30 research outputs found

    Historical Presentation of State-Religion Relations in Kyrgyzstan

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    In this study, state and religion relations in Kyrgyzstan, which appeared in world scene as an independent state in 1991 will be discussed. The issue of religious education, in which these relations are more observed and cause both internal and international disputes will be subject of factual evaluation as a sub sample. The purpose and basic thesis of the study, is to present the new aspects in Kyrgyz history deriving from the religious discourse, religion based movements and organizations that we come across at current social and political developments in Kyrgyzstan. In other words, purpose is to expose historical bases of institutional and social relations of Kyrgyzstan with religion if any, and if not, disconnections with the past. Within this framework, while making this analysis, history of Central Asia which Kyrgyzstan is a part of, its inheritances from the past inside the country's current borders will be taken into account and will be evaluated in competence with ethnic, social, economic and modernization criteria. Under the light of this factual evaluation, thesis of this study will be supported and some studies which are generally approved in literature will tried to be disproved and in the final stage, problematique that includes new titles of problems will be presented systematically

    Mito-metformin protects against mitochondrial dysfunction and dopaminergic neuronal degeneration by activating upstream PKD1 signaling in cell culture and MitoPark animal models of Parkinson’s disease

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    Impaired mitochondrial function and biogenesis have strongly been implicated in the pathogenesis of Parkinson’s disease (PD). Thus, identifying the key signaling mechanisms regulating mitochondrial biogenesis is crucial to developing new treatment strategies for PD. We previously reported that protein kinase D1 (PKD1) activation protects against neuronal cell death in PD models by regulating mitochondrial biogenesis. To further harness the translational drug discovery potential of targeting PKD1-mediated neuroprotective signaling, we synthesized mito-metformin (Mito-Met), a mitochondria-targeted analog derived from conjugating the anti-diabetic drug metformin with a triphenylphosphonium functional group, and then evaluated the preclinical efficacy of Mito-Met in cell culture and MitoPark animal models of PD. Mito-Met (100–300 nM) significantly activated PKD1 phosphorylation, as well as downstream Akt and AMPKα phosphorylation, more potently than metformin, in N27 dopaminergic neuronal cells. Furthermore, treatment with Mito-Met upregulated the mRNA and protein expression of mitochondrial transcription factor A (TFAM) implying that Mito-Met can promote mitochondrial biogenesis. Interestingly, Mito-Met significantly increased mitochondrial bioenergetics capacity in N27 dopaminergic cells. Mito-Met also reduced mitochondrial fragmentation induced by the Parkinsonian neurotoxicant MPP+ in N27 cells and protected against MPP+-induced TH-positive neurite loss in primary neurons. More importantly, Mito-Met treatment (10 mg/kg, oral gavage for 8 week) significantly improved motor deficits and reduced striatal dopamine depletion in MitoPark mice. Taken together, our results demonstrate that Mito-Met possesses profound neuroprotective effects in both in vitro and in vivo models of PD, suggesting that pharmacological activation of PKD1 signaling could be a novel neuroprotective translational strategy in PD and other related neurocognitive diseases

    Determination of Physicochemical Properties and Oxidative Stability of Rice Bran Oils

