Deneysel rat omuriliği yaralanma modelinde methotrexat-etanercept kombinasyonunun tedavi edici ve koruyucu etkilerinin değerlendirilmesi
Küçük Resim Yok
Tarih
2014
Yazarlar
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Cilt Başlığı
Yayıncı
Bolu Abant İzzet Baysal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş: Travmatik omurilik yaralanması (TOY) ani ve beklenmedik şekilde oluşan; son derece yıkıcı, sakatlayıcı; kişisel ve toplumsal açıdan yüksek maliyetlere; psikolojik ve sosyolojik sorunlara neden olan bir olay olarak tanımlanabilir. Gelişen tıbbi bakım, morbidite ve mortaliteyi iyileştirmiş olmasına rağmen, nöronal hasarın sınırlanması ve rejenerasyonun uyarılması amacıyla yapılan farmakoterapideki gelişmeler ise hala sınırlıdır. Preklinik çalışmalarda başarılı tedavi modalitelerinin çoğunun, klinik çalışmalarda sınırlı başarı elde etme nedenlerinden birisi, primer mekanik yaralanmanın tetiklediği sekonder dejeneratif yanıtın karmaşıklığıdır. Çünkü birçok monoterapi sekonder yaralanma mekanizmasının yalnızca bir aşamasını etkilemektedir. Oysa başarılı tedavi bu mekanizmanın birçok aşamasında etkili olmalıdır. Bu nedenle kombine tedavi uygulamaları klinik ve deneysel bazda daha öncelikli düşünülmeye başlanmıştır. Bu çalışma SKY'ında Etanersept+Methorexat(MTX) kombinasyonunun eş zamanlı kullanımının sinerjik bir etki yaratıp yaratmadığını anlamak için gerçekleştirilmiştir. Methot: Bu çalışmada klip kompresyon yöntemi kullanılarak oluşturulan omurilik yaralanmaları histolojik(Luxol fast hematoxilen-eozin ve TUNEL boyama yöntemleri) ve nörolojik muayene yöntemleri ( Eğik düzlem ve motor skorlama) kullanılarak Etanercept, methotrexat ve etanercept+methotrexat kombinasyonlarının ikincil hasar üzerindeki koruyucu ve tedavi edici etkinlikleri araştırıldı. Çalışmada 30 adet sprague Dawley cinsi dişi erişkin rat kullanıldı. Anesteziyi takiben T7-9 (torakal) mesafesinden yapılan cilt insizyonu ve paravertebral adaleler sıyrıldı. Grup 1(kontrol), grup 2 (laminektomi+kord basısı),grup 3 (laminektomi+kord basısı+etanercept), grup 4 (laminektomi+kord basısı+methotrexat), grup 5 (laminektomi+kord basısı+etanercept+methotrexat) verilen 6'şar rattan oluşan toplam 5 grup oluşturuldu. Deneklerin 1, 3, 5 ve 10. günlerde eğik düzlem ve motor skorları değerlendirildi. Histopatolojik değerlendirme için 10. gün sakrifiye edildiler. Bulgular: Her iki monoterapi grubunun travma grubuna göre klinik bulgularda istatistiksel anlamda belirgin düzelme ve buna uyumlu şekilde histolojik bulgularda istatistiksel anlamda nekroz ve apoptozis oranlarında belirgin baskılanma sağlanmıştır. Her iki monoterapi grubunun karşılaştırmalarında klinik ve histolojik bulgulara göre aralarında istatistiksel anlamda farklılığın olmadığı, ancak etanercept lehine kısmi bir farklılığın olduğu görülmüştür. Kombine terapi grubunun travma grubu ile karşılaştırılmasında klinik bulgular ve apoptozis açısından istatistiksel anlamda kombine tedavi lehine; mono terapiler ile karşılaştırılmasında ise kombine tedavinin histolojik (nekroz ve apoptozisin baskılanması) olarak istatistiksel anlamda monoterapi gruplarına üstünlük sağlamasına karşın klinik anlamda bu farklılığın görülmediği ortaya konmuştur. Sonuç: Gerek çalışmamızdaki denek sayısının; gerekse literatürde yapılan çalışma sayısının çok sınırlı olması methotrexat+etanercept kombinasyonunun etkilerinin net olarak ortaya konmasına engel olmaktadır. Bu nedenle daha fazla sayıda deneysel ve klinik çalışmanın yapılması gereklidir.
