Hydorxyl photolinker1/28/2024 The main limitation of the use of this enzyme is its high liability in physiological environment collagenase loses its activity in less than 24 h at physiological conditions. Since fibrotic lesions are produced in ECM, local administration of CCH promote a meaningful reduction of the excessive collagen fibers present in fibrotic tissues, alleviating thereby the painful symptoms of these diseases. Type I and III are the major collagen fibers in ECM, while type IV are mainly present in basement membranes. CCH is a matrix metalloproteinase that specifically cleaves type I and III fibrillar collagens without affecting type IV collagen. Since Food and Drug Administration (FDA) approved in 2010 the injection of Collagenase Clostridium Histolyticum (CCH) for the intra-lesional treatment of Peyronie’s disease and Dupuytren’s contracture, collagenase has become the preferred treatment for these localized pathologies. Furthermore, several side effects as tendon, nerve, or artery injuries are commonly found. Restoration of a proper functionality is challenging, and relapses are not rare. Surgical procedures are invasive interventions that frequently involve long recovery times for patients. These diseases are mainly treated by surgery or collagenase administration. These pathologies are characterized by an overproduction of collagen, which induces local discomfort and functional limitation to the patients. This process is observable in different fibrotic-type diseases, such as scleroderma (morphea), and those with localized fibrotic lesions that frequently cause severe local dysfunction (i.e., painful erections in Peyronie disease or hand contractures in Dupuytren disease ). This can also be observed in pathological wound healing, leading to abnormal, hypertrophic or keloid scars, as consequence of autoimmune conditions. The process may occur systemically (i.e., systemic sclerosis ) or locally (i.e., liver cirrhosis ) as an abnormal repairing process following inflammatory lesions. The inappropriate remodeling of ECM lead to the formation of fibrotic lesions fibