The role of oxidative stress and antioxidants in the pathogenesis of age-related macular degeneration

OBJECTIVE: To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration. METHOD: The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration. RESULT: The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05). CONCLUSION: The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration

Backpage v. Hawley

ATTORNEY GENERAL JOSHUA D. HAWLEY’S MOTION FOR CRIMINAL CONTEMPT AND CIVIL SANCTIONS AGAINST BACKPAGE.COM, LLC AND MEMORANDUM IN SUPPOR

The Comparison of The Efficacy and Safety of Original and Biosimilar Filgrastim in Prevention of Chemotherapy-Induced Neutropenia in Children with Cancer

Conclusion: The biosimilar filgrastim, Leucostim, is as effective and safe as the original drug for prophylaxis of chemotherapy-induced neutropenia in children

The Hidden Though Flourishing Justification of Intellectual Property Laws: Distributive Justice, National Versus International Approaches

Bu çalışmada, Gökkuşağı alabalıklarında enfeksiyonoluşturan Ichthyophthirius multifiliis’infarklı bölgelerden izole edilmiş saha suşlarının genotipik yapıları temelindeimmundominant özellik gösteren rekombinant immobilizan antijenlerini(i-antijen) kodlayan genlerin bakteriyel ekspresyon sistemine klonlanarakeksprese ve karakterize edilmeleri, antijenik profillerinin ortaya çıkarılmasıve aşı adayı olabilecek rekombinant antijenlerin elde edilmesi amaçlanmıştır.&nbsp;Çalışmada 2018 ve 2019 yıllarının Temmuz ve Ağustos ayları arasında Gökkuşağıalabalığı yetiştiriciliğinin yoğun yapıldığı Samsun, Rize, Kayseri, Elazığ,Burdur, Antalya ve Muğla illerinde bulunan işletmeler ziyaret edilerek balıkpopülasyonları üzerinde saha araştırmaları yürütülmüş ve I. multifiliis ile enfekte bulunan balıklardan ilgili protokolleregöre izolasyon gerçekleştirilmiştir. Laboratuvara uygun solüsyonlar ve soğukzincir altında intikal ettirilen örneklerden cDNA ve gDNA izolasyonlarıgerçekleştirilmiştir. I. multifiliis i-antijengen lokusunun amplifikasyonu amacıyla optimum primer dizaynı için ön çalışmalaryürütülmüş ve hedef gen bölgeleri uygun amplifikasyon koşullarında PCR’daçoğaltılmıştır. Elde edilen amplikonlar agaroz jel üzerinden saflaştırılmıştır.Multiple gen lokusu sekanslarının belirlenebilmesi amacıyla ilgili pürifiyeamplikonlar pJET 1.2 plazmit vektörüne CloneJET PCR cloning kit (Thermo FisherScientific) kullanılarak klonlanmış ve katı besi yerinde belirlenenkolonilerden rekombinant plazmid DNA izolasyonları gerçekleştirilmiştir. Rekombinantplazmidler spesifik primerlerle çift yönlü olarak sekanslanmış vekromotogramlar De Novo Assemble üzerinden işlenerek hedef insert sekanslarvektör plazmid DNA’sı içerisinden çıkarılmış ve konsensüs sekanslar eldeedilmiştir. İlgili primerlerin i-antijen gen lokusu içerisinde çoğalttığı fragmentlerinbelirlenebilmesi amacıyla PCR ürünleri ayrıca yeni nesil dizileme teknolojisi (NGS)kullanılarak işlenmiş ve elde edilen dizilimlerin gen veri tabanlarındakimevcut tüm i-antijen gen lokusları ile filogenetik ilişkileri araştırılmıştır.Tüm bu araştırmalar sonucu karakterize edilen i-antijen genlerinin ekspreseettiği proteinlerin rekombinant olarak eldesi için çalışmalargerçekleştirilmiştir. Aşı adayı potansiyeli olabilecek bazı lokusların bakteriyelekspresyon sistemine aktarımı için kodon optimizasyonları yapılarak pET-32a(+)ekspresyon plazmid DNA’sına (Novagen) klonlanması gerçekleştirilmiştir. Eldeedilen rekombinant plazmitler E. colikompotent BL21(DE3) hücrelerine transforme edilerek optimum koşullardaekspresyon çalışmaları yürütülmüş ve ekspresyon etkinliği SDS-PAGE ve WesternBlot analizleri ile belirlenmiştir. Eksprese edilen rekombinant i-antijenproteinleri afinite kromotografi kulanılarak saflaştırılmış ve immunreaktiflikleri Western Blot analizleri ile tespit edilmiştir.