Introduction: Traumatic spinal injury (TSI) is defined as a sudden, devastating, debilitating event which causes highly valued personal and social costs; and physiological, sociological problems. Even though advancements in medical care have improved rates of morbidity and mortality, progress in pharmacotherapy which has been developed to stimulate regeneration and restrict neuronal damage, is still limited. One reason for treatment modalities, which have been successful in preclinical trials, to end up with limited results in clinical studies, is the complexity of the secondary degenerative response which has been triggered by the primary mechanical injury. Most of the mono-therapies affect, only one stage of the secondary injury mechanism; whereas a successful treatment should be effective in many stages. Therefore combined therapy practices are being prioritized in clinical and experimental trials. This study is designed to understand if Etanercept+Methotrexate combination in TSI has any synergistic effects or not. Methods: In this study with the use of histological (Luxol fast hematoxylin-eosin and TUNEL dying) and neurological examination (Inclined plane and motor scoring) methods; preservative and therapeutic efficacies of Etanercept, Methotrexate and Etanercept+Methotrexate combination in secondary injury are being investigated on spinal injury models which have been created by clip compression technique. 30 Sprague Dawley breed mature female rats were exploited in this study. Following the anesthesia, with a skin incision through the space between T7-T9 (thoracal vertebras), paravertebral muscles were dissected; and five groups, 6 rats in each, were comprised: group 1 (the control group), group 2 (laminectomy + cord compression), group 3 (laminectomy + cord compression + Etanercept), group 4 (laminectomy + cord compression + Methotrexate) and group 5 (laminectomy + cord compression + Etanercept + Methotrexate). Subjects were evaluated at days 1, 3, 5 and 10 for their inclined plane and motor scores. All were sacrificed at day 10 for the histopathological examination. Findings: Regarding the clinical findings, in each mono-therapy group with respect to trauma group, a significant recovery, and in correspondence to that a significant reduction of necrosis and apoptosis rates in histological results were found. When two mono-therapy groups were compared, there was no significant difference in clinical and histological manners, whereas a partial difference was observed in favor of Etanercept. In comparison of combination therapy group verses trauma group, a significant difference in the favor of combination therapy -regarding the clinical findings and apoptosis- was found. When compared with the mono-therapies, combination therapy is found to be significantly superior to mono-therapy groups in histological aspect (necrosis and apoptosis reduction), whereas this superiority cannot be kept in clinical sense. Results: Neither the number of subjects in our trial nor the quantity of studies in the literature is efficient enough to clearly manifest the effects of Methotrexate + Etanercept combination in TSI. Therefore more experimental and clinical studies are needed to be accomplished.
Introduction: Traumatic spinal injury (TSI) is defined as a sudden, devastating, debilitating event which causes highly valued personal and social costs; and physiological, sociological problems. Even though advancements in medical care have improved rates of morbidity and mortality, progress in pharmacotherapy which has been developed to stimulate regeneration and restrict neuronal damage, is still limited. One reason for treatment modalities, which have been successful in preclinical trials, to end up with limited results in clinical studies, is the complexity of the secondary degenerative response which has been triggered by the primary mechanical injury. Most of the mono-therapies affect, only one stage of the secondary injury mechanism; whereas a successful treatment should be effective in many stages. Therefore combined therapy practices are being prioritized in clinical and experimental trials. This study is designed to understand if Etanercept+Methotrexate combination in TSI has any synergistic effects or not. Methods: In this study with the use of histological (Luxol fast hematoxylin-eosin and TUNEL dying) and neurological examination (Inclined plane and motor scoring) methods; preservative and therapeutic efficacies of Etanercept, Methotrexate and Etanercept+Methotrexate combination in secondary injury are being investigated on spinal injury models which have been created by clip compression technique. 30 Sprague Dawley breed mature female rats were exploited in this study. Following the anesthesia, with a skin incision through the space between T7-T9 (thoracal vertebras), paravertebral muscles were dissected; and five groups, 6 rats in each, were comprised: group 1 (the control group), group 2 (laminectomy + cord compression), group 3 (laminectomy + cord compression + Etanercept), group 4 (laminectomy + cord compression + Methotrexate) and group 5 (laminectomy + cord compression + Etanercept + Methotrexate). Subjects were evaluated at days 1, 3, 5 and 10 for their inclined plane and motor scores. All were sacrificed at day 10 for the histopathological examination. Findings: Regarding the clinical findings, in each mono-therapy group with respect to trauma group, a significant recovery, and in correspondence to that a significant reduction of necrosis and apoptosis rates in histological results were found. When two mono-therapy groups were compared, there was no significant difference in clinical and histological manners, whereas a partial difference was observed in favor of Etanercept. In comparison of combination therapy group verses trauma group, a significant difference in the favor of combination therapy -regarding the clinical findings and apoptosis- was found. When compared with the mono-therapies, combination therapy is found to be significantly superior to mono-therapy groups in histological aspect (necrosis and apoptosis reduction), whereas this superiority cannot be kept in clinical sense. Results: Neither the number of subjects in our trial nor the quantity of studies in the literature is efficient enough to clearly manifest the effects of Methotrexate + Etanercept combination in TSI. Therefore more experimental and clinical studies are needed to be accomplished.
Açıklama
Tıp Fakültesi, Beyin ve Sinir Cerrahisi Ana Bilim Dalı
Anahtar Kelimeler
Nöroşirürji, Neurosurgery
