Protein and gene delivery systems for neurodegenerative disorders: Where do we stand today?

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics

An Optimal Mixed Integer Program for Schedeling in a Hihg Mix-Low Volume Printed Wiring Board Production Company

Finding optimum schedules for High Mix Low Volume, multistage Hybrid Flow Shop (HFS) areas, is regular and hard problem. For these kinds of production areas, there are many specific Mixed Integer Programs in literature. In this thesis, another Mixed Integer Program is demonstrated for a real Printed Wiring Board Production Company with specific features: High Mix Low Volume, multistage production with parallel units, Unlimited Interstate Buffer, Allowed Lot-Splitting, Independent set-up times of each job. Objective Function of the model is minimizing sum of costs of tardy jobs and capacity increment at each stage.Çok Çeşitlilik Az hacimli üretim yapan, birden fazla üretim safhası bulunan, her safhada birden fazla paralel kaynağı olan Hibrit Akış Atölye (HAA) alanlarında optimum üretim çizelgesi yapmak gerçek hayatta rutin ve zor bir problemdir. Bu tür üretim alanlarının optimum üretim çizelgelemeleri için literatürde bir çok özel karma-tamsayı programları mevcuttur. Bu tezde ise, çok değişkenlik az hacimli üretim yapan, birden fazla safhası bulunan, her safhada paralel kaynakları bulunan, safhalar arasında bekleme zaman hacim sınırı olmayan, parti bölmeye izin veren, her işin birbirinden bağımsız kurulum süresinin olduğu gerçek bir firmanın Elektronik Kart Üretim Çizelgelemesi için geliştirilen Karma-Tamsayı Modeli yer almaktadır. Bu modelde, amaç fonksiyonu; geç kalan işlerin maliyeti ve her safhadaki kapasite artırım maliyet toplamını minimum hale getirmek olarak belirlenmiştir

Development and Radiolabeling Evaluation of 177 Lutetium-Tedizolid

Infection diseases is still one of the major health problems all around the world. Early diagnosis and differentiation of infection from other pathological conditions such as cancer and inflammation play a critical role in treating the infection in acute stages. Imaging techniques using in the infection diagnosis present some advantages such as, the ability to image the whole body, the detection of focal location and stage, and following up on infection. Although various antibiotics can be used in the treatment, there are some problems including serious side effects of antibiotics or the development of antimicrobial resistance in the clinics. In our study, tedizolid, a second-generation oxazolidinone antibiotic, was radiolabeled with 177Lu radionuclide to develop a theranostic agent against grampositive bacterial infections. The radiolabeling was performed under room conditions, and labeling efficiency and stability were evaluated by paper chromatography and HPLC. The optimum incubation period was found as 60 min to obtain high radiolabeling efficiency. Different mobile and stationary phases in paper chromatography were tested to determine the radiochemical impurities in 177Lu-TDZ solution, and ITLC-SG was found to be proper as the stationary phase. In addition, ammonium hydroxide: methanol: water, and DTPA solutions were chosen as mobile phases. In the HPLC chromatogram, two different peaks were observed depending on the retention times of the free 177Lu and 177Lu-TDZ complex. Unfortunately, over 80% purity values were not obtained in the results of radiolabeling stability analyses; therefore, the addition of a chelating agent in the radiolabeling condition was suggested to increase the stability