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    Bu çalışmada; stabilizasyon işleminin pirinç kepeği yağının fizikokimyasal özelliklerine ve yağ asidi bileşimine etkisinin belirlenmesi amaçlanmıştır. İki farklı pirinç kepeği çeşidi (Osmancık ve Opela); mikrodalga, etüv ve mikrodalga+etüv olmak üzere 3 farklı yöntemle stabilize edilmiştir. Pirinç kepekleri toplamda dokuz farklı stabilizasyon şartında muamele edilmiştir. Mikrodalga ile stabilizasyonda 600 W 1 dk, 600 W 2 dk, 600 W 3 dk; etüv ile stabilizasyonda 80°C’de 30dk, 100°C’de 30dk, 120°C’de 30dk, etüv ve mikrodalganın birlikte kullanıldığı kombine yöntemde ise 600 W 2dk mikrodalga+80°C’de 30dk etüv; 600 W 2dk mikrodalga+100°C’de 30dk etüv ve 600 W 2dk mikrodalga+120°C’de 30dk etüv uygulaması yapılmıştır. Stabilizasyon işleminden sonra pirinç kepek yağı solvent ekstraksiyon yöntemi ile elde edilmiştir. Elde edilen pirinç kepeği yağlarına ait serbest yağ asitliği değeri, peroksit sayısı, yağ asitleri bileşimi, sterol kompozisyonu, iyot sayısı, sabunlaşma sayısı, özgül ağırlık değeri ve kırılma indisi değeri belirlenmiştir. Uygulanan stabilizasyon işlemleri sonucunda pirinç kepeği yağlarının serbest yağ asitliği, peroksit sayısı ve iyot sayısı değerlerinin azaldığı tespit edilmiştir (p0,05). Pirinç kepeği yağında en çok bulunan sterol ?-sitosterol olarak tespit edilmiştir.In this research, it was aimed to determine the effects of stabilization on some physicochemical properties and fatty acid composition of rice bran oil. The rice bran samples (Osmancık and Opela) was stabilized under three ways (microwave, drying oven and microwave + drying oven) including nine conditions (drying oven: 80°C 30 min, 100°C 30 min, 120°C 30 min; microwave : 600 W 1 min, 600 W 2 min, 600 W 3 min; microwave + drying oven: 600 W 2 min microwave - 80°C 30 min drying oven, 600 W 2 min microwave - 100°C 30 min drying oven, 600 W 2 min microwave - 120°C 30 min drying oven). The rice bran oil was obtained by solvent extraction technology. The free fatty acids content, peroxide value, iodine number, saponification number, specific gravity, refractive index, fatty acid composition and the sterol composition of rice bran oil samples were determined. The acidity, peroxide value and iodine number of the oil samples were significantly decreased with the stabilization process applied (p0,05). ?-sitosterol was detected as the main sterol in rice bran oil

    Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice

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    Aims: Parkinson\u27s disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction. Results: Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation. Innovation: The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches. Conclusion: Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048–1066

    Translational drug discovery approaches targeting the PKD1 signaling in Parkinson's disease

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    Parkinson's disease (PD) is a chronic neurodegenerative disorder that affects about 1% of people over the age of 60. PD is characterized pathologically by the progressive loss of dopaminergic neurons and the presence of Lewy bodies in the substantia nigra, dramatic depletion of dopamine in striatum, and activation of glial cells. Although the etiology of PD is not fully understood, evidence points strongly to the involvement of oxidative stress and mitochondrial dysfunction resulting from impaired mitochondrial biogenesis. Therefore, identifying cell signaling mechanisms regulating mitochondrial biogenesis is critically important to the development of new treatment strategies for PD. We have recently shown that activation of protein kinase D1 (PKD1) is neuroprotective and that positive modulation of PKD1 protects against neuronal cell death in cell culture models of PD. The goals of my Ph.D. thesis work were to understand the molecular mechanisms of PKD1-mediated neuroprotection using cell culture and animal models of PD and to test the efficacy of positive modulators of PKD1 signaling as potential neuroprotective agents in preclinical models of PD. Herein, we demonstrate for the first time that PKD1 activation positively regulates PGC-1α transcriptional activity. Overexpression of constitutively active PKD1 increased PGC-1α promoter activity, mRNA and protein expression in MN9D dopaminergic neuronal cells. Moreover, treatment of MN9D cells with rationally designed PKD1 activator peptide (AKP4T) enhanced expression of PGC-1α and other markers of mitochondrial biogenesis. Interestingly, treatment of cells with a PKD1 inhibitor (kbNB-14270) strongly suppressed mRNA expression of PGC-1α and TFAM. Importantly, AKP4T treatment protected against dopaminergic neurotoxicity in human dopaminergic neurons. Next, we adopted a rationale-based pharmacological screening approach to identify natural compounds that activate PKD1 and found that quercetin effectively activated PKD1-mediated neuroprotective signaling and promoted mitochondrial biogenesis and bioenergetics capacity in dopaminergic cells. Furthermore, quercetin protected against dopaminergic neurodegeneration by reversing striatal dopamine depletion, TH neuronal cell loss and behavioral deficits in the MitoPark transgenic mouse model of PD. Finally, we synthesized Mito-Met, a mitochondria-targeted analog of the anti-diabetic drug metformin. We demonstrate that Mito-Met induces activation of pro-survival PKD1 kinase more potently than its parent compound metformin in dopaminergic neuronal cells. Interestingly, Mito-Met stimulated mitochondrial biogenesis and bioenergetics capacity and also protected against MPP+-induced neurotoxicity. More importantly, Mito-Met treatment significantly reduced motor deficits and striatal dopamine depletion in MitoPark mice. Collectively, the research described herein provides evidence that PKD1 activation promotes mitochondrial biogenesis in dopaminergic neurons. We also show that positive modulation of PKD1 signaling affords neuroprotection against dopaminergic neurodegeneration in preclinical models of PD. Our results suggest that PKD1 is a promising druggable target that merits further preclinical investigations for the treatment of PD.</p