&nbsp;Çalışmada,Elazığ, Rize ve Muğla illerinde ziyaret edilen işletmelerdeki Gökkuşağıalabalıklarında deri ve solungaçlarından hazırlanan preparatların mikroskobikincelemeleri ile I. multifiliisenfeksiyonunun yaygın olduğu görülmüştür. İlgili bölgelerden elde edilen I. multifiliis suşlarına ait cDNA vegDNA izolatlarının i-antijen gen lokusunun dizayn edilen pirmerlerle PCR’daamplifiye edilmesi sonucu 1200-1300 bp büyüklüğünde amplikonlar saptanmıştır.Pürifiye amplikonların klonlanması sonucu ilgili izolatlara ait açık okumaçerçevesi (ORF) sekanslarının analizinde birbirleriyle %38,3-58,8 arasındafarklılık gösteren 4 farklı i-antijen izoformu tespit edilmiştir. Bu izoformlararasında bir antijenik lokusun (ImulTR1-iant) her üç ildeki alabalıkpopülasyonlarından izole edilen I.multifiliis suşlarında da var olduğu NGS analizlerinde görülmüştür.ImulTR1-iant ORF sekansı ayrıca Amerika Birleşik Devletleri’nde alabalıklardanizole edilmiş bir i-antijen izoformuyla %83,3 identiklik gösterirken, diğertespit edilen izoformlara ait sekansların GenBank veri tabanında mevcuti-antijen sekanslarından oldukça farklı olduğu belirlenmiştir. Araştırmadarekaombinant i-antijen eldesi için yaygın belirlenen ImulTR1-iant izolatıüzerinden analizler yürütülmüştür. Bu izoformu kodlayan gen bölgesinin 1263bpbüyüklüğünde olduğu ve ORF’nin 420 amino asitten teşekkül ettiğibelirlenmiştir. ORF amino asit sekanslarının in-slico analizlerde 42,552 kDabüyüklüğünde bir proteini eksprese ettiği, bu proteinin sitoplazmik olduğu vetransmembran bölge içermediği tespit edilmiştir. Ayrıca ilgili ORF sekansıiçerisinde uzunluğu 7-22aa arasında değişen 21 antijenik bölge olduğubelirlenmiştir. Kodon optimizasyonu yapılmış olan ImulTR1-iant izoformuna ait pET-32a(+)rekombinant plazmitinin E. colikompotent BL21(DE3) hücrelerine transformasyonu ve ekspresyonu sonrasındayapılan SDS-PAGE analizlerinde in-silico analiz sonuçlarına paralel olarakyaklaşık 43kDa’luk protein jel üzerinde görüntülenmiştir. İlgili rekombinantprotein afinite kromotografide HisTrap FF crude (GE Healthcare) kolonlarıkullanılarak saflaştırılmış ve pürifiye rekombinant antijenin immun-reaktifliğiWestern-Blot analizleriyle gösterilmiştir.&nbsp;ErciyesÜniversitesi Bilimsel Araştırma Projeleri Birimi tarafından TOA-2017-7742 kodnumarasıyla desteklenen bu çalışma ile Türkiye’de gökkuşağı alabalıklarındasorun oluşturan ve ekonomik kayıplara yol açan I. multifiliis suşlarına karşı biyoteknolojik aşı geliştirilmesinoktasında aşı adayı olabilecek immobilizan antijenler üzerine özgün veriler sağlanmıştır.Elde edilen aşı adayı rekombinant antijenlerin etkinliğini ortaya koymanoktasında laboratuvar ve saha şartlarında immunizasyon ve çelınç enfeksiyondenemeleri için yeni proje çalışmaları planlanmaktadır.</style

Local and systemic effects of adrenomedullin after intestinal ischemia reperfusion

Adrenomedullin (AM) is a peptide proven to increase cellular tolerance to hypoxia and oxidative stresss and contribute angiogenesis. Despite its known therapeutic effects on myocardial, renal or spinal ischemic reperfusion injuries, its local and systemic effects on intestinal ischemic reperfusion injury still remain unknown. This study aims to demonstrate the local and systemic effects of AM on Intestinal Ischemic Reperfusion Injury (I-IRI) demonstrated in rats. Thirty male rats were randomly allocated to five groups: Control, Adrenomedullin (AM), Intestinal Ischemic Reperfusion Injury (I-IRI), Adrenomedullin and Intestinal Ischemic Reperfusion Injury (AM+I-IRI), and Intestinal Ischemic Reperfusion Injury and Adrenomedullin (I-IRI+AM). Blood and tissue samples were obtained for biochemical and histopathological evaluation. The results were expressed as mean±SEM and, P &lt;0.05 was considered statistically significant. The levels of inflammatory cytokines were found to be elevated in I-IRI group and depleted in I-IRI+AM group. The biochemical and histopathological markers of injuries at the intestine and remote organs were found to be recuperated when the AM applied before the reperfusion phase. Results of this study demonstrated that the therapeutic drug adrenomedullin (AM) could reverse the intestinal and remote organ injuries related to intestinal ischemic reperfusion injury (I-IRI). These effects might be related to the antioxidant, anti-inflammatory, and anti-apoptotic activities of AM