Radiopharmaceuticals Used in Imaging and Treatment in Nuclear Medicine

Radyofarmasötikler tanı veya tedavi amacıyla kullanılan, yapısında radyonüklid içeren aktif moleküllerdir. Günümüzde reaktör, jeneratör veya siklotron kaynaklı radyoizotoplar kullanılarak üretilen, kanser dâhil olmak üzere bazı hastalıkların tedavisinde ve birçok hastalığın teşhisinde kullanılan 100’e yakın radyofarmasötik bulunmaktadır. Bir radyofarmasötik, radyonüklid ve farmasötik kısım olmak üzere iki kısımdan oluşmaktadır. Radyofarmasötiğin hazırlanması sırasında, görüntülenmesi istenen organ içinde lokalize olan veya organın fizyolojik fonksiyonuna katılan bir ilaç (farmasötik kısım) belirlenmektedir. Seçilen farmasötik kısım uygun bir radyonüklid ile bağlanarak işaretleme işlemi ile radyofarmasötik hazırlanmaktadır. Hazırlanan radyofarmasötiğin hastaya verilmesinden sonra radyonüklidten yayılan radyasyon dedektörlerle belirlenerek bilgisayar yardımı ile görüntüye dönüştürülmektedir. Radyonüklidin organizmadaki dağılımının görüntülenmesi ile anatomik, bu dağılımın zamana göre değişikliklerinin saptanması ile de fizyolojik bilgiler elde edilmektedir. Nükleer tıpta radyofarmasötiklerin %95’i tanı, %5’i tedavi amacıyla kullanılmaktadır. Tanı amaçlı kullanılan radyofarmasötikler gama ışını yayar iken, tedavide kullanılan radyofarmasötikler beta ışını yaymaktadırlar. Nükleer tıpta kullanılan radyonüklidlerin hepsi yapay olarak üretilmektedir. Günümüzde 2.700’den fazla radyonüklid, siklotron, reaktör ve jeneratörlerde üretilmektedir. Nükleer tıpta kullanılan sintigrafik görüntüleme teknikleri; statik görüntüleme, dinamik görüntüleme, tüm vücut görüntüleme ve hibrid görüntülemedir. Nükleer tıpta kullanılan bu yöntemler dokularda meydana gelen fizyolojik değişikliklere dayandığından erken evrede özellikle kanser gibi hastalıkların teşhisine imkân vermektedir. Tümörün erken evrede, yani anatomik değişiklikler başlamadan fizyolojik düzeyde değişiklikler oluştuğu anda teşhis edilebilmesi kanserin yayılmasına fırsat kalmadan tedaviye başlanabilmesini, dolayısıyla tedavi başarısının önemli ölçüde artmasını sağlayabilmektedir. Bu tetkikler güvenli ve ağrısızdır. Bu nedenle tüm dünyada yaygın olarak kullanılmaktadır.T Radiopharmaceuticals are active molecules which containing radionuclides in the structure and used for diagnosis or treatment. Today, there are nearly 100 radiopharmaceuticals. They were prepared by using reactors, generators, or cyclotron-derived radioisotopes and used in the treatment of certain diseases, including cancer, and in the diagnosis of many diseases. the radiopharmaceuticals consist of two parts, a radionuclide and a pharmaceutical part. During the preparation of the radiopharmaceutical, a drug (pharmaceutical part) localized in the organ desired to be imaged or participating in the physiological function of the organ is identified. the selected pharmaceutical part is labeled to a suitable radionuclide to prepare the radiopharmaceutical. After the radiopharmaceutical is given to the patient, radiation emitted from the radionuclide is detected with detectors and converted into an image with the aid of a computer. Anatomical and physiological information are obtained by visualizing the distribution of the radionuclide in the organism and by determining the changes of this distribution with respect to time. Radiopharmaceuticals are used to diagnose 95% of and 5% to treat in nuclear medicine. While radiopharmaceuticals used for diagnostic purposes emit gamma rays, the radiopharmaceuticals used in the treatment emit beta radiation. More than 2700 radionuclides are artificially produced by using cyclotron, reactors and generators. Scintigraphic imaging techniques used to static-dynamic imaging, whole body imaging, and hybrid imaging. These methods, which are used in nuclear medicine, are based on the physiological changes that occur in the tissues, allowing early diagnosis of diseases such as cancer in particular. Diagnosis of the tumor in the early stage, ie, at the beginning of the anatomical changes, at the physiological level, can lead to a significant increase in the success of the treatment, without the possibility of cancer spreading. These tests are safe and painless. For this reason, it is widely used all over the world