Thalictrum orientale boiss. alkaloitleri

Tez (doktora) - Anadolu ÜniversitesiAnadolu Üniversitesi, Sağlık Bilimleri Enstitüsü, Farmakognozi Anabilim DalıKayıt no: 137953T.orientale Boiss. bitkisinin Niğde:Ulukışla'dan toplanmış toprak altı ve toprak üstü kısımları ekstre edilmiş ve alkaloitler yönünden ilk kez incelemeye tabi tutulmuştur. Kromatografik yöntemlerle izole edilen ve saflaştırılan alkaloitlerden üçünün yapısı spektral yöntemlerle belirlenmiş olup iki katerner aporfin alkaloitinin yapısı miktar azlığı sebebiyle tam olarak aydınlatılamamıştır. Alkaloitlerin tümü toprak altı kısmında elde edilmiş olup, toprak üstü kısmından elde edilen alkaloitler miktarlarının azlığı sebebiyle incelenememiştir. Bu çalışma sonunda, toprak altı kısmından elde edilen üç ana alkaloit fangkinolin (bisbenzilizokinolin), fuzitin (aporfin) ve berberin (protoberberin)'dir. Bunlardan ilk iki alkaloitin Thalictrum cinsindeki varlığı ilk kez rapor edilmiştir

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association

Demonstrating a powerful scale-up strategy for Biosimilar mAb in single use systems via physicochemical and functional characterization

Biosimilars have received a remarkable attention in the recent years. Due to the heterogeneity of biosimilar mAbs, they need to be well-characterized by various orthogonal techniques in order to identify their physicochemical and functional characteristics. Characterization of the post translational modifications, especially, glycosylation is vital to define the critical quality attributes (CQAs) which affect safety, efficacy and quality of drugs. In this study, we were able to manipulate the quality of the drug by using scale-up strategies for single use systems. By using ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (MS), we were able to demonstrate physicochemical similarities between innovator and its biosimilar candidate. Even the PTM (N-terminal pyroglutamic acid formation, C-terminal lysine truncation, methionine and tryptophan oxidation, asparagine deamidation, N-glycosylation and glycation) levels of two products from 3 and 200-liter single-use bioreactors were highly similar compared to the innovator. The mass spectrometry studies showed that the scale-up strategy from 3 liter to 200 liter was successful. Deconvoluted mass spectrum for intact and reduced masses (heavy and light chain) of innovator and its biosimilar candidates from different production scales were significantly similar. Oxidation was observed to be lower in 200 liter bioreactor compared to the 3 liter. The N-glycan profiles for the major and minor glycan species were highly similar compared to the originator. Aggregation level in 200 liter was slightly lower than that of the small scale production. Mass spectrometry becomes an important tool to enhance the biosimilarity to the originator in order to decrease the clinical efforts to be able to provide affordable drugs to the patients

An unusual pregnane derivative and dibenzylbutyrolactone lignans from Centaurea sclerolepis

21st Conference on Isoprenoids -- SEP 23-29, 2005 -- Bialowieza, POLAND[Anstract Not Available

Melatonin in preservation solutions prevents ischemic injury in rat kidneys

Abstract Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63–1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h

Chlorate and Other Oxychlorine Contaminants Within the Dairy Supply Chain

The presence of chlorate in milk and dairy products can arise from the use of chlorinated water and chlorinated detergents for cleaning and sanitation of process equipment at both farm and food processor level. Chlorate and other oxychlorine species have been associated with inhibition of iodine uptake in humans and the formation of methemoglobin, with infants and young children being a high‐risk demographic. This comprehensive review of chlorate and chlorine derivatives in dairy, highlights areas of concern relative to the origin and/or introduction of chlorate within the dairy supply chain. This review also discusses the associated health concerns, regulations, and chemical behavior of chlorate and chlorine‐derived by‐products, and provides a summary of mechanisms for their detection and removal

Farklı İllerden Toplanan Su Örneklerinde NIS İnhibitörü Olan Perklorik Asit Düzeylerinin Araştırılması

Perklorik asit (ClO4¯) suda oldukça mobil ve stabil bir inorganik anyondur. Perklorik asidin kimyasal özellikleri iyoda benzerdir ve sodyum-iyot taşıyıcısının (NIS) tiroid bezine iyot taşımasını baskılar. Yetersiz iyot alımı durumunda, hassas popülasyonlarda (gebeler, bebekler, çocuklar) tiroid disfonksiyonlarına neden olabilmektedir. Daha önceki çalışmada, İstanbul, Kayseri ve Isparta'da 24-saatlik idrar örnekleri analiz edilmiş ve çalışmaya katılanların perklorik aside maruz kaldığı görülmüştür. Bu çalışmada, Ankara, Isparta, İstanbul, Kayseri ve Sakarya şehirlerinden, tüm şehirleri kapsayacak şekilde toplam 145 rastgele örnek alınarak, musluk sularında perklorik asit düzeylerini belirlemek amaçlanmıştır. Perklorik asit analizleri için HPLC-MS/MS yöntemi kullanılmıştır. Deteksiyon limiti ve kantifikasyon limiti, sırasıyla, 0.008 ve 0.026 µg/L olarak hesaplanmıştır. Analizler arası varyasyon (%CV) düşük ve orta seviyedeki örnekler için hesaplanmıştır. Buna göre 0.4 ve 2 µg/L konsantrasyonundaki kontrol örnekleri için %CV değerleri, sırasıyla, %6.72 ve %2.72 olarak hesaplanmıştır. Örneklerin %97.9'unda perklorik aside rastlanmıştır. Ölçülen perklorik asit düzeyleri <0.02 µg/L ile 3.75 µg/L arasında değişmektedir. Örneklerin ortalaması 0.17 µg/L'dir. İstanbul, Ankara, Sakarya, Kayseri ve Isparta illerindeki medyan düzeyleri, sırasıyla, 0.081, 0.081, 0.041, 0.27 ve 0.029 µg/L olarak bulunmuştur. En yüksek perklorik asit konsantrasyonu 3.75 µg/L olarak Ankara'da ölçülmüştür. Kayseri ilinde medyan 0.27 µg/L, %75 persentil 0.34 µg/L olarak ölçülmüştür. Örneklerdeki perklorik asit konsantrasyonları, EPA tarafından musluk suları için belirlenen güvenlik sınırının (15 µg/L) altında saptanmıştır. Sonuç olarak, bu şehirlerde insanların maruz kaldığı perklorik asit kaynağının sular olmadığı gözlenmiştir. Asıl kaynağın besin maddeleri olduğu düşünülmekte ve bundan sonra yapılacak araştırmaların bu yönde devam etmesi gerekmektedir