223 research outputs found
Evaluation of the toxicity of onyx compared with n-butyl 2-cyanoacrylate in the subarachnoid space of a rabbit model: an experimental research
No full textATILLA, PERGIN/0000-0001-5132-0002The toxic effects of onyx, its solvent dimethyl sulphoxide (DMSO), and n-butyl 2-cyanoacrylate (NBCA) were evaluated after infusion into the subaracnoid space of a rabbit model. Each of the two various concentrations of onyx, pure DMSO, NBCA, and normal saline solution were percutaneously infused into the pontocerebellar cisternae of 39 domestic male albino rabbits, after which, the brain stems and medial cerebellar tissues were harvested for biochemical and histopathological studies. The specimens infused in various concentration of onyx, DMSO, and NBCA showed neural tissue necrosis and edema with inflammatory cell infitration in the acute stage. Although the mean values of the lipid peroxidase in the control, saline, and NBCA groups were found to be almost similar, they were found to be low in the onyx and DMSO groups. This experimental study suggests that NBCA, and various concentrations of onyx and DMSO have toxic effects on the neural tissues of rabbits when infused into the subarachnoid space
Parkinson Hastalığı Hücresel Modelinde İnflamasyonun ve İnflamasyon Sonrası Uygulanan N-Asetilsisteinin H4 Hücrelerindeki Lag3 ve Tlr2 Reseptörleri Üzerine Etkisi
No full textKaya, Z.B., The Effect of Inflammation and Post-Inflammatory Administration of N-Acetylcysteine on LAG3 and TLR2 Receptors on H4 Cells in the Cellular (In Vitro) Model of Parkinson's Disease, Hacettepe University Graduate School of Health Sciences, Histology and Embryology Program Doctor of Philosophy Thesis, Ankara, 2021. Parkinson's disease is a complex, multifactorial neurodegenerative disease that has prevalence of 1% over the age of 55. Pathological hallmarks of Parkinson's disease include the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of inclusion bodies that contain predominantly alpha-synuclein (α-syn) and ubiquitinated proteins, called Lewy bodies. Although the formation of α-syn occurs intracellular, it can also be translocalized to extracellular space and then taken into the other cells via receptor mediated endocytosis. TLR2 is a well known receptor which detects extracellular α-syn and modulates the uptake of the protein by other cells. Uptaken α-syn is known to trigger expression and secretion of inflammatory cytokines such as TNF-α, IL-1β, IL-2 and IL-6 and induce neuroinflammation, apoptosis and mitophagy that results in cellular death. N-Acetylcysteine (NAC), an anti-inflammatory and anti-carcinogenic drug, has gained some focus to circumvent the detrimental effects of neuroinflammatory response. In this thesis, we hypothesized that, NAC treatment will result in anti-inflammatory response that restrict in vitro apoptotic and neuroinflammatory response by modulating transcription and expression of TLR2 and LAG3 receptors. In order to test this hypothesis, WT α-syn overexpressing human neuroglioma (H4) cell line was treated with TNF-α to induce inflammation and NAC, as anti-inflammatory drug to recover from deleterious effects of TNF-α induced inflammation and apoptosis. α-syn protein transcription and expression were validated by q-PCR and Western Blot, respectively. Cell viability was measured by Toxilight assay, and apoptosis was evaluated by Western Blot and TUNEL methods. We observed that NAC treatment diminishes inflammation mediated toxicity and cell death by altering transcription and expression of TLR2 and LAG3 receptors. Thereby, this study demonstrates NAC to be a promising candidate to recover from neuroinflammation that occurs in Parkinson’s Disease.Kaya, Z.B., Parkinson Hastalığı Hücresel Modelinde İnflamasyonun ve İnflamasyon Sonrası Uygulanan N-Asetilsisteinin H4 Hücrelerindeki LAG3 ve TLR2 Reseptörleri Üzerine Etkisi, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü, Histoloji ve Embriyoloji Programı Doktora Tezi, Ankara, 2021. Parkinson hastalığı, bir çok sistemin etkilendiği nörodejeneratif bir hastalıktır. Hastalığın prevalansı genel popülasyonda binde 2-3, 55 yaş üzerinde ise %1 oranındadır. Parkinson hastalığındaki patolojik değişiklikler substantia nigra pars compacta'daki dopaminerjik nöronların kaybı ve hücrelerin içinde Lewy cisimciği olarak adlandırılan, ağırlıklı olarak alfa-sinüklein (α-syn) ve ubikutinlenmiş proteinler içeren küresel inklüzyon cisimciklerinin saptanması şeklindedir. α-syn proteinin