ABSTRACT
Background: Asthma is common chronic disease worldwide. Methylxanthines has been used in the treatment of asthma. The study was undertaken to compare two Methylxanthines theophylline and doxofylline at doses recommended and commonly used in clinical practice in Mild Bronchial Asthma Patients. Methods: Study was conducted in patients of Mild Bronchial Asthma in TB and chest disease department of a medical college hospital. It was randomized, prospective and open label. A total of 107 patients were divided in two group .Group I was administered 400 mg theophylline SR once daily and group II was administered doxofylline 400 mg twice a day orally. Spirometric variables symptom score, and adverse effects were recorded on day 0, 7 and 21 of therapy. Data were compared and analysed using SPSS version 16. Results: Results of the study showed that there was significant improvement in spirometric variables and clinical symptom score compared to pretreatment values after medication in both groups on 7th and 21st days of treatment. But there was no statistically significant difference between improvement in theophylline and doxofylline groups with respect to spirometric variables and symptom score. There was no significant difference in two groups with respect to side effects (p>0.05). Conclusions: It is concluded in Patients of mild Bronchial Asthma Theophylline and doxofylline improve the spirometric and clinical symptoms and doxofylline has no advantage over theophylline in terms of either efficacy or safety on the doses commonly used in current clinical practice.
ABSTRACT
This study investigated the inhibitory effects of curcumin on proliferation of hemato-logical malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacety-lation levels.The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay.The expression of acetylated histone-3 (H3) in Raji,HL60 and K562 cells,and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS.The results showed curcumin inhibited pro-liferation of Raji cells significantly in a time- and dose-dependent fashion,while exhibited low toxic-ity in PBMCs.Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested.In conclusion,curcumin inhibited proliferation of Raji cells selec-tively,enhanced the level of acetylated H3 in Raji,HL60,and K562 cells,which acted as a histone deacetylase inhibitor like TSA.Furthermore,up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.
ABSTRACT
PURPOSE: The ability to noninvasively track the migration of neural progenitor cells would have significant clinical and research implications. We generated stably transfected F3 human neural progenitor cells with human sodium/iodide symporter (hNIS) for noninvasively tracking F3. In this study, the expression patterns of hNIS gene in F3-NIS were examined according to the cultured time and the epigenetic modulation. MATERIALS AND METHODS: F3 human neural stem cells had been obtained from Dr. Seung U. Kim (Ajou University, Suwon, Korea). hNIS and hygromycin resistance gene were linked with IRES (Internal Ribosome Entry Site) under control of CMV promoter. This construct was transfected to F3 with Liposome. To investigate the restoration of hNIS gene expression in F3-NIS, cells were treated with demethylating agent (5-Azacytidine) and Histone deacetylase inhibitor (Trichostatin A: TSA). The expression of hNIS was measured by I-125 uptake assay and RT-PCR analysis. RESULTS: The iodide uptake of the F3-NIS was higher 12.86 times than F3 cell line. According to the cell passage number, hNIS expression in F3-NIS gradually diminished. After treatment of 5-Azacytidine and TSA with serial doses (up to 20micro M, up to 62.5nM, respectively) for 24 hours, I-125 uptake and mRNA of hNIS in F3-NIS were increased. CONCLUSION: These results suggest that hNIS transfected F3 might undergo a change in its biological characters by cell passage. Therefore, the gene expression of exogenous gene transferred human stem cell might be affected to the epigenetic modulation such as promoter methylation and Histone deacetylation and to the cell culture conditions.
Subject(s)
Humans , Azacitidine , Cell Culture Techniques , Cell Line , Epigenomics , Gene Expression , Histone Deacetylase Inhibitors , Histones , Ion Transport , Liposomes , Methylation , Neural Stem Cells , Ribosomes , RNA, Messenger , Stem Cells , TransgenesABSTRACT
Aim To investigate the cytotoxic activity of HDAC inhibitor Trichostatin A (TSA)combined with anticancer drugs targeting DNA on T24 bladder cancer cell line.Methods MTT assay was used to detect the inhibitory rate of TSA alone or combined with ADM, MMC and DDP respectively on T24 bladder cancer cell in cancer cell proliferation by administering TSA alone or combined with ADM, MMC and DDP respectively.Jin′s equation was used to evaluate the efficacy of drug combination. Results The growth inhibitory rate of TSA combined with ADM, MMC and DDP respectively was in a concentration-dependent manner. The synergism of TSA combined with MMC was most significant. When administered in lower or moderate concentration, TSA combined with ADM or DDP in lower or moderate concentration demonstrated synergic effect too.Conclusion HDAC inhibitor TSA enhances the cytotoxic activity of anticancer drugs targeting DNA on bladder cancer cells and is promising to be used in chemotherapeutic regimens for advanced bladder cancer.