Gover- norate in Upper Egypt (2007–2008) Khaled Ibrahim , Shaaban Ahmed Ministry of Justice, Medicolegal Department, Assuit, Egypt El-Minya City lies in the middle of Egypt between the Nile River and the Ibrahimiya Canal and considered as a market and financial center for its region. There were no previous studies on pollution caused by Gasoline exposure in El-Minya Governorate in Upper Egypt. So we tried in this study to concern on the effect of air pollution from automobile exhaust in El-Minya. Unleaded gaso- line was introduced in the greater area of El-Minya, 10% of the total sales of gasoline was unleaded. In this study, blood lead lev- els, liver function, kidney function, and hematological parameters were measured in groups of professionals exposed occupationally to polluted air with heavy traffic or gasoline fumes. According to the present study, we found a significant difference in blood lead levels in each of the exposed groups and an increase in hemoglobin level in all tested groups. On the other hand, creati- nine level shows decrease significant in all tested groups, increase SGOT and SGPT levels in gas station employees and taxi derivers and increase SGPT in bus drivers. On the other hand, there is no signifi- cant in SGOT level in bus driver. Perhaps the elevated transaminases resulted from exposure of gas station employees to hepatotoxic constituents of gasoline. Keywords: Gasoline; El-Minya Governorate; Gas station employees; Taxi drivers; Bus drivers doi:10.1016/j.toxlet.2009.06.784 G04 Determination and quantitation of clozapine and its metabo- lites in plasma by HPLC Emrah Dural, Görkem Mergen, Tülin Soylemezoglu Ankara University, Institute of Forensic Medicine, Ankara, Turkey Clozapine is classified structurally as a dibenzodiazepine deriva- tive. It is known as an atypical anti-psychotic agent with proven efficacy in the management of treatment-resistant schizophrenia and other psychotic disorders. Despite its high anti-psychotic and therapeutic potential, wider use of clozapine has been limited by the high risk of agranulocytosis which makes frequent hemato- logical monitoring and drug monitoring necessary. Clozapine is extensively metabolized in the liver by cytochrome P450 enzymes yielding several derivatives, mainly N-desmethylclozapine (nor- clozapine) and clozapine-N-oxide. This study intends to determine and quantify the levels of free clozapine and its metabolites in human plasma aiming for clinical contribution. For this purpose, a simple and reliable HPLC method for analyzing the concentra- tions of clozapine and its two major metabolites in human plasma was developed. An isocratic high-performance liquid chromatog- raphy method with ultraviolet detection at 220nm was utilized. Analytes are concentrated from plasma by liquid–liquid extraction with ethyl acetate, n-hexane and isoamylalcohol (80:15:5, v/v/v) which allows to obtain good extraction yields (>80%) for all ana- lytes. The analytes were separated on a C18 reversed-phase column using a mobile phase composed of acetonitrile, 62.4 mM phosphate buffer containing 0.3% triethylamine at pH 4.5. The relative stan- dard deviations for between and within-day assays were less than 4% for low concentrations of all analytes. The method was specific and sensitive with detection limits of 23.6 ng/mL, 19.3 ng/mL and 23.6 ng/mL for clozapine, N-desmethylclozapine and clozapine-N- oxide respectively. The procedure described is relatively simple, rapid and applicable to pharmacokinetic studies and routine ther- apeutic drug monitoring. Keywords: HPLC; Clozapine N-desmethylclozapine; Clozapine-N- oxide; Plasma doi:10.1016/j.toxlet.2009.06.785 G05 Quetiapine treatment in resistant depression: A prospective study Etienne Hafnia 1,, Daniela Ionescu 1,2 1 Municipal Hospital, Psychiatry, Tunis, Romania, 2 University, Toxicology, Timisoara, Romania Aim: Rationale therapy of resistant depression (TRD) is an impor- tant clinical problem, and represents a considerable challenge to

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250 Abstracts / Toxicology L

02ffects of polyvalent antivenom on acute-phase response

nduced by Hottentota saulcyi and Mesobuthus eupeus scorpionenom in rats

ohammad Razi Jalali 1,∗, Reza Fatemi Tabatabaee 2, Shahrokhavidpour 3, Hoda Mavalizadeh 4

Chamran University of Ahvaz, Clinical Pathology, Ahvaz, Islamicepublic of Iran, 2 Chamran University, Physiology, Ahvaz, Islamicepublic of Iran, 3 Razi Institute, Venomous Animals, Ahvaz, Islamicepublic of Iran, 4 Chamran University of Ahvaz, Ahvaz, Islamicepublic of Iran

corpion venom can induce systemic alterations similar to thosebserved in acute-phase inflammatory response. In the presenttudy, we report the changes of some indicators of inflamma-ion and acute-phase response in serum induced by Hottentotaaulcyi and Mesobuthus eupeus. In addition the role of polyva-ent antivenom on these findings is also studied. For this study00 male Wistar rats were divided to five equal groups randomly.roups 1 and 2 received H. saulcyi venom (1.1 mg/kg) with andithout antivenom respectively. Groups 3 and 4 also injectedith (1.4 mg/kg) of M. eupeus venom with and without antivenom

