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العنوان
Study of the levels of advanced Glycation End Products in Sickle Cell Patients \
المؤلف
Sabrah, Aya Abo El-Macarem.
هيئة الاعداد
باحث / أية ابوالمكارم صبره
مشرف / ناهلة أحمد شلبى
مشرف / رشا عبد الرحمن الجمل
مشرف / محمود عادل كينى
تاريخ النشر
2019.
عدد الصفحات
137 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
أمراض الدم
تاريخ الإجازة
1/1/2019
مكان الإجازة
جامعة عين شمس - كلية الطب - الباثولوجيا الإكلينكية
الفهرس
Only 14 pages are availabe for public view

from 137

from 137

Abstract

Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to reduced quality of life and life expectancy. SCD is caused by a point mutation in a single gene, which results in a mutant β-globin protein (HbS), in which the sixth amino acid is changed from glutamic acid to valine. In the homozygous and some compound heterozygous states, deoxygenated HbS molecules form polymers, which damage the red cell membrane and increase its rigidity.
Clinical manifestations range from almost no symptoms to multiple, potentially fatal, events. Complications were divided according to three main categories including hematological, pain, and complications affecting major organs.
In addition to hemolytic anemia, some acute manifestations that usually occur include vaso-occlusive crisis, acute chest syndrome, priapism, sudden deafness, and acute anemia, commonly occurring in aplastic crisis and splenic sequestration conditions. Individuals with SCD are also more susceptible to stroke and serious bacterial infections
Oxidative stress is known to be a lifelong continuous process in SCD and was found to play a significant role in pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. The increased oxidative stress that associates SCD potentially enhances generation of advanced glycation end products (AGEs).
AGEs are well-established markers of oxidative stress, and were proved to be associated with disease severity in diabetes and inflammatory diseases.
Three main groups of AGEs have been described: (1) fluorescent crosslinking AGEs (e.g. pentosidine and crossline); (2) non-fluorescent crosslinking AGEs such as imidazolium dilysine cross-links resulting from reactions between glyoxal derivatives and lysine residues; (3) non- crosslinking AGEs (e.g N-ε- carboxymethyl lysine (CML)).
AGEs are formed by the non-enzymatic glycation of proteins, lipids or nucleic acids within the so-called “Maillard reaction”. They act either by modifying substrates, or by interacting with specific receptors.
This work aimed to study the relationship between AGE levels and the presence of SCD-related organ complications and their association with other clinical and laboratory data.
The study was conducted on 40 Egyptian SC patients who were recruited from patients attending Pediatric Hematology Clinic, Pediatric Hospital, Ain Shams University from September 2017 to September 2018.They were divided into 2 groups, group I (SCD patients without a history of vascular complications) and group II (SCD patients with a history of vascular complications) which was further subdivided into group IIa (SCD patients with sickle crises only) and group IIb (SCD patients with sickle crises± acute chest syndrome &/or stroke). All patients were selected based on the absence of concurrent diabetes mellitus, renal failure, auto-immune inflammatory diseases, malignancy or comorbidities at the time of sampling (inflammation, infection). In addition, 20 race-, sex- and age- matched healthy control subjects were also included. All patients and control group were subjected to full history taking, clinical examination, laboratory investigations and measurement of serum levels of AGE using ELISA (enzyme-linked immunosorbent assay) method employing the double-antibody sandwich technique.
The results revealed that the serum levels of AGEs including pentosidine and carboxymethyl-lysine were significantly higher in patients with sickle cell anemia compared to healthy controls.
According to our results, a statistically significant negative correlation was found with Hb level and statistically significant positive correlation with age, disease duration and ferritin level, but no significant correlation was found with BMI, TLC, HbS%,HbF%,LDH, total bilirubin and indirect bilirubin.
When we evaluated the relationship between AGE levels and development of vascular complications, we found a high significant difference in AGE levels between group I and group II where higher levels were related to history of vaso-occlusive complications. However when we studied the relationship between AGE levels and wider range of vascular complications (between group IIa and IIb), we found no significant difference between both groups. Because some parameters other than AGEs were significantly related to history of vaso-occlusive complications (e.g. ferritin, disease duration, HbS%), multiple regression analysis was employed to define the causal determinant of such complications and correct for any confounding factors. The results of multiple regression analysis have specified AGEs to be independently related to presence of history of vascular complications in SCD patients.
Moreover, using ROC curve, a numeric cutoff of
780 ng/ml for AGE was found efficient at detecting the development of vascular complications.