Levetirasetam ve lamotrijin'in sıçanlarda ilk trimesterdeki nöral tüp gelişimi ve nöral krest hücre göçü üzerine etkilerinin incelenmesi
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Bu doktora tez çalışmasında farklı mekanizmalara sahip antiepileptik ilaçların düşük ve yüksek dozlarının nörülasyonda ve nöral krest hücre migrasyonu sırasında etkileri incelenmesi amaçlanmıştır. Uzun vadede genel amaç ise insan sağlığının ön planda olduğu, ailelerin sosyal ve medikal refahlarına katkı sağlanması amacıyla literatürde olmayan yaygın ajanların düşük ve yüksek doz, literatürde güvenli sayılan ajanların yüksek doz embriyolojik verilerinin elde edilmesidir. Yöntem olarak gebelik öncesi takip bütün döngünün dikkatle incelendiği sitopatoloji ile, gebelik takibi ise ultrasonografik yöntemlerle yapılmıştır. Anne ağırlıkları düzenli olarak kontrol edilmiştir. Histolojik verilerin oluşturulması amacıyla rutin histolojik yöntemler kullanılmış ve dokular parafin bloklara gömülmüştür. Fetüs kesitleri genel morfolojik gözlem için Hematoksilen&Eozin ve Cresyl-Echt Violet ile immünohistokimyasal bulgular için ise SHH, SOX2, SOX10, Nestin ve p75 belirteçleriyle boyanmıştır. Bu boyamaların sonucunda ifadenin artış ve azalışına ve bu alterasyonların konumuna bağlı olarak kök hücre karakteri ve fetüsteki göç yolları hakkında morfolojik veri elde edilmiştir. Bu verileri protein miktarıyla desteklemek için ise SHH, SOX2 ve TNGFR belirteçleriyle ELISA testleri yapılmıştır. Literatürü incelediğimizde yeni nesil anti-epileptik ilaçların güvenli olduğu kanısnın ağır bastığı görülmekle beraber, bu çalışmaların detaylandırılması gerektiği fikriyle özgün belirteçler ve yöntemler kullanılarak normal altı ve çok üstü olmak üzere iki doz seçilmiştir. Normalin altı dozun seçilmesinde amaç güvenli bir ajanda neredeyse hiç kullanılmamışa yakın etki görmek, normalin çok üstü seçimde ise amaç ekstrem vakalar için model oluştumakla beraber olası hasarları gözlemlemek için toksisiteyi yüksek tutmaktır. Düşük doz için bulgular literatürle uyumlu şekilde anti-epileptik ilaçların etkilerinin neredeyse hiç kullanılmamış kadar güvenli olduğunu, aşırı dozlarda ise bir takım patolojik değişiklikler ve migratif bozukluklar gözlemlenebileceğini ortaya koymuştur. Aşırı dozda görülen gelişim farklarını irdeleyerek migrasyon meaknizmaları anlaşılmaya gayret edilmiştir. Sonuç olarak ilacın literatürdeki kadar güvenli olduğu saptanmış, aşırı yüksek doz sadece migratif yolların bozulmasıyla gözlenecek sonuçlar için ileri çalışmalar yapılması gerektiğini göstermiştir
In this doctoral thesis, it was aimed to examine the effects of low and high doses of anti-epileptic drugs with different mechanisms on neurulation and during neural crest cell migration. The long-term general aim is to obtain low and high-dose embryological data of common agents that are not in the literature and high-dose of agents considered safe in the literature in order to contribute to the social and medical well-being of families, where human health is at the forefront. As a method, pre-pregnancy follow-up was done with cytopathology, in which the whole cycle was carefully examined, and pregnancy follow-up was made with ultrasonographic methods. Maternal weights were checked regularly. Routine histological methods were used to generate histological data and tissues were embedded in paraffin blocks. Fetus sections were stained with Hematoxylin§Eosin and Cresyl-Echt Violet for general morphological observation and with SHH, SOX2, SOX10, Nestin and p75 markers for immunohistochemical findings. As a result of these stainings, morphological data were obtained about the stem cell character and migration routes in the fetus, depending on the increase and decrease in expression and the location of these alterations. In order to support these data with the amount of protein, ELISA tests were performed with SHH, SOX2 and TNGFR markers. When we examine the literature, it is seen that the opinion that the new generation anti-epileptic drugs are safe dominates, but with the idea that these studies should be detailed, two kind doses, below normal and very high, were selected by using specific markers and methods. The purpose of choosing a subnormal dose is to see an effect close to almost never used in a safe agent, and in choosing a very high normal dose, the aim is to keep the toxicity high in order to observe possible damage, while forming a model for extreme cases. Findings for low doses revealed that the effects of anti-epileptic drugs are almost as safe as they have never been used, in line with the literature, and some pathological changes and migratory disorders can be observed in overdoses. It has been tried to understand the migration mechanisms by examining the developmental differences seen in overdose. As a result, it was determined that the drug is as safe as in the literature, and it showed that further studies are required for the results to be observed only with the disruption of the migratory pathways at excessively high doses.
In this doctoral thesis, it was aimed to examine the effects of low and high doses of anti-epileptic drugs with different mechanisms on neurulation and during neural crest cell migration. The long-term general aim is to obtain low and high-dose embryological data of common agents that are not in the literature and high-dose of agents considered safe in the literature in order to contribute to the social and medical well-being of families, where human health is at the forefront. As a method, pre-pregnancy follow-up was done with cytopathology, in which the whole cycle was carefully examined, and pregnancy follow-up was made with ultrasonographic methods. Maternal weights were checked regularly. Routine histological methods were used to generate histological data and tissues were embedded in paraffin blocks. Fetus sections were stained with Hematoxylin§Eosin and Cresyl-Echt Violet for general morphological observation and with SHH, SOX2, SOX10, Nestin and p75 markers for immunohistochemical findings. As a result of these stainings, morphological data were obtained about the stem cell character and migration routes in the fetus, depending on the increase and decrease in expression and the location of these alterations. In order to support these data with the amount of protein, ELISA tests were performed with SHH, SOX2 and TNGFR markers. When we examine the literature, it is seen that the opinion that the new generation anti-epileptic drugs are safe dominates, but with the idea that these studies should be detailed, two kind doses, below normal and very high, were selected by using specific markers and methods. The purpose of choosing a subnormal dose is to see an effect close to almost never used in a safe agent, and in choosing a very high normal dose, the aim is to keep the toxicity high in order to observe possible damage, while forming a model for extreme cases. Findings for low doses revealed that the effects of anti-epileptic drugs are almost as safe as they have never been used, in line with the literature, and some pathological changes and migratory disorders can be observed in overdoses. It has been tried to understand the migration mechanisms by examining the developmental differences seen in overdose. As a result, it was determined that the drug is as safe as in the literature, and it showed that further studies are required for the results to be observed only with the disruption of the migratory pathways at excessively high doses.
Açıklama
13.03.2023 tarihine kadar kullanımı yazar tarafından kısıtlanmıştır
Anahtar Kelimeler
Histoloji ve Embriyoloji, Histology and Embryology