nöronlarda hatalı katlanmalar sonucu hücre içinde çeşitli yerlerde birikebildiği gibi hücre dışı alana da geçebildiği bilinmektedir. Hücre dışı alana geçen α-syn proteini özellikle nöronlar ve glia hücreleri tarafından hücre içine endositoz yolu ile alınır. Endositozda TLR2 ve LAG3 reseptörlerinin rolünün açıklanabilmesi için çeşitli çalışmalar yapılmaktadır. α-syn proteininin endositozu, TNF-α, IL-1β, IL-2 ve IL-6 başta olmak üzere çeşitli inflamatuar sitokinlerin üretimine ve salınmasına sebep olmanın yanı sıra; hücre içinde mitokondriyal yolak üzerinden apoptoz ve mitofajiyi tetikleyerek hücre ölümünü yol açmaktadır. N-Asetilsistein (NAC), anti-oksidan, anti-inflamatuar ve anti-kanserojen etkilere sahip bir ilaçtır. Bu tez çalışmasında, inflamasyonun tetiklenmesi sonrası, LAG3 ve TLR2 reseptörlerinin ekspresyonunda artış görülebileceği ve inflamasyon NAC ile kontrol altına alındığında, inflamasyonun sebep olduğu hasarın azalması ve hücre canlılığında artış görülebileceği hipotezlerinde bulunuldu. Bu varsayımları test etmek amacı ile; in vitro koşullarda deney ve kontrol grupları içeren bir çalışma planlandı. α-syn proteinini aşırı eksprese eden insan nöroglioma (H4) hücre hattı kullanılarak inflamatuar bir Parkinson hastalığı modeli oluşturuldu. İnflamasyon, TNF-α ile tetiklendi ve NAC uygulanarak inflamasyon kontrol altına alındı. Çalışmada α-syn protein ekspresyonu ve transkripsiyonu, Western Blot ve q-PCR metotları ile ölçüldü. Hücre canlılığı Toxilight testi ile, apoptoz Western Blot tekniği ile apoptoz belirteçlerinin ölçülmesi ve TUNEL immunofloresan işaretleme metodu ile değerlendirildi. TLR2 ve LAG3 reseptörlerinin transkripsiyonları q-PCR metodu ile ölçüldü. Reseptörlerin protein düzeyleri immunofloresan işaretleme ve Western Blot tekniği ile saptandı. Elde edilen veriler ışığında, NAC tedavisinin, TLR2 ve LAG3 reseptörlerinin transkripsiyonunu ve ekspresyonunu değiştirerek inflamasyon aracılı toksisiteyi ve hücre ölümünü azalttığı belirlendi. Bu çalışma ile, NAC'nin Parkinson Hastalığında ortaya çıkan nöroinflamasyon süreci için umut vaat eden bir aday olduğu düşünüldü
Otoimmun ve Vasküler Hastalıklarda Erken Dönemde Endometriyum Reseptivitesinin Değerlendirilmesi
No full textAt each monthly cyle, endometrium undergoes structural changes and renews itself under hormonal control. A healthy endometrium is necessary for a succesful implantation and pregnancy.
Implantation depends on the interaction between the blastocyst and endometrium. During this interaction many molecules such as cytokins [ Leukemia İnhibitory Factor (LIF), Colony-Stimulating Factor-1 (CSF-1), IL-1], growth factors and adhesion molecules (integrins) play important roles. These molecules are controlled by estrogen and progesterone and are synthesized by the endometrium at certain phases of the menstrual cycle and early pregnancy. During the interaction of the blastocyst with the endometrium, different types of ‘cell death’ processes are observed in endometrial epithelial cells and stromal cells. Autophagy is one of them and Beclin-1 is expressed in early autophagy. Recent studies decline the cellular sources and expression mechanisms of these factors. Patients with autoimmune diseases and MTFHR thrombophilia can have recurrent miscarriages.
The aim of this study was to investigate the expression of some of the factors which may play crucial roles in implantation in the normal pregnancies, in patients with autoimmune diseases and MTHFR mutations, and try to compare them to find out the differences which may interfere in implantation in these pregnancies.
Abortus material until 10th gestational-week are used in this study. Group 1; control group (unwanted unwanted induced abortions), Group 2; abortus materials from pregnancies with autoimmun diseases, Group 3; abortus material from pregnancies with hereditary thrombophilia (MTHFR). LIF, IGF-1 and Beclin-1 expressions are investigated immunohistochemically.
In patients with autoimmune diseases and MTHFR thrombophilia, miscarriages are common.
The explanation of the changes of these factors in autoimmune and MTHFR thrombofilia may help to contribute to understand the etiology of unsuccesfull pregnancies in these patients and may help to improve treatment protocols.Endometriyum mensturel siklus boyunca hormonal kontrol altında sürekli yenilenen ve düzenlenen bir dokudur. Gebeliğin sağlıklı bir şekilde oluşabilmesi ve tamamlanabilmesi için; sağlıklı bir endometriyum ve başarılı bir implantasyona ihtiyaç vardır.
