ملاتونین در آنالیز پیچیده توبروز اسکلروزیس با استفاده از روش های مدلسازی مدرن ریاضی / Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods

ملاتونین در آنالیز پیچیده توبروز اسکلروزیس با استفاده از روش های مدلسازی مدرن ریاضی Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods

  • نوع فایل : کتاب
  • زبان : انگلیسی
  • ناشر : Hindawi
  • چاپ و سال / کشور: 2018

توضیحات

رشته های مرتبط پزشکی
گرایش های مرتبط غدد و متابولیسم
مجله بین المللی غدد درون ریز – International Journal of Endocrinology
دانشگاه Department of Pediatric Neurology – Medical University of Silesia – Poland
شناسه دیجیتال – doi https://doi.org/10.1155/2017/8234502
منتشر شده در نشریه هینداوی

Description

1. Introduction Tuberous sclerosis complex (TSC) affects 1 in 6000 live births. It is caused by mutation in a tumor suppressor gene: either the TSC1 gene on chromosome 9 or the TSC2 gene on chromosome 16; however, larger “genomic” mutations are very rare in TSC1 and more common in TSC2, occurring in about 6% of all TSC patients [1]. A mutation can be found in 85% of patients, and the total number of unique DNA variants of over 850 and 2400 for TSC1 and TSC2, respectively, has been shown to cause TSC up to date (Tuberous Sclerosis Database, http://chromium.liacs.nl/LOVD2/TSC/ home.php). About 85%–90% of children and adolescents with TSC have CNS symptoms including epilepsy, cognitive impairment, behavioral problems, and autism-like symptoms [1, 2]. Epilepsy usually begins during the first year of life, frequently with focal seizures, tonic clonic or myoclonic seizures, or epileptic spasms. TSC patients may experience all kinds of seizures, which can become intractable over time [1]. Mutations in the TSC1 or TSC2 genes lead to disruption of the TSC1–TSC2 intracellular protein complex. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mammalian target of rapamycin (mTOR) protein complex [3]. The recognition of the role of mTOR pathway upregulation in TSC-associated lesions opens new possibilities for treatment strategy. Probably, mTOR inhibitors may not only suppress seizures, but also influence/reduce the epileptogenesis [4]. The etiology of sleep problems, frequently observed in TSC, remains unclear [5]. In children with TSC, severe sleep problems usually appear after the onset of epileptic spasms and are often due to sleep-related epileptic events (night waking, early waking, seizure-related sleep problems, and excessive daytime sleepiness) [5, 6]. Blunted melatonin (MLT) blood levels are especially interesting for their potential, yet unproven link with the disrupted sleep-wake cycle is frequently seen in many TSC children. In healthy subjects, melatonin secretion by the pineal gland increases prior to sleep onset and a peak is seen 4-5 hours after sleep onset. The circadian melatonin secretion in patients with epilepsy is characterized by an increased phase shift of melatonin release as compared to the nonepileptic patients [7]. Thus, since seizures are the most common neurological symptom of TSC, occurring in 96% children, similar disturbances may also be expected in TSC. However, to our knowledge, no one has looked at the circadian rhythms of melatonin production in children with TSC. In order to fill this literature gap, we decided to record the circadian melatonin secretion rhythms in TSC children and to analyze the data using the mathematical modelling proposed previously in our study of circadian rhythms of endogenous melatonin secretion in patients with epilepsy [7]. The parameters describing the diurnal melatonin secretion, melatonin concentration, release amplitude, phase shift of melatonin release, and sleep duration in children with TSC were compared with the data obtained for children with and without epilepsy. In addition, the mathematical model determines the dim light melatonin onset (DLMO) of melatonin secretion, as an important circadian marker [8].
اگر شما نسبت به این اثر یا عنوان محق هستید، لطفا از طریق "بخش تماس با ما" با ما تماس بگیرید و برای اطلاعات بیشتر، صفحه قوانین و مقررات را مطالعه نمایید.

دیدگاه کاربران


لطفا در این قسمت فقط نظر شخصی در مورد این عنوان را وارد نمایید و در صورتیکه مشکلی با دانلود یا استفاده از این فایل دارید در صفحه کاربری تیکت ثبت کنید.

بارگزاری