Актуальные вопросы развития правового регулирования арбитража (третейского разбирательства) в Российской Федерации

В магистерской диссертации ставились следующие цели и задачи: Целью работы является изучение теоретических и практических проблем, связанных с отдельными вопросами арбитрабельности споров в развитии законодательства и судебной практики. Актуальность вопроса вызвана произошедшей в 2015-2016 гг. в РФ реформой третейского разбирательства, связанной с принятием Федерального закона от 29.12.2015 № 382-ФЗ «Об арбитраже (третейском разбирательстве) в Российской Федерации» и Федерального закона от 29.12.2015 № 409-ФЗ «О внесении изменений в отдельные законодательные акты Российской Федерации и признании утратившим силу пункта 3 части 1 статьи 6 Федерального закона „О саморегулируемых организациях“ в связи с принятием Федерального закона „Об арбитраже (третейском разбирательстве) в Российской Федерации». В основу исследования легли правовые позиции, выраженные в Постановлении Президиума ВАС РФ от 11.02.2014 № 11059/13 по делу № А26-9592/2012, а также отдельных выводов, сформулированных в Определениях КС РФ от 15.01.2015 № 5-О и от 29.09.2015 № 2214-О, касающихся вопросов установления критериев, позволяющих сделать вывод о неарбитрабельности споров, возникающих из природоресурсных договоров, и, в частности, из такого основания для возникновения специального права лесопользования, как договор аренды лесного участка, заключенного в целях заготовки древесины. Помимо вышеуказанного, к задачам и целям исследования относятся: 1. Обзор существующих в доктрине права третейского разбирательства научных взглядов и представлений об институте арбитрабельности споров, их краткая характеристика. Изложение автором собственной позиции в отношении критериев арбитрабельности. 2. Характеристика лесных имущественных правоотношений, основанных на договорных основаниях возникновения права природопользования. Исследование вопроса арбитрабельности споров, возникающих из лесных имущественных правоотношений, с позиции материально-правового (позитивного) критерия установления арбитрабельности. Анализ стадий заключения, исполнения, расторжения договора аренды лесного участка, а также признания его недействительным. 3. Исследование вопроса о допустимости передачи гражданско-правового спора, возникшего из лесных имущественных правоотношений, на рассмотрение в третейский суд с позиции обеспечения необходимых гарантий прав участников юрисдикционного процесса в рамках процессуальной формы арбитража, в её соотношении с судопроизводством, осуществляемом по правилам АПК РФ и ГПК РФ. Выводы, сделанные по результатам исследования: • Изменения, внесенные в правовое регулирование арбитража в результате третейской реформы, позволяют расширить категории споров, относимых к компетенции третейского суда ввиду «юридизации» процедуры третейского разбирательства с одной стороны, и усиления диспозитивных начал в определении правил арбитража – с другой. • Ввиду особенностей третейского процесса, следует согласиться с позицией ВАС РФ о том, что споры, возникающие на стадии заключения договора аренды лесного участка, в настоящий момент являются неарбитрабельными по причине необходимости учёта законных интересов заведомо неопределённого круга лиц – потенциальных участников аукциона по продаже права на заключение договора аренды лесного участка. Представляется, что соответствующая позиция правомерна до принятия изменений в законодательном регулировании, обеспечивающих учет интересов широкого круга субъектов при обращении за юрисдикционной защитой в третейский суд – по аналогии с арбитражем корпоративных споров. • Публичный интерес РФ, субъектов РФ, выражающийся в необходимости соблюдения природоохранных требований, а также в администрировании неналоговых доходов бюджетов, не может являться аргументом в признании данной категории споров неарбитрабельными. Данный публичный интерес в конкретном деле, рассмотренном ВАС РФ, не сводим к содержанию «публичного порядка», либо «основополагающих принципов российского права», являющимися безусловными основаниями для отмены решения третейского суда. Аналогичный вывод следует и применительно к объекту лесного правоотношения – земельного участка лесного фонда. • Процессуальная форма арбитража как до проведения третейской реформы, так и после неё позволяет отнести к категории арбитрабельных споров, возникающих в связи с исполнением, изменением, расторжением договора аренды лесного участка, признания его недействительным, поскольку стороны третейского соглашения вправе предъявлять повышенные требования к механизму юрисдикционной защиты прав участника арендного правоотношения, а также приспособить процедуру третейского разбирательства к особенностям экономической деятельности в сфере лесного хозяйства. • С учетом судебной практики Европейского Суда по правам человека, заключение сторонами арбитражного соглашения рассматривается как допустимое в определенной степени ограничение права на судебную защиту. В связи с этим, стороны арбитражного соглашения, признавая компетенцию третейского суда по окончательному разрешению гражданско-правового спора, несут повышенный риск совершения, либо не совершения ими необходимых процессуальных действий, в том числе при выборе арбитра. Вынесенное третейским судом решение по существу обладает свойством обязательности для сторон, выражающейся, в том числе, в запрете последующего пересмотра данного решения по существу. По обстоятельствам дела, рассмотренного ВАС РФ, действия проигравшей арбитраж стороны были направлены на преодоление окончательного решения третейского суда и представляли собой злоупотребление правом. В свою очередь, ВАС РФ необоснованно не применил в отношении заявления проигравшей спор стороны правило эстоппель, применимое и в процессуальных правоотношениях.In the master's thesis, the following goals and tasks were set: The aim of the work is to study theoretical and practical problems related to specific issues of arbitrability in the