    Quality in turning of Inconel X-750 superalloy

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    This study has been conducted to analyse the effects of turning the Inconel X-750 superalloy, which is a member of a nickel-based superalloy family that is frequently preferred in the aerospace and nuclear energy industries in particular, under minimum quantity lubrication (MQL), cryogenic liquid nitrogen (LN2 ) and carbon dioxide gas (CO2) cooling/lubrication conditions, with different cutting speeds (V-c = 65, 95, 125 and 155 m/min) and constant feed rate (f=0.1 mm/revolution) and cutting depth (a =0.5 mm) parameters, on the processability of Inconel X-750, hence on the surface integrity. In this context, the results obtained from the tests have been comparatively examined through surface roughness, tool wear and chip formation. Comparison results show that the cryogenic carbon dioxide method has generally provided the best surface roughness and tool wear values. The MQL method has provided the best chip formation

    Comparison of Lidocaine and Atropine on Fentanyl-Induced Cough: A Randomized Controlled Study

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    Objective of the Study: Fentanyl and atropine are drugs used for analgesia during induction and for premedication, respectively. The aim of this study was to observe the effect of atropine used for premedication on cough developing in association with fentanyl use during anesthesia induction. Methods: This was a single-blind, prospective, multi-arm, parallel, randomized clinical trial involving 120 patients between ages 3 and 15 years undergoing general anesthesia. Patients were randomized into three groups: a control group (Group C), an atropine group (Group A), and a lidocaine group (Group L). Results: Incidence of cough was 45% (n = 16) in Group C, 16% (n = 6) in Group A, and 16% in Group L (n = 6) (p = 0.009). Cough was moderate in two cases in Group A and in two in Group L, and mild in all others in these groups. In Group C, cough was mild in seven cases, moderate in six, and severe in two. Conclusion: We determined that premedication with atropine suppressed the incidence and severity of fentanyl-induced cough during induction of general anesthesia. We think that, due to its antimuscarinic effect, atropine is as effective as lidocaine as a premedication

