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Information Seminar Paper

Title

A COMBINATION OF AZELAIC ACID 1.5%, MINOXIDIL 5% AND CAFFEINE 1% EFFECTIVELY IMPROVE THE SKIN FLAP SURVIVAL THROUGH REGULATION OF KATP CHANNELS AND INOS ACTIVITY

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Abstract

 INTRODUCTION: REDUCING BLOOD FLOW AND INCREASING TISSUE NECROSIS IN THE DISTAL AREAS ARE IMPORTANT CONTRIBUTORS OF THE FLAP VIABILITY WHICH ARE INDUCED THROUGH ISCHEMIA/REPERFUSION INJURY AND SUBSEQUENT CELLULAR AND MOLECULAR MECHANISMS, AND CAUSES TISSUE LOSS. THE AIM OF THE CURRENT STUDY WAS TO INVESTIGATE THE EFFECTIVENESS OF A COMBINATION OF AZELAIC ACID 1.5%, MINOXIDIL 5% AND CAFFEINE 1% IN REDUCING THE NECROTIC AREA IN SKIN FLAPS AND INVOLVED CELLULAR AND MOLECULAR INTERACTIONS.METHODS: EIGHT GROUPS OF RATS WERE SELECTED FOR ARTERY-BASED SKIN FLAP SURGERY INCLUDING CONTROL, VEHICLE, AZELAIC ACID, MINOXIDIL, CAFFEINE, COMBINATION, COMBINATION + L-NAME AND COMBINATION + GLIBENCLAMIDE. AT THE END OF THE STUDY FLAPS WERE PHOTOGRAPHED TO COMPUTE THE NECROSIS AREA. FLAP SAMPLES WERE REMOVED AND SUBJECTED TO MALONDIALDEHYDE MEASUREMENT AND WESTERN BLOT ANALYSIS FOR INOS, BCL-2, BAX AND B-ACTIN MEASUREMENT.RESULTS: ALSO, NECROTIC AREA WAS SIGNIFICANTLY LESS IN GROUPS TREATED WITH COMBINATION COMPARED TO EACH SINGLE DRUG. COMBINATION DECREASED THE EXPRESSION OF BAX AND TISSUE MALONDIALDEHYDE CONTENT AND INCREASED THE EXPRESSION OF INOS AND BCL-2 GENES, AS WELL AS THE TISSUE NITRATE CONTENT, COMPARED TO EACH SINGLE DRUG (P<0.05) AND CONTROL, VEHICLE, AND GROUPS RECEIVING L-NAME OR GLIBENCLAMIDE (P<0.01). APPLYING THE GLIBENCLAMIDE AND LNAME ABOLISHED PROTECTIVE EFFECTS OF THE COMBINATION THERAPY.CONCLUSION: COMBINATION OF AZELAIC ACID 1.5%, MINOXIDIL 5% AND CAFFEINE 1% EFFECTIVELY IMPROVE THE SKIN FLAP SURVIVAL COMPARED TO SINGLE THERAPY WITH EACH OF THESE AGENTS. IT EXERTS PROTECTIVE EFFECTS PRESUMABLY THROUGH ACTIVATION OF K-ATP CHANNELS AND INOS AND REDUCING OXIDATIVE STRESS, VASODILATION AND APOPTOSIS INHIBITION.

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