development of legislation and judicial practice. The urgency of the issue is caused by happened in 2015-2016. in the Russian Federation the reform of arbitration proceedings related to the adoption of Federal Law No. 382-FZ of December 29, 2015 "On Arbitration (Arbitration) in the Russian Federation" and Federal Law No. 409-FZ of December 29, 2015 "On Amending Certain Legislative Acts of the Russian Federation and the invalidation of paragraph 3 of Part 1 of Article 6 of the Federal Law "On Self-Regulating Organizations" in connection with the adoption of the Federal Law "On Arbitration (Arbitration Proceedings) in the Russian Federation". The research was based on the legal positions expressed in the Resolution of the Presidium of the Supreme Arbitration Court of the Russian Federation of 11.02.2014 No. 11059/13 in the case No. A26-9592 / 2012, as well as certain conclusions formulated by Constitutional Court of RF, Decrees No. 5-O of 15.01.2015 and 09/29/2015 № 2214-О, concerning the issues of establishing criteria allowing to conclude, that the disputes, arising from nature resources contracts are not arbitrary, and in particular from such grounds for the emergence of a special forest use right, as a lease contract for a forest plot, concluded for the purpose of harvesting timber . Besides the above-mentioned, there are following goals and tasks of the research: 1. Review of existing in the doctrine of the right of arbitration proceedings of scientific views and representations about the institution of arbitrability of disputes, their brief description. The author's statement based on his own position with respect to the criteria of arbitrability. 2. Characteristics of forest proprietary relations, based on the contractual grounds for the emergence of the right to use nature. Investigation of the issue of arbitrability of disputes arising from forest proprietary relations, from the position of a substantive (positive) criterion for establishing arbitrability. Analysis of the stages of conclusion, execution, cancellation of the lease contract for the forest plot, and its recognition as invalid. 3. Investigation of the issue of the admissibility of the transfer of a civil dispute, arising out from a forest property relations to the arbitration court, for ensuring the necessary guarantees of the rights of participants in the jurisdictional process within the procedural form of arbitration, in its relation to legal proceedings, carried out per rules of Arbitrage Procedural Code and Civil Procedural Code of Russian Federation. Conclusions drawn from the study: • The changes made to the legal regulation of arbitration because of the arbitration reform make it possible to expand the categories of disputes falling within the competence of the arbitral tribunal due to the "legalization" (formalizing) of the arbitration procedure on the one hand, and the strengthening of the discretionary principles in determining arbitration rules, on the other. • Due to the peculiarities of the arbitrage, we should agree with the position of the Supreme Arbitration Court of RF, that the disputes, arising at the stage of concluding the lease contract for the forest plot are currently non-arbitrable, considering the legitimate interests of an uncertain circle of potential participants in the auction for the sale of the right to concluding a lease agreement for a forest plot. It seems, that the corresponding position is legitimate until be made changes in the legislative regulation, that ensure the consideration of the interests of a wide range of subjects, applying for jurisdictional protection in an arbitrage - by analogy with arbitration of corporate disputes. • The public interest of the RF, RF subjects, expressed in the propositions of complying by land plot leaser environmental requirements, as well as in the administration of non-tax revenues of budgets, cannot be an argument in recognizing this category of disputes as non-arbitrable. This public interest in a case, considered by the Supreme Arbitration Court of the Russian Federation is not reduced to the content of "public policy" or "fundamental principles of Russian law", which are unconditional grounds for canceling the decision of the arbitral tribunal. A similar conclusion follows also regarding to the object of the forest legal relationship - the land plot of the forest fund. • Remedial form of arbitration as before the arbitration reforms, and after them can be attributed to the category of arbitrability of disputes, arising about the execution, modification, cancellation of lease agreement, annulment; as for the parties of the arbitration agreement causes to demand higher mechanism jurisdictional protect the rights of parties, as well as to adapt the arbitration procedure to the peculiarities of the economic activity in the forestry. • Considering the judgment practice of the European Court of Human Rights, conclusion by the parties the arbitration agreement is considered as valid to some extent, restrictions on the right to judicial protection. In this regard, the parties of the arbitration agreement, recognizing the competence of the arbitral tribunal for the final settlement of a civil dispute, bear an increased risk of committing or not committing the necessary procedural actions, including choosing an arbitrator. The decision, made by the arbitrage has the property of binding on the parties, which is expressed, inter alia, in the prohibition of the subsequent revision of this decision on the merits. Due to the circumstances of the case, considered by the Supreme Arbitration Court of RF, the actions of the losing party were aimed at overcoming the final decision of the arbitration court and represented abuse of law. In turn, the Supreme Arbitration Court of the Russian Federation unreasonably denied to apply estoppel rule to the statement of the losing party of the dispute, which is also applicable in procedural legal relations