espectively. Group 5 injected with normal saline as control group.lood samples were taken at 0.5, 1, 3 and 6 h after venom injec-ion. Results showed that both scorpions’ venom elicited quiteimilar responses in most assays in rats. Responses includedncreased C-reactive protein, increased plasma fibrinogen, systemiceukocytosis with a predominance of polymorphonuclear cells.ime-course analysis of these effects showed that responses areost pronounced on the first hours after envenomation. However,

eukocytosis and changes in acute-phase protein concentrationsan be observed up to 24 h after envenomation. Leukocyte parame-ers, CRP and plasma fibrinogen were reversed when SAV was given0 min after envenoming.

eywords: Scorpion venom; Acute-phase response; CRP; Rat

oi:10.1016/j.toxlet.2009.06.783

03asoline exposure effect on professionals in El-Minya Gover-orate in Upper Egypt (2007–2008)

haled Ibrahim ∗, Shaaban Ahmed

Ministry of Justice, Medicolegal Department, Assuit, Egypt

l-Minya City lies in the middle of Egypt between the Nile Rivernd the Ibrahimiya Canal and considered as a market and financialenter for its region. There were no previous studies on pollutionaused by Gasoline exposure in El-Minya Governorate in Uppergypt. So we tried in this study to concern on the effect of airollution from automobile exhaust in El-Minya. Unleaded gaso-

ine was introduced in the greater area of El-Minya, 10% of theotal sales of gasoline was unleaded. In this study, blood lead lev-ls, liver function, kidney function, and hematological parametersere measured in groups of professionals exposed occupationally

o polluted air with heavy traffic or gasoline fumes.

According to the present study, we found a significant difference

n blood lead levels in each of the exposed groups and an increasen hemoglobin level in all tested groups. On the other hand, creati-ine level shows decrease significant in all tested groups, increaseGOT and SGPT levels in gas station employees and taxi derivers and

T

At

189S (2009) S57–S273

ncrease SGPT in bus drivers. On the other hand, there is no signifi-ant in SGOT level in bus driver. Perhaps the elevated transaminasesesulted from exposure of gas station employees to hepatotoxiconstituents of gasoline.

eywords: Gasoline; El-Minya Governorate; Gas station employees;axi drivers; Bus drivers

oi:10.1016/j.toxlet.2009.06.784

04etermination and quantitation of clozapine and its metabo-

ites in plasma by HPLC

mrah Dural, Görkem Mergen, Tülin Soylemezoglu ∗

Ankara University, Institute of Forensic Medicine, Ankara, Turkey

lozapine is classified structurally as a dibenzodiazepine deriva-ive. It is known as an atypical anti-psychotic agent with provenfficacy in the management of treatment-resistant schizophreniand other psychotic disorders. Despite its high anti-psychotic andherapeutic potential, wider use of clozapine has been limited byhe high risk of agranulocytosis which makes frequent hemato-ogical monitoring and drug monitoring necessary. Clozapine isxtensively metabolized in the liver by cytochrome P450 enzymesielding several derivatives, mainly N-desmethylclozapine (nor-lozapine) and clozapine-N-oxide. This study intends to determinend quantify the levels of free clozapine and its metabolites inuman plasma aiming for clinical contribution. For this purpose,simple and reliable HPLC method for analyzing the concentra-

ions of clozapine and its two major metabolites in human plasmaas developed. An isocratic high-performance liquid chromatog-

aphy method with ultraviolet detection at 220 nm was utilized.nalytes are concentrated from plasma by liquid–liquid extractionith ethyl acetate, n-hexane and isoamylalcohol (80:15:5, v/v/v)hich allows to obtain good extraction yields (>80%) for all ana-

ytes. The analytes were separated on a C18 reversed-phase columnsing a mobile phase composed of acetonitrile, 62.4 mM phosphateuffer containing 0.3% triethylamine at pH 4.5. The relative stan-ard deviations for between and within-day assays were less than% for low concentrations of all analytes. The method was specificnd sensitive with detection limits of 23.6 ng/mL, 19.3 ng/mL and3.6 ng/mL for clozapine, N-desmethylclozapine and clozapine-N-xide respectively. The procedure described is relatively simple,apid and applicable to pharmacokinetic studies and routine ther-peutic drug monitoring.

eywords: HPLC; Clozapine N-desmethylclozapine; Clozapine-N-xide; Plasma

oi:10.1016/j.toxlet.2009.06.785

05uetiapine treatment in resistant depression: A prospective

tudy

tienne Hafnia 1,∗, Daniela Ionescu 1,2

Municipal Hospital, Psychiatry, Tunis, Romania, 2 University,

oxicology, Timisoara, Romania

im: Rationale therapy of resistant depression (TRD) is an impor-ant clinical problem, and represents a considerable challenge to