Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 µg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 µg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 µg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells.

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified.

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK-. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK- and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK-, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated.

Genotoxic effects of some l-[(benzofuran-2-yl)-phenylmethyl]-imidazoles on MCF-7 cell line.

Increased exposure to estrogen has been associated with the risk of breast cancer. Substituted benzofuran derivatives with inhibitory effects on estrogen synthesis could be considered as a potential approach to reduce the risk of breast cancer. The study of cytotoxic effects of these compounds has suggested involvement of other mechanisms such as DNA damage. In the current study we have investigated genotoxic effects of some benzofuran derivatives on MCF-7 cell line. The MCF-7 cell line was exposed both to benzofuran phenylmethyl imidazole and its 4- fluoro, 4-chloro, 2-methoxy and 2-methyl derivatives for 2 h. The Comet assay was used to examine DNA damage due to this exposure. We also studied the DNA repair capacity after 2 h exposure to genotoxic concentrations of these compounds and their recovery were evaluated after 17 and 24 h, using the comet assay. The results indicated that genotoxic effects of these compounds appeared in concentrations of 10(-8) to 10(-6) M. The 4- fluoro and 4-chloro derivatives exhibited the highest genotoxicity and the unsubstituted benzofuran phenylmethyl imidazole had the lowest effect. The 4- fluoro, 4-chloro and 2-methyl derivatives were recovered after 24 h while 2-methoxy and the unsubstituted derivatives were recovered after 17 h. The results showed that these compounds are genotoxic and the concentration of tested benzofuran derivatives with genotoxic effects are not close to their enzyme inhibitory concentration. Moreover, our study shows that the DNA damages are repairable. Therefore, it seems that the investigated compounds have the potentials as therapeutic agents.

Financial performance of the teaching pharmacies in Isfahan: an economic evaluation.

Teaching pharmacies are amongst the important cornerstones of a healthcare system for drug supplying, pharmacy education and pharmacy practice research. Assessment of the Iranian healthcare system costs shows that after personnel charges, drug outlay is the second expensive factor. This great financial mass requires integral audit and management in order to provide costumers satisfaction in addition to financial viability. Teaching pharmacies are required to realize financial viability as well as providing several educational and drug servicing goals, which makes microeconomic analysis important. The aim of this study was to evaluate the financial performance of the teaching pharmacies affiliated with the Isfahan University of Medical Sciences (with the abrreviated names as: SHM, ISJ, AZH for the confidentialiy of the financial data). This is a descriptive and cross-sectional study done in 2008. The target pharmacies of this study were all the 3 teaching pharmacies affiliated with the Isfahan University of Medical Sciences. The data collecting template was prepared using the standard scientific methods according to the goals of this research The goals also nominated necessary items needed in economic profit evaluation. The data collection template was completed by reference to the teaching pharmacies financial documents and reports, used as a base for calculating the total income and the total costs in 2007-2008 financial year. The difference between these two balances showed the value of profits or loss. The profit/cost ratio was also calculated, using the proportion of the total income to the total costs. The collected data was statistically analyzed using the Excel software (Microsoft 2007). For the financial year 2007-2008, the difference between the total income and the total costs was -831.6 million Rials (excess costs to income) for the SHM pharmacy, + 25.4 billion Rials for the ISJ pharmacy and -429.5 million Rials for the AZH pharmacy. According to our findings there is a strong requirement to improve the financial performance of all the three teaching pharmacies while maintaining a high standardard of teaching and educational affairs.