The role of the cytokines in the pathogenesis of pseudoexfoliation syndrome

<b>AIM:</b> To examine the mechanism of the development of pseudoexfoliation (PSX) syndrome via both cytokine formation and endothelial vasorelaxing and growth factors that will provide us new therapeutic insights for the treatment.<b>METHODS:</b> This is a cross sectional study included two groups; Group 1:control patients with nuclear cataract (<i>n</i>=20, aged 51-80 years). Group 2:PSX patients with nuclear cataract (<i>n</i>=18, aged 50-90 years). Patients with other ophthalmic problems and systemic diseases were excluded. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and nitrotyrosine levels were determined through serum samples by Enzyme-linked immunosorbent assay (ELISA) method. Nitrite-nitrate levels were measured with photometric endpoint determination.<b>RESULTS:</b> There were no significant differences between the groups in terms of age, VEGF, IL-1β, nitrite-nitrate and nitrotyrosine. The significant results were the mean IL-6 levels that were higher in PSX group 2 (37.68±29.52 pg/mL) compared to that in control group 1 (15.32±10.08 pg/mL) (<i>P</i><0.001).<b>CONCLUSION:</b> Several interacting and extending biochemical pathways may lead to the promotion of VEGF and IL-6 expressions. IL-6 which is the only altered marker in our study may indirectly cause an increase of vascular permeability and neovascularization. We suggest inflammation as a factor that can be involved in etiopathogenesis of PSX

Effects of Taurine and Age on Cerebellum Antioxidant Status and Oxidative Stress

Background: Aging is an inevitable biological process characterized by a general decline in various physiological functions and resistance to stress. The aim of the present study was to investigate the effects of taurine on advanced oxidation protein products, malondialdehyde, glutathione, and superoxide dismutase, in young and middle-aged rat cerebellum. Materials and methods: Middle-aged (13–14 months of age) male albino Wistar rats were divided into two groups as the middle-aged control and the middle-aged taurine groups. Young (6–7 weeks of age) male albino Wistar rats were divided into two groups as the young control and the young taurine groups. While the rats in the control groups were given 0.5 mL of isotonic sodium chloride, the others were given taurine by intraperitoneal injection at a single dose of 200 mg/kg/day for 7 days. Results: The cerebellum glutathione levels were significantly higher in the control group of young rats when compared to the control group of middle-aged rats (p<0.05). The cerebellum malondialdehyde levels were significantly lower in the taurine group of middle-aged rats when compared to the middle-aged control (p<0.05). The cerebellum glutathione levels were increased in the taurine group of middle-aged rats when compared to the middle-aged control group (p<0.05). The cerebellum malondialdehyde levels were significantly lower in the young taurine group when compared to the young control (p<0.05). Conclusion: In conclusion, the results of the present study suggest that exogenous taurine can prevent the increased production of age-related lipid peroxidation products and might have a potential role for the retardation of age-related oxidative events