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In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, were investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Dünyada 19. yüzyıl itibari ile üretim biçimlerinde yaşanan değişim kent nüfusunun hızlı ve kontrolsüz artışı, enerji tüketiminin artışından kaynaklanan fosil yakıt tüketiminin artması, hava kirliliği, su kaynaklarının kirlenmesi, tarım alanlarının tahrip edilmesi gibi sorunlara neden olmuştur. Kentlerde yaşanan sorunların çözümüne yönelik, sürdürülebilirliği sağlamaya yönelik ilk kent modelleri 20. yüzyılın başında geliştirilmeye başlanmıştır. Geliştirilen ilk modeller sanayi devriminin yarattığı çevre kirliliklerinin çözümüne odaklanan, kırsal alanın avantajları ile kentsel alanın ekonomik avantajını sentezleyen modellerdir. İlk sürdürülebilir kent modellerini 20. yüzyılın ortalarında doğal çevreyi sürdürülebilir kılan ekolojik kent modelleri geliştirilmiştir. Son dönemde kentsel yayılmanın önlendiği, yürünebilir sokaklar oluşturulduğu, toplu taşımanın desteklenerek kirliliğin azaltıldığı, karma kullanım ile çalışma ve yaşama mekânlarının bir arada tasarlandığı kent modelleri, kent sorunlarının çözümüne yönelik olarak geliştirilmiştir. Bu dönemde öne çıkan diğer bir model ise yapı ve yerleşme ölçeğinde sürdürülebilirlik performansının değerlendirildiği sertifikasyon sistemleridir.Kentler insanların kümelendiği, çalışma alanlarının ve dinlenme alanlarının olduğu, sürekli değişim ve gelişim içinde olan mekânlardır. Ekonomik, toplumsal ve siyasal alanda gerçekleşen tüm değişimler kentlerin yapısına etki etmekte ve kentlerin dönüşmesine neden olmaktadır. Kentlerde dönüşüme neden olan önemli konular; kentin köhnemiş alanlarında ve gecekondu bölgelerinde yaşanan toplumsal sorunlar, doğal afet riski, teknik ve sosyal altyapı yetersizliği, yanlış yer seçimi ve saçaklanma ile doğal yapının tahrip olması gibi sorunlar, küreselleşme sürecinde kentin rekabet edebilirliğini arttırılması ve ekonomik olarak etkinliğini kaybetmiş kentlerin canlandırması gerekliliğidir.Üretim biçimlerinde meydana gelen değişim sonucunda gerçekleştirilen ilk kentsel dönüşüm müdahale biçimleri kentlerin sağlıklı yaşam koşullarına kavuşması amacıyla yıkılıp yeniden yapılması olmuştur. 20. yüzyılın ortalarında kentlere müdahale biçimi siyasal nedenlerin tetiklediği, kent mekânının iyileştirilmesi ve yeniden inşaat edilmesi uygulamaları olmuştur. 20. yüzyılın sonları ve 21. yüzyılın başlarında ise ekonomik nedenlerin tetiklediği dönüşüm uygulamaları gerçekleştirilmiştir. Dünya genelinde yaşanan sorunların Türkiye'de yansıması, 1950'li yıllarda yaşanan siyasal ve ekonomik dönüşümler sonucunda olmuştur. Bu dönem itibari ile Türkiye'de yaşanan sorunlar; kentsel nüfusun kontrolsüz artışı, sera gazı emisyonlarının artması ile hava kalitesinin bozulması, su kaynaklarının kontrolsüz tüketimi, elektrik ve enerji tüketiminin artışı ile enerji açığının artışı, yapay bölgelerin tarım alanlarına doğru saçaklanması ile tarımsal alanların azalışıdır. Geçtiğimiz 20 yıllık dönemde teknolojik gelişmeler ile birlikte bu sorunlara neden olan etmenler de artmaktadır.Türkiye'de yaşanan sorunların çözümüne yönelik ilk adım 1991 yılında Montreal Protokolü'ne taraf olunmasıdır. Monteral protokolünü takiben uluslararası düzlemde sera gazını azaltmaya, sürdürülebilir insan yerleşimleri oluşturmaya, iklim değişikliğine uyum sağlamaya ve ÇEDBİK aracılığı ile yeşil bina geliştirmeye yönelik taahhütler verilmiştir. Ulusal düzlemde ise ilk aşamalarda bina ölçeğinde sürdürülebilirliğin sağlanmasına yönelik yasal mevzuat geliştirilmiş, 2010 yılı itibari ile KENTGES ve 10. Kalkınma Planı gibi belgeler ile yerleşme ölçeğinde sürdürülebilirliğin sağlanmasına dikkat çekilmiştir.Türkiye'de kentsel dönüşüm uygulamaları dünyadaki örneklerinden farklı nedenler ile geliştirilmiş olup, kentsel dönüşüm süreci ilk olarak yangından ve savaştan tahrip olan kentsel alanların yeniden geliştirilmesi projeleri ile başlamıştır. Süreç, 1950 yılı itibari ile ağırlıklı olarak yasadışı konut alanlarının sağlıklaştırılması projeleri ile devam etmiş, 2000 yılı ve sonrasında özellikle afet riski nedeniyle kentsel yenileme ve sağlıklaştırma projeleri ile gelişimini sürdürmüştür.Türkiye kentsel dönüşüm süreci incelendiğinde, kentsel dönüşüm uygulamalarının genellikle kentin fiziksel sorunlarını çözmeye yönelik geliştirildikleri, çevresel kaynakların ve sosyal yapının sürdürülebilirliğinin sağlanması kaygılarını taşımadığı görülmektedir. Özellikle don dönem kentsel dönüşüm uygulamalarının sonucunda yapı yoğunluğunun artması ve sosyal dışlanmanın artması sorunları tartışılmaya başlanmıştır.Türkiye'de yerleşme ölçeğinde sürdürülebilirliğin sağlanmasında kentsel dönüşüm projeleri fırsat olarak görülmektedir. Kentsel dönüşüm ve gayrimenkul sektöründen kaynaklanan çevresel, ekonomik, sosyal ve fiziksel sorunların çözümü için, yerleşme ölçeğinde sürdürülebilirlik performansını ölçen ulusal bir sertifikanın kentsel dönüşüm projelerinde kullanılmasının faydalı olabileceği sonucuna ulaşılmıştır. Since the 19th century, the world has been facing air