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Erdoğar Nazlı,Akkın Safiye,Nielsen Thorbjorn T.,Özçelebi Esin,Erdoğdu Batuhan,Nemutlu Emirhan,İskit Alper B.,Bilensoy Erem 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.3
Purpose Aprepitant (APRT), a selective neurokinin 1 antagonist, is clinically used in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. The low solubility of APRT, which limits its oral bioavailability, is overcome by nanonization. This study aimed to design and evaluate novel in vitro and in vivo chitosan (CS)–polyethylene glycol (PEG)-coated cyclodextrin (CD) nanoparticles and nanocapsules to enhance the solubility and oral bioavailability of APRT. Methods A novel amphiphilic CD derivative with alkyl chains of 9 carbons (ACD-C9) was synthesized to form nanoparticles and nanocapsules by using nanoprecipitation. The nanocarriers were coated with the CS–PEG conjugate to increase their biological interaction with cell membranes via the positive charge and penetration-enhancer properties of CS. The nanosystems were evaluated for particle size, surface charge, drug loading, imaging, release, cell culture, and oral bioavailability in an animal model. Results The CS–PEG-coated nanosystems had particle size of 400–550 nm, a narrow polydispersity index, positive zeta potential, and favorable drug loading (55 and 93% for nanoparticles and nanocapsules, respectively). Sustained release was observed within 24 h. Blank nanoparticles and nanocapsules were non-cytotoxic against the L929 cell line. The intestinal permeability of the nanocarriers was 2–threefold (2-3 fold) higher than that of the drug solution, and the nanocapsules afforded the highest APRT permeability through Caco-2 cells. Oral bioavailability studies in rats revealed comparable degree of drug absorption between nanocapsules and commercial APRT products. Conclusion Oral ACD-C9 nanocapsules have the potential for the treatment of chemotherapy-induced nausea and vomiting.
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Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells
Cecen, Emre,Altun, Zekiye,Ercetin, Pinar,Aktas, Safiye,Olgun, Nur Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21
Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.
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The Effect of Insulin Like Growth Factor-1 on Recovery of Facial Nerve Crush Injury
Asuman Feda Bayrak,Yuksel Olgun,Ayla Ozbakan,Safiye Aktas,Can Ahmet Kulan,Gonca Kamaci,Emine Demir,Osman Yilmaz,Levent Olgun 대한이비인후과학회 2017 Clinical and Experimental Otorhinolaryngology Vol.10 No.4
Objectives. The aim of this study is to investigate the efficacy of locally applied insulin-like growth factor 1 (IGF-1) on the recovery of facial nerve functions after crush injury in a rabbit model. Methods. The rabbits were randomly assigned into three groups. Group 1 consisted of the rabbits with crush injury alone; group 2, the animals applied saline solution onto the crushed facial nerve and group 3, IGF-1 implemented to the nerve in the same manner. Facial nerve injury was first electrophysiologically studied on 10th and 42nd days of the procedure. The damage to the facial nerves was then investigated histopathologically, after sacrification of the animals. Results. In the electrophysiological study, compound muscle action potential amplitudes of the crushed nerves in the second group were decreased. In pathological specimens of the first and second groups, the orders of axons were distorted; demyelination and proliferation of Schwann cells were observed. However, in IGF-1 treated group axonal order and myelin were preserved, and Schwann cell proliferation was close to normal (P<0.05). Conclusion. Local application of IGF-1 in a slow releasing gel was found efficacious in the recovery of the facial nerve crush injury in rabbits. IGF-1 was considered worthy of being tried in clinical studies in facial nerve injury cases.
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Properties of Synchronous Versus Metachronous Bilateral Breast Carcinoma with Long Time Follow Up
Eliyatkin, Nuket,Zengel, Baha,Yagci, Ayse,Comut, Erdem,Postaci, Hakan,Uslu, Adam,Aktas, Safiye Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12
Background: Breast cancer is the most common cancer type among women with increasing incidence rates, improved prognosis and survival. According to the localization of the tumor, breast cancer is designated as unilateral (UBC) or bilateral (BBC). BBC can be classified as synchronous (SBBC) or metachronous (MBBC) based on the time interval between the diagnosis of the first and the secondary tumors. According to the guideline of WHO 2012, BBC is generally defined as SBBC when contralateral breast carcinoma is diagnosed within 3 months. The aim of this study was to compare the characteristics and patterns of metastasis of BBC patients with UBC. Materials and Methods: A cohort of 768 patients with breast cancer treated at the Turkish Ministry of Health-Izmir Bozyaka Research and Training Hospital between 1976 and 2012 were studied. Survival analysis was performed comparing UBC and BBC patients. In addition, evaluations were performed in patients with SBBC and MBBC sub-groups. We used a 3-months interval to distinguish metachronous from synchronous. Results: When clinical and histopathological parameters were statistically evaluated, ER status, event-free and overall survival were found to be significant between UBC and BBC patients. In comparison of SBBC and MBBC patients, age, histological type of tumor, event-free and overall survival were found to be significant. Conclusions: BBC cases were found to show worse prognosis than UBC cases. Among BBC, SBBC had the worst prognosis based on overall survival rates.
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