Search In this Thesis
   Search In this Thesis  
العنوان
Cell- free DNA (cf DNA) as a biomarker for acute myocardial infarction
المؤلف
Arafat, Eman Salah El-Deen El-Sayed. Arafat
هيئة الاعداد
باحث / ايمان صلاح الدين السيد عرفات
مشرف / نجلاء محمد غنايم
مشرف / ايمان عبد الفتاح بدر
مشرف / عبد الله مصطفي كمال
الموضوع
Biochemistry (cfDNA)-acute myocardial infarction-Biochemistry-
تاريخ النشر
2017
عدد الصفحات
165 p.:
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
14/8/2017
مكان الإجازة
جامعة المنوفية - كلية الطب - الكيمياء الحيوية الطبية
الفهرس
Only 14 pages are availabe for public view

from 189

from 189

Abstract

Summary
Acute myocardial infarction is one of the serious causes of acute chest pain so must be diagnosed effectively.
Myocardial infarction is defined by pathology as myocardial cell death due to prolonged ischemia. Cell death is categorized pathologically as coagulation and/or contraction band necrosis but can result to a lesser degree from apoptosis.
A diagnosis of myocardial infarction is made by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers.
cTnT and cTnI are now regarded as the most specific biochemical markers of myocardial injury. Studies have shown that cardiac troponins should replace CKMB as the diagnositic ‘gold standard’ for the diagnosis of myocardial injury.
Extracellular nucleic acids are found in human blood and cell culture medium as cell-free or bound to the cell-surface. The cell-free and cell-surface-bound extracellular nucleic acid are naturally forming complexes with proteins or membrane-bound particles in the form of mononucleosomes and/or oligonucleosomes and is released after the cleavage of easily accessible linkage sites of cellular DNA by endonucleases after cell death.
The major mechanism of cell free DNA release is significant necrosis and/or apoptosis of malignant cells and surrounding tissues. The debris from dying cells is normally phagocytosed and removed by macrophages. But this process is hampered in cancerous tissues.
Summary
132
Myocardial infarction (MI) is the end result of coronary artery disease and a condition associated with the apoptosis and death of cardiomyocytes. Cf-DNA is mainly released following programmed cell death or acute cellular inyury.
Cell free DNA concentration increase in the circulation of patients after AMI and may have prognostic potential.
The current study was carried out at the Medical Biochemistry and Cardiology Departments, Faculty of Medicine, Menoufia University. The aim of this study was conducted to identify the role of circulating cell-free DNA (cfDNA) as unique prognostic biomarker in patients with MI using real time PCR.
This study involved 80 subjects: 50 patients with acute myocardial infarction and 30 age and gender matched healthy subjects taken as control group. The patients were attendants of Intensive Care Unit, Menoufia university hospital during the period from May 2015 to May 2016.
The studied subjects were subjected to the following:
1- Full history taking and General and local cardiological examinations were made to every subjects.
2- ECG changes (elevation or depression of ST segment and pathological Q waves).
3- Laboratory investigations including:
 Cardiac biomarkers (troponin I & CK-MB)
 Kidney function tests (serum urea and creatinine).
 Liver function tests (AST& ALT).
 Lipid profile (cholesterol, trigleceride, LDL-c and HDL-c).
Summary
133
 Quantitative measurement of cfDNA in DNA extract by real time PCR technique
The results of the present study can be summarized as following:
 Hypertension (systolic & diastolic), history of ischemic heart disease and heart rate are significantly higher in AMI than the control group.
 EF, ESD and EDD are significantly different in AMI and control group
 Troponin, CKMB, triglyceride, total cholesterol and LDL-c are significantly higher in AMI than the control group.
 HDL-c is significantly decreased in AMI than the control group
 L1PA2-222, L1PA2-90 & L1PA2-222/L1PA2-90 ratio are significantly higher in AMI than the control group.
 There is positive correlation between cfDNA and hypertension, history of ischemic heart disease& site of infarction.
 L1PA2-90, L1PA2-222 and L1PA2-222/L1PA2-90 ratio are significantly decreased in 3rd day compared to 1st day
 The accuracy of cfDNA as a diagnostic marker of cell damage and apoptosis in myocardial infarction patients in 1st day was (66%), with sensitivity (54%), specificity (87%), positive predictive value (87%) and negative predictive value (53%) at cut off point of 0.610 ng /ml.
 The diagnostic accuracy of cfDNA as a diagnostic marker of cell damage and apoptosis in myocardial infarction patients in 3rd day was (54%), with sensitivity (36%) , specificity (84%), positive predictive value (78%) and negative predictive value (44%) at cut off point of 0.592ng /ml.
Summary
134
 The diagnostic accuracy of troponin I as a diagnostic marker of myocardial infarction in patients in 1st day was (100%), with sensitivity (100%) and specificity (100%) , positive predictive value (100%) and negative predictive value (100%) at cut off point of 101.5pg/ml.
 The diagnostic accuracy of troponin I as a diagnostic marker of myocardial infarction in patients in 3rd day was (94%), with sensitivity (90%) and specificity (100%), positive predictive value (100%) and negative predictive value (86%) at cut off point of 120 pg/ml.
 The diagnostic accuracy of CK-MB as a diagnostic marker of myocardial infarction in patients in 1st day was (99%), with sensitivity (98%) and specificity (100%), positive predictive value (100%) and negative predictive value (97%) at cut off point of 5.05ng/ml.
 The diagnostic accuracy of CK-MB as a diagnostic marker of myocardial infarction in patients in tthird day was (76%), with sensitivity (62%) and specificity (100%), positive predictive value (100%) and negative predictive value (61%) at cut off point of 4.7500ng/ml.