    A Rare Cause of Respiratory Distress İn Newborn: Cystic Adenomatoid Malformation

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    Amaç: Konjenital kistik adenomatoid malformasyon (CCAM), displastik ve/veya hamartamatöz akciğer dokusunun, immatür bronş ağacından anormal dallanmasıyla oluşan, nadir görülen konjenital bir akciğer anomalisidir. İnsidansı 25-30 bin gebelikte birdir ve sıklıkla erkek bebekleri etkiler. Bu vaka sunumunda nadir görülen CCAM'ın tartışılması ve hatırlatılması amaçlandı.Olgu: Yirmi sekiz yaşında anneden 37. gestasyonel haftasında vajinal doğumla 2090 gr olarak doğan bebeğin 1 ve 5. dk. Apgar değerlendirmesi sırasıyla 9 ve 10 idi. Takiplerinde hipoglisemi gelişen ve beslenememe şikayeti olan hastanın Yenidoğan Yoğun Bakım Servisi'ne yatışı yapıldı. Yatışının altıncı gününde solunum sayılarının artmaya başlaması üzerine çekilen PA akciğer filminde sol üst lobda kistik görünüm izlendi. Tomografide sol akciğerde üst lobda, inferiora hafif uzanımıda gözlenen, en büyüğünün çapı yaklaşık 1,3 cm ölçülen birbirine yakın komşulukta multipl kistik oluşumlar saptandı. Kistik oluşumların boyutları 2 cm altında olması nedeniyle CCAM tip 2 ile uyumlu olarak değerlendirildi . Sonuç: Yenidoğan döneminde etyolojisi saptanamayan solunum sıkıntısı varlığında nadir gözükse de CCAM akılda tutulmalıdır. Hayatın ilk dönemlerinde çekilen PA akciğer filmi doğal olarak değerlendirilse bile kistlerin içinde sıvı olabileceğinden tanı dışlanamaz. Kist veya kistlerin oluşturacağı etki ve klinik duruma göre cerrahi tedavinin ne zaman yapılacağına karar verilmelidir.Aim: Congenital cystic adenomatoid malformation (CCAM) is a rare congenital lung anomaly which is charecterized by an abnormal branching of dysplastic or hamartomatous lung tissue from the immature bronchial tree. Its incidence is one of 25-30 thousand gestations and CCAM most commonly affects male infants. We aim to discuss and remind the rare CCAM with a case report.Case presentation: An (male, female) infant which had delivered at 37th gestational week from twenty-eight-year-old mother following vaginal delivery, his or her weight was 2.090 kg. Apgar scores were 9 and 10 at 1st and 5th min, respectively. Because of hypoglycemia and inability to feed, newborn was admitted to Neonatal Intensive Care Unit. A cystic formation was observed at the upper lobe of left lung on Posterior Anterior lung graphy which was taken due to the increasement of respiratory rate. Multiple cystic formations were observed in the upper lobe of the left lung in computerized tomography evaluation. These cysts were close to each other, slightly lengthened to inferior region and largest cyst was measured about 1.3 cm in diameter. Because of the size of the cystic formations was less than 2 cm, this case was evaluated as type 2-CCAM. Conclusions: In the presence of undefined neonatal respiratory distress, CCAM should be considered even if it appears as a rare disease. In spite of PA chest film taken in the early stages of life is evaluated as normal, the diagnosis can not be excluded because of cysts filled with fluid. Depending on the effects and clinical situations of the cysts, time of operation should be managed

    Frequency of human papillomavirusvaccination and knowledge levels of women between 15 and 49 years: A cross-sectional study

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    Objectives: This study aimed to determine the frequency of vaccination with the human papillomavirus (HPV) vaccine among women aged 15–49 years and their knowledge levels. Methods: This cross-sectional study was conducted on female patients aged 15–49 years who applied to a rural state hospital, family medicine outpatient clinic, between December 15, 2019, and March 1, 2020. A ques- tionnaire about HPV vaccination was filled out through a face-to-face interview. Patients who did not agree to participate in the study, who had a hysterectomy, and those diagnosed with cervical malignancy or premalig- nancy were excluded. Results: The mean age of 409 female participants was 30.0±9.1 years. None of the women who participated in this study had the HPV vaccine. The number of those who heard about the HPV vaccine was 164 (40.1%). After brief information about the HPV vaccine, 269 (65.8%) participants wanted to have the HPV vaccine. Conclusion: It was determined that the frequency of HPV vaccination and the knowledge levels about the HPV vaccine are low
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