Novel options for the pharmacological treatment of chronic anal fissure--role of botulin toxin

Current Clinical Pharmacology
Mariusz Madalinski, Leszek Kalinowski

Abstract

A chronic anal fissure (CAF) is commonly referred to as an ischemic ulcer. For many years it was thought that sphincteroctomy produces anal sphincter relaxation, enhances microcirculation and promotes CAF healing. The latest studies have shown that fissure healing does not appear to be dependent on reduction in mean resting anal pressure. Our description of the process of CAF healing is based on understanding the balance between nitric oxide (NO) concentration and a level of oxidative and nitroxidative stress in wounds, which is responsible for contraction of smooth muscles (also anal sphincters), endothelial/skeletal muscle cell remodelling and proliferation. Pharmacological sphincterotomy with botulinum toxin (BTX) has an effect on motor endplate but it also has an influence on nitric oxide synthase (NOS) and other agents. Hypoxia in contracted anal sphincters induces vasoconstriction, in part, by decreasing endothelial NOS expression. Clostridium botulinum C3 exoenzyme - Rho-kinase inhibitor reverses this vasoconstriction. CAF is a site where the haemostatic mechanisms are activated. Rho inactivator C3-transferase from Clostridium botulinum abolished thrombin - stimulated endothelial cell contraction. Attenuated biotransform...Continue Reading

Citations

Feb 4, 2010·International Journal of Colorectal Disease·José GilPascual Parrilla
Jul 14, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jagmohan Singh, Satish Rattan
Jan 14, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Satish Rattan, Jagmohan Singh
May 18, 2011·World Journal of Gastrointestinal Pharmacology and Therapeutics·Mariusz H Madalinski
Jun 17, 2011·International Surgery·Turker BulutDursun Bugra
Nov 28, 2013·Gastroenterology Clinics of North America·Sherief Shawki, Meagan Costedio
Dec 29, 2010·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·S Rattan, J Singh
May 29, 2014·Expert Review of Pharmacoeconomics & Outcomes Research·Giuseppe BrisindaGiorgio Maria

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