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Ehab Shaaban Mohamed EL-Osely M.B., B

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Ehab Shaaban Mohamed EL-Osely M.B., B INFLUENCE OF SOME PESTICIDES ON HUMORAL AND CELLULAR IMMUNITY OF EXPOSED WORKERS IN PESTICIDES INDUSTRIES By Ehab Shaaban Mohamed EL-Osely M.B., B. Ch. Faculty of Medicine, Ain Shams university1994 Master in radiodiagnosis, Faculty of Medicine, Ain Shams university1998 A Thesis Submitted in Partial Fulfillment of The Requirement for the Doctor of Philosophy Degree In Environmental Science Department of Medical Science Institute of Environmental Studies & Research Ain Shams University Under The Supervision of: 1- Prof. Dr. Mostafa Mohamed EL Rasad Prof. of Biochemistry Faculty of Medicine, Ain Shams University 2- Dr. Mahmoud Lotfy Sakr Associate Prof. of Forensic Medicine and Toxicology Faculty of Medicine, Ain Shams University 3- Prof. Dr. Zidan Hindy Abdel Hamid Zidan Prof. of Pesticides Chemistry and Toxicology Faculty of Agriculture, Ain Shams University 4- Dr. Amany Mohamed Ezz El-Din Associate Prof. in Radiation Health Research Department National Center for Radiation Research and Technology 5- Dr. Inas Mohamed Fawzy Gaballah Associate Prof. of Industrial medicine Faculty of Medicine, Cairo University 2010 - 1 - Acknowledgement First and foremost thanks to ALLAH to whom I relate any success in achieving any work in my life. I would like to express my deepest appreciation and gratitude to the sole of Prof. Dr. Mostafa Mohamed EL- Rasad, Professor of Biochemistry, Faculty of Medicine Ain Shams University, for suggesting and planning this study. No words can express my deepest thanks to him. My sincere appreciation and special thanks to assistant professor Dr. Mahmoud Lotfy Sakr, assistant professor of clinical toxicology, Faculty of Medicine Ain Shams University, for his overwhelming kindness and encouragement, his keen supervision, continuous guidance, experienced advice. My sincere thanks to Prof. Dr. Zidan Hindy Abdel- Hamid Zidan, professor of pestecides chemistry and toxicology, Faculty of Agriculture, Ain Shams University, for his great effort, constructive advice and valuable guidance. I am also very grateful to Prof. Dr. Amany Mohamed Ezz El-Din, professor in Radiation health research department, National center for Radiation research and technology, Atomic Energy Authority for her expert guidance, kind scientific supervision and precious time she offered me. Special thanks to Prof. Dr. Inas Mohamed Fawzy Gaballah, professor of Industrial Medicine, Faculty of Medicine, Cairo University, for her co-operation. - 2 - My thanks to Dr. Amr Ibrahim Saied, lecturer in Radiation health research department, National center for Radiation research and technology, Atomic Energy Authority for his support. Last but not least I would like to thank my wife for her extreme patience and endless love. - 3 - AAbbssttrraacctt - 4 - Abstract Pesticide poisoning is a major public health problem in developing countries. In most of these countries organophosphate pesticides constitute the most widely used pesticides. The main toxicity of OPs is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect the immune response, including effects on cellular and humoral immunity. Our study examined the effect of organophosphorus compounds on humoral and cellular immunity of exposed workers in pesticides industries. The study was conducted into 40 subjects. They were 2 groups; 20 exposed workers from Gharbeia and Kafr Elsheikh at 2008 and 2009 and 20 unexposed individuals as a control group at the same period of time. We examined some immune parameters; pseudocholinesterase, WBCs count, CD4%, CD8%, CD4/CD8, CD56%, Interleukin 2, IgG and IgM. Also we take history and clinical examination for them. We reported a highly significant decrease in pseudo cholinesterase level among the exposed group in comparison to the control group, highly significant increase in percentage of CD8 in the exposed group in comparison to control group, highly significant decrease in CD4 / CD8 ratio in the exposed group in comparison to control group, highly significant decrease in percentage of CD56 in the exposed group in comparison to control group and a highly significant increase in IgG level in the exposed group in comparison to control group. On the other hand, we reported no significant change in white blood cells count between the exposed and control groups, no significant change in percentage of CD4 among the exposed and control group, no significant - 5 - change in Interleukin 2 level among the exposed and control group and no significant change in IgM level among the exposed and control group. We concluded that pesticides extensively affect the humoral and cellular immune system of occupationally exposed workers. - 6 - Contents Title Page Abstract --------------------------------------------------- Introduction and aim of the work-------------------- XI Aim of the work ------------------------------------------ XIII Review of literature: Pesticides--------------------------------------------- 1 Classification of pesticides------------------------- 1 Pharmacokinetics------------------------------------ 10 Toxicity----------------------------------------------- 15 Immunity--------------------------------------------- 34 Innate immunity-------------------------------------- 34 Cell mediated immune response-------------------- 41 Humoral immune response-------------------------- 46 Subjects and methodology------------------------- 58 Results------------------------------------------------ 69 - 7 - Discussion-------------------------------------------- 94 Summary--------------------------------------------- 103 Conclusion------------------------------------------- 107 Recommendations---------------------------------- 109 References------------------------------------------- 111 Arabic summary------------------------------------ - 8 - List of Tables Table Page Table (1): Classification of pesticides combined functional and chemical classification by Gunn and Stevens (1990) ………………...1 Table (2): The classification of organic phosphorus agents by groups. Leaving groups and examples of each group are included ……..7 Table (3): Age distribution among the studied groups.........................................................70 Table (4): Student t test showing Pseudo cholinesterase level among the studied groups …….........................................................71 Table (5): Student t test showing white blood cells count among the studied groups ……...………73 Table (6): Student t test showing CD4 % among the studied groups …….………….………...75 Table (7): Student t test showing CD8 % among the studied groups …...………………………77 - 9 - Table (8): Student t test showing CD4/CD8 ratio among the studied groups ……………………….79 Table (9): Student t test showing CD56 % among the studied groups …………………………..81 Table (10): Student t test showing Interleukin 2 level among the studied groups ………………83 Table (11): Student t test showing IgG level among the studied groups …………………………85 Table (12): Student t test showing IgM level among the studied groups …………………………87 Table (13): Biochemical parameters in blood samples collected from normal individuals at different locations in Gharbeia and Kafr Elsheikh ………………………………..89 Table (14): Mean biochemical parameters in blood samples collected from normal individuals at different locations in Gharbeia and Kafr Elsheikh ………………………………..91 Table (15): Biochemical parameters in blood samples collected from continues exposed individuals at different locations in Gharbeia and Kafr Elsheikh ………………………92 - 10 - List of Figures Figure Page Figure (1): Mechanism of acetylcholine binding and organophosphate binding to the acetylcholinesterase ........................................ 14 Figure (2): Structure of some commonly used organophosphorous pesticides ......................... 17 Figure (3): Pathophysiology of cholinergic syndrome as it affects the autonomic and somatic nervous system ................................................ 18 Figure (4): Histogram showing comparison between mean pseudo cholinesterase levels in exposed and control group.. ............................. 72 Figure (5): Histogram showing comparison between mean White blood cells count in exposed and control group............................................. 74 Figure (6): Histogram showing comparison between mean CD4 % in exposed and control group. .............................................................. 76 - 11 - Figure (7): Histogram showing comparison between mean CD8 % in exposed and control group.. ............................................................. 78 Figure (8): Histogram showing comparison between mean CD4/CD8 ratios in exposed and control group.. ................................................. 80 Figure (9): Histogram showing comparison between mean CD56 % in exposed and control group.. ............................................................. 82 Figure (10): Histogram showing comparison between mean Interleukin 2 level in exposed and control group ................................................... 84 Figure (11): Histogram showing comparison between mean IgG level in exposed and control group ............................................................... 86 Figure (12): Histogram showing comparison between mean IgM level in exposed and control group . ............................................................. 88 - 12 - List of Abbreviations Ab Antibody Abos Abosasa (Gharbeia) AchE Acetyl cholinesterase enzyme ACTH Adrenocorticotropin ADCC Antibody-dependent cell mediated cytotoxicity Ag antigen ALT Alanine or aniline
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