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Normal akci̇ğer bronşi̇al epi̇telyum hücresi ile kistik fibrozis (KF) akciğer bronşial epi̇telyum hücresi̇ne farkli grup anti̇bi̇yoti̇kleri̇n hücre i̇çi̇ne gi̇ri̇şleri̇ arasindaki̇ farkin beli̇rlenmesi̇

2017
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Advisor: Prof. Dr. Ferda Akar ; Prof. Dr. Sarhan Sakarya

Abstract (EN)

Although the respiratory system has an open gate to the environment, when compared with other sytems, healthy human does not have a respiratory infection frequently. The most important protective component of the respiratory system is the mucociliary construction. This structure protects the system by preventing the approach of microorganisms as well as other particles. The volume of periciliary liquid decreases at patients suffering from cyctis fibrosis due to the mutation at Cystic Fibrosis Transmembrane Conductance Regulator gene. The mucus of lung can not be cleared due to this disruption. This dehydration in mucus leads a tight adhesion to the glycocalyx construction. All these alterations lead to form a proper environment in respiratory system for colonization of bacteries such as P. aeruginosa. We aimed to investigate in the cells which doses can be achieved at what time points in order to obtain the effective concentrations of antibiotics having different mechanism of effect at normal lung bronchial epithelium cells and lung epithelium cell in cystic fibrosis patient known to have a problem at intracellular cell material transfer. We used definite doses of vancomycin which disrupts cell synthesis and tigecyclin which is the first member of semisynthetic analogs glycilcyclin that disrupts protein synthesis for determining bronchial epithelium cell of cystic fibrosis patients and bronchial epithelium cell of normal lung penetration dose response and time response at cell culture studies and the diferences in cell culture due to dose and time was determined by high performance liquid chromatography (HPLC). When the cell penetration ratio was compared for IB3-1 cells and normal cells with 10, 30, 100 ve 300 µg/ml doses of Tigecyclin, it was found significantly higher for IB3-1 cells. While the cell penetration ratio of antibiotics for cyctic fibrocis cells was found as 22.43% for 3 µg/ml dose, 25.79% for 10 µg/ml dose, 36.20% for 30 µg/ml dose, 33.09% for 100 µg/ml dose and 18.30% for 300 µg/ml dose, it was found as 24.62% for 3 µg/ml dose, 8.28% for 10 µg/ml, 4.57% for 30 µg/ml dose, 2.65% for 100 µg/ml dose and 2.71% for 300 µg/ml dose for normal broncial epitelium cells. When the cell penetration amounts was compared with the given amounts, it was found very near to 30 µl/ml MİK value and this dose was found as the optimal dose for cell penetration. For dose-time studies for Tigecyclin 30 µg/ml dose performed with IB3-1 and BEAS cells, the cell penetration amount was found significant at 1 h, 2 h, 4 h, 8 h,16 h, 24 h for IB3-1 cells. While the cell penertaion ratio was observed as 12.57% for 1 h, 23.20% for 2 h, 33.23% for 4 h, 45.85% for 8 h, 45.29% for 16 h and 39.60% for 24 h for cyctic fibrosis cells, it was observed as 3.64% for 1 h, 4.33% for 2 h, 7.51% for 4 h, 9.43% for 8 h, 6.55% for 16 h and 4.30% for 24 h for normal broncial epitelium cells. The best cell penetration ratio was observed at 8 h for IB3-1 cells. For the dose studies of Vancomycin, the cell penetration amount in the cell was given to be highly above MİK value determined in the standarts (CLSI ve EUCAST) and the cell penetration amount was determined to be highly below MİK value (the permeble amount was determined for IB3-1 cells as 0,88% and for BEAS cells as 1,26% for only 300 µg/ml doses each). Consequently, the cell penetration of tigecyclin into cystic fibrosis lung cell was found higher than normal lung cell. For 30 µg/ml MIC optimal cell penetration dose, the cell penetration of tigecyclin was found significant into cystic fibrosis lung cell and normal lung cell for dose time study at 1, 2, 4, 8, 16 ve 24 hours. The best and higher penetration into cystic fibrosis lung cell was obtained at 8th hour. The cell penetration of vancomycin into cystic fibrosis and nomal bronchial cell was observed too little and insignificant. Due to that the dose response study was not performed for vancomycin. Therefore, the cell penetration of tigecyclin was found higher than vancomycin at cystic fibrosis epithelium cell and normal lung epithelium cell.

Author

Necati Günay

How to Cite

Necati Günay (Master Thesis). Normal akci̇ğer bronşi̇al epi̇telyum hücresi ile kistik fibrozis (KF) akciğer bronşial epi̇telyum hücresi̇ne farkli grup anti̇bi̇yoti̇kleri̇n hücre i̇çi̇ne gi̇ri̇şleri̇ arasindaki̇ farkin beli̇rlenmesi̇, 2017, Aydın Adnan Menderes University.

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