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العنوان
Role of P-Glycoprotein Efflux Capacity on Antiepileptic Drugs Efficacy /
المؤلف
Hassan, Rhab Basem Mohamed .
هيئة الاعداد
باحث / رحاب باسم محمد حسن
مشرف / فادي محمد الجندي
مشرف / حسن سعيد عثمان بدر
مشرف / سامح عبد الله عبد النبي
مشرف / محمد أحمد حلوة
الموضوع
Epilepsy in children. Epilepsy therapy Child.
تاريخ النشر
2023.
عدد الصفحات
120 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
20/5/2023
مكان الإجازة
جامعة المنوفية - كلية الطب - طب الاطفال
الفهرس
Only 14 pages are availabe for public view

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from 134

Abstract

Epilepsy is one of the most common neurological diseases and affects people of all ages, races, social classes, and geographical locations.
The prevalence of epilepsy is 6.4 cases per 1000 persons, and the annual incidence is 67.8/per 100,000 person-years.
Antiepileptic drugs are the cornerstone of epilepsy treatment. The aim of treatment is to get rid of seizures, no side effects and a good quality of life for patient.
Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses.
In recent years, one of the potential mechanisms gaining the interest of researchers is the over-expression of P- glycoprotein (P-gp, also known as ABCB1 or MDR1) in endothelial cells of the blood-brain barrier (BBB) in epilepsy patients. P-gp plays a central role in drug absorption and distribution in many organisms. Some studies also indicate that several AEDs are substrates or inhibitors of P-gp, implying that P-gp may play an important role in drug resistance in refractory epilepsy.
Our study aimed to measure the serum level of P-gp as a possible indicator of tissue p-gp overexpression in patients with (DRE) and to assess the role of P-glycoprotein efflux capacity on antiepileptic drugs efficacy and evaluation of its role in drug resistant cases.
The current research was case-control study included 90 children randomly selected from pediatric neurology outpatient clinic, and
Summary
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neurology unit in pediatric department at Menoufia University Hospital during the period from December 2018 to November 2021. The study was conducted after approval of the institutional review board of the Menoufia Faculty of Medicine. Informed written consent was taken from the children’s care-givers. Children were divided into three groups. group A included 45 epileptic children receiving antiepileptic drugs with medically controlled seizure (Drug- responsive). group B included 30 epileptic children receiving antiepileptic drugs not medically controlled (Drug- resistant) or (refractory). group C included 15 clinically healthy children as a control group.
All patients with abnormal radiological brain imaging, chronic liver or kidney diseases; neurological brain insult, neurocutaneous syndromes, or neurodegenerative brain diseases were excluded from the study.
All included patients were administered antiepileptic drugs within one year prior to enrollment. Pgp serum levels were measured for all groups at the beginning of the study using human permeability glycoprotein (P-gp) by IO Test Conjugated Antibody known CD243-PE Kits using facscaliba flow cytometry.
According to P-gp Marker in studied groups; we found that P-gp serum levels in patients with DRE were significantly elevated compared to patients with medically controlled epilepsy (responsive group) with a P value (0.04); and non-epileptic children ( control group) with a P value (0.01) regarding Pgp expression.
Regarding validity of PGP expression for detection of refractory state we found that the cutoff point of Pgp is 0.625, sensitivity 73.3%, specificity 55.6%, PPV 52.4%, NPV 75.8 and total accuracy 62.7% for prediction of refractory group.
Summary
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Our study showed that PGP expression in refractory group was significantly increased among patient with onset of disease during neonatal period than those with age of onset during infancy and childhood, while non-significant relation with other studied parameters (sex, perinatal problems, family history of seizure, consanguinity, developmental history, post-natal problems or mode of delivery).
We concluded that P-gp serum levels in patients with DRE were significantly elevated compared to patients with medically controlled epilepsy and non-epileptic children. So it is important to study samples at diagnosis and after treatment, especially for those patients who remain refractory to therapy, to understand efflux capacity of P-gp function.