Başarılı bir implantasyon için; blastosist ve endometriyum arasında karşılıklı bir etkileşimin olması gerekmektedir. Bu etkileşimde sitokinler [Leukemia İnhibitory Factor(LIF) , Colony-Stimulating Factor-1 (CSF-1), IL-1], büyüme faktörleri ve adezyon molekülleri [İntegrinler] rol oynamaktadır. İmplantasyonda rol alan bu moleküller östrojen ve progesteron tarafından kontrol edilmekte ve endometriyumdan mensturel siklusun belirli evrelerinde ve gebeliğin erken dönemlerinlerinde salgılanmaktadır. Blastosist ve endometrium arasındaki etkileşim sırasında endometriyal epitel ve stomal hücrelerinde farklı hücresel ölüm mekanizmaları gerçekleşmektedir. Bunlardan bir tanesi de otofajidir ve Beclin-1 otofajinin erken dönemlerinde önemli role sahiptir. Yapılan çalışmalarda implantasyonda rol alan bu faktörlerin hangi hücrelerden ve ne zaman salgılandığı gösterilmiştir. Otoimmun ve MTHFR (Metilentetrahidrofolat Redüktaz) trombofilili hastalarda erken dönemde tekrarlayan gebelik kayıpları görülmektedir.
Bu çalışmada normal, otoimmun ve MTHFR trombofilili hastalarda erken gebelik kayıplarında implantasyonda önemli rol alan bu faktörlerin nasıl değiştiği araştırıldı. Çalışmada invitro olarak ilk 10 haftada gebelik kaybı olan hastalardan elde edilen düşük materyalleri kullanıldı. 1. Grup; (kontrol grubu) sağlıklı bireylerin istenmeyen gebeliklerinden, 2. Grup; otoimmun hastalardan ve 3. Grup: MTHFR trombofilili hastalardan elde edildi. Alınan doku örneklerinde LIF, IGF-1 ve Beclin-1 immunohistokimyası yapıldı.
Otoimmun ve MTHFR trombofilili hastalarda halen başarısız gebelikler görülmektedir. İmplantasyonda rol alan faktörlerin bu hastalıklarla ilişkisinin ortaya konması başarılı gebelikler oluşması için yapılan tedavi protokollerine olumlu katkıda bulunacaktır
Comparison of the effects of 1,25 dihydroxycholecalciferol and prostaglandin E2 on orthodontic tooth movement
No full textThis study compared the effects of local administrations of prostaglandin E2 (PGE2) and 1,25-dihydroxycholecalciferol (1,25-DHCC) on orthodontic tooth movement in rats. Thirty-seven 6-week-old male Sprague-Dawley rats, weighing 160 ± 10 g were used. Five rats served as the baseline control group. A fixed appliance system exerting 20 g of distally directed force was applied on the maxillary incisors of 32 animals for 9 days. Eight rats served as the appliance control group; 8 received a 20-μL injection of dimethyl sulfoxide (solvent for 1,25-DHCC) on days 0, 3, and 6; 8 received 20 μL of 10-10 mol/L 1,25-DHCC on days 0, 3, and 6; 8 received a single injection of 0.1 mL of 0.1 μg PGE2 only on day 0. There was no significant difference in tooth movement between the PGE2 and the 1,25-DHCC groups. Both PGE2 and 1,25-DHCC enhanced the amount of tooth movement significantly when compared with the control group. The numbers of Howship's lacunae and capillaries on the pressure side were significantly greater in the PGE2 group than in the 1,25-DHCC group. On the other hand, the number of osteoblasts on the external surface of the alveolar bone on the pressure side was significantly greater in the 1,25-DHCC group than in the PGE2 group. Thus, 1,25-DHCC was found to be more effective in modulating bone turnover during orthodontic tooth movement, because its effects on bone formation and bone resorption were well balanced
On the design of low-frequency filters using CMOS OTAs operating in the subthreshold
No full textDesign considerations on a circuit technique based on subthreshold operation of MOS transistors is described for the realization of low-frequency OTA-C active filters with small capacitance values of the order of 25-400 pF. The circuit technique described is applied to the beta@(13-40 Hz), delta@(1-4 Hz) band filters for EEG signals. Because of small capacitance values the filter circuit is suitable for realization on a single VLSI chip using the CMOS technology, and enables the user to implement the circuit on implantable biotelemetric applications. (Author abstract
Implications of site specific response analysis
No full textDefinition of design earthquake characteristics, more specifically uniform hazard acceleration response spectrum, on the ground surface is the primary component for performance based design of structures and assessment of seismic vulnerabilities in urban environments. The adopted approach for this purpose requires a probabilistic local seismic hazard assessment, definition of representative site profiles down to the engineering bedrock, and 1D or 2D equivalent or nonlinear, total or effective stress site response analyses depending on the complexity and importance of the structures to be built. Thus, a site-specific response analysis starts with the probabilistic estimation of regional seismicity and earthquake source characteristics, soil stratification, engineering properties of encountered soil layers in the soil profile. The local seismic hazard analysis would yield probabilistic uniform hazard acceleration response spectrum on the bedrock outcrop. Thus, site specific response analyses also need to produce a probabilistic uniform hazard acceleration response spectrum on the ground surface. A general review will be presented based on the previous studies conducted by the author and his co-workers in comparison to major observations and methodologies to demonstrate the implications of site-specific response analysis
Effect of increased intra-abdominal pressure on urinary system development in fetal rabbits
No full textAim: To investigate the effect of increased intra-abdominal pressure (IAP) on the fetal urinary system
THE EFFECT OF NU-SERUM OR FBS CONTAINING CULTURE MEDIA ON SH-SY5Y HUMAN NEUROBLASTOMA CELL LINE
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