Cytotoxicity of Mycobacterium indicus pranii on Mia-Pa-Ca2 cells

Background: MIP is a cultivable, non-pathogenic organism, which shares several antigens with Mycobacterium tuberculosis and Mycobacterium leprae. It has several proposed clinical applications. However, its cytotoxic effect on pancreatic cancer has not been documented. Hence, the study was conducted to investigate MIP induced cytotoxicity on Mia-Pa-Ca2 cells. To determine the cytotoxic potential of heat killed Mycobacterium indicus pranii (MIP) on pancreatic cancer cells in vitro along with gemcitabine & 5-fluorouracil (5-FU). Mitogen-activated protein kinase (MAPK) level was also studied post MIP treatment. Methods: Cytotoxic effect of MIP, gemcitabine and 5-FU on Mia-Pa-Ca2 cells was determined. We have analyzed extent of apoptosis using flow cytometry and changes in p38 levels, c-Jun N-terminal kinases (JNK) and extracellular signal­regulated kinase (ERK) using ELISA. Results: MIP not only exhibits cell cytotoxicity in dose dependent manner, but also enhances efficacy of gemcitabine and 5-FU when used in combination. Flow cytometry analyses reveals apoptosis of Mia-Pa-Ca2 cells post MIP treatment compared to untreated cells. MAPK pathway study using ELISA shows that p38 and JNK levels are suppressed while there is no change in ERK level. Conclusion: With these results we conclude that MIP is a cytotoxic agent. Cytotoxicity is exhibited by apoptosis. Combining MIP with gemcitabine and 5-FU shows synergistic effect (AU)

Pharmacokinetics of topically applied sparfloxacin in rabbits.

PURPOSE: Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and are widely used against many of the ocular pathogens, responsible for conjunctivitis, blepharitis, corneal ulcers etc. The aim of our study was to evaluate the ocular pharmacokinetics of sparfloxacin (0.3% w/v) in the aqueous humour of rabbits. MATERIALS AND METHODS: Pharmacokinetics of topically administered sparfloxacin were determined after a single application of 50 microl topically. The aqueous humour samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 or 6 hours after instillation. High Performance Thin Layer Chromatographic method was used to analyse the drug concentration in the aqueous humour samples. RESULTS: Fifteen minutes after the instillation of 50 microl of sparfloxacin 0.3% solution, the mean concentration in aqueous humour was found to be 1.4 microg/ml, which reaches the peak level of 3.7 microg/ml after 1.3 hours. At 6 hours, the sparfloxacin aqueous levels were 0.562 microg/ml. The clinical efficacy was predicted based on the Maximum Concentration (Cmax): Minimum Inhibitory Concentration (MIC) and Area Under the Concentration-time curve (AUC):MIC ratios. CONCLUSION: The sparfloxacin levels in aqueous humour of rabbits are sufficiently high up to the 6 hours after instillation in the conjunctival sac to provide bactericidal effect against most of the ocular pathogens. Both Cmax:MIC and AUC:MIC ratios are high enough to provide bactericidal effect against most of the ocular pathogens. Sparfloxacin (0.3%) ophthalmic preparation has excellent penetration through cornea.