pollution, water resources pollution and destruction in lands for agriculture due to inevitable and fast increase in urban population as well as the increased use of fossil fuel depending on the increase of energy consumption.In order to solve these problems regarding the difficulties that urban areas faces and to maintain the sustainability, first city models were developed at the beginning of the 20th century. The initial models were focusing on solving the problems that the industrial revolution caused on environmental pollution. The aim of these models was to combine the advantages of rural areas with the economical advantages of urban areas in order to balance the sustainability. Aside from the first sustainable urban models, in the middle of the 20th Century, ecological urban models were emerged and developed in order to maintain the natural environment. Recent urban models are designed specifically to solve problems that urban areas face. To do so, the models are focused on preventing urban sprawling by building spacious streets/pavements to enable people to walk more comfortably, by supporting public transport to decrease air pollution and enabling mixed use to design both working and living areas in a combination.Another recent prominent model is certification systems that evaluate the sustainability performance within building and settlement scale. At the beginning, these certification systems were focusing on the evaluation of sustainability performance of the buildings. However, after discovering the fact that in order to maintain the sustainability of the urban areas' management, all components need to be taken into consideration, these models started to involve neighbourhoods development scales as well.Within the analysis of this thesis, LEED Neighbourhood Development Certification System, which was prepared by American Green Building Council and BREEAM Communities certification systems, which was prepared by Building Research Establishment, were evaluated. LEED Neighbourhood Development and BREEAM Communities Certification System was developed in the native land of the industrialization and to solve the problems that caused by the industrialization process as well as being frequently used in worldwide platforms. In order to measure the sustainability performance during the process, the aims that settlement scale certifications focus on are; integrated design, the choice of location and use of land, prevention of pollution, transportation system, the protection of natural resources, productivity of the water, the production of construction that achieved sustainability, and finally sustainability of social and economic structure. Both certificates have variety of strategies depending the circumstances of the countries they are being operated and developing. The points and values that are gained out of the strategies provided and implemented are determined, depending on the countries' circumstances. Urban areas locations are where people heaped together in working and resting fields, as well as being in constant change and development. All the changes occur within economical, social and political fields affect the urban areas' structure and cause urban regeneration. The important matters that cause urban regeneration are; social problems occurred in old and slum areas in the urban, risk of natural disasters, inadequacy of technical and social foundation, incorrect choice of location and damage of natural structures due to sprawl. During the period of globalisation, in order to solve these problems, the competitiveness of the city should be increased and it is needed to revive the economical structure of the urban areas.During the change on production technics, one of the first urban regeneration methods is to deconstruct the area and rebuild it, in order to enable healthier environment for the citizens for the long run. In the middle of 20th Century, due to political circumstances, the urban intervention focused on urban amendment and reconstruction the areas. However, towards the end of 20th Century and at the beginning of the 21st Century, the intervention shaped into transforming the areas instead, due to financial reasons. How worldwide issues reflected to Turkey, occurred in 1950s political and economical structure change. From that period onwards, Turkey faced problems such as; uncontrollable increase in urban population, decrease in air quality due to increase in greenhouse gas emission, uncontrolled use of water resources, electricity scarcity due to increase in energy/electricity use, decrease in agricultural lands due to sprawl of artificial areas to agricultural lands. The period of last 20 years, these factors increased depending on technological development.First step was taken in 1991 when Turkey joined Montreal Protocol, in order to solve the problems that appeared in Turkey. Due to the regulations of the Montreal Protocol Turkey signed up for a commitment regarding the decrease of worldwide use of green house gas, enabling sustainability of human settlement, adjusting to climate change and improving green buildings through CEDBIK. As for national platform, firstly legislations were developed in order to maintain the sustainability in regards to building scale. The year 2010 onwards, documents such as KENTGES and 10. Development Plan grabbed the attention to enable the sustainability in settlement scale. The urban regeneration methods in Turkey are developed differently than other worldwide examples due to circumstantial differences. The initial urban regeneration process started in order to redevelop urban areas that were damaged by fire or war. As of 1950, this process started to focus on improving illegal buildings. In 2000 and onwards, especially due to natural disaster risks, urban renewal and improvement of the projects continued to operate with development. As Turkey's urban regeneration process is examined, it can be seen that the urban regeneration was generally focus on solving and improving the physical issues of the urban areas. In other words, there was no consideration or concern of enabling the sustainability of environmental sources as social structure. Especially nowadays it is argued that as a result of urban regeneration application, there is an increase in construction volume and social isolation. In Turkey, up until 2023, urban regeneration consists of 6 to 7 million constructions yet to come. It is predicted that this process will affect around 25 million people. It is also foreseen that in order to make this project happen, 400 billion dollars will be needed for the budget. The social, environmental, financial and physical problems that Turkey's reel estate industry and urban regeneration projects caused are; as Turkey's commitment to worldwide platform is taken into consideration, it will be highlighted that urban regeneration applications should be in integrated design and sustainability principle. Therefore, urban regeneration projects in Turkey are seen as an opportunity to enable the settlement scale in sustainability. In Turkey as part of an urban regeneration, from the beginning of the project's concept process, these questions are needed to be answered; how can the social structure be protected or improved? With which sustainability methods, the communal social and physical needs can be ensured? With which ways, the environmental sustainability of the urban areas can be maintained? How can the project protect the nature life areas and how can the bio-variety be improved? How can the carbon emission consumption of the urban areas be reduced? How can the unrenewable natural resources, be prevented to be used? LEED ND and BREEAM Communities certificates come forward when it comes to Turkey's urban regeneration projects applications in terms of socioeconomic structure and the maintenance of natural environmental sustainability. The conditions for these certificates are as follows; ensuring social integration, including all communities who will be affected by the project's process, providing residences with purchasing power, providing adequate public utility, reducing vehicle traffic, renewing historical monuments that are becoming old, decreasing the use of energy consumption, protecting water resources, reducing carbon emission amount, enabling conditions which can empower the relationship between humans and the nature. It is concluded that in order to solve the environmental, financial, social and physical problems that were caused by the urban regeneration and the reel estate industry, a national certificate, which can measure the sustainability performance in settlement scale, should be used in urban regeneration projects. This solution can bring benefits to the urban areas. 197

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Some Salvia and Thymus species of Lamiaceae family come into prominence with strong antidiabetic effects. Compared to the other species, there are limited studies on antidiabetic activity of Salvia triloba (ST) and Thymus praecox subsp. skorpilii var. skorpilii (TPS). The aim of this study was to adjust the dosage and to determine the antidiabetic effects of methanol extracts of ST and TPS in streptozotocin/nicotinamide-induced diabetic rats. Type II diabetes mellitus (T2DM) was induced by a single intraperitoneal (i. p.) injection of streptozotocin (STZ) dissolved in 0.1 M cold citrate buffer (pH 4.5) at a dose of 55 mg/kg/body weight (b.w.) and nicotinamide (100 mg/kg/b.w.) was given prior to STZ injection. For adjusting dosage, oral glucose tolerance test (OGTT) was used while insulin tolerance test (ITT), OGTT, blood glucose levels and animal weights were used to evaluate the antidiabetic effects of ST and TPS. According to the OGTT, the most effective doses for ST and TPS were 200 mg/kg and 100 mg/kg, respectively. At the end of three weeks, blood glucose levels of control goup reached to 462.50 mg/dl, whereas ST and TPS-treated groups blood glucose levels decreased less than 200.00 mg/dl. In conclusion, the present study suggests that both of ST and TPS methanolic extracts may be of therapeutic benefit in diabetes and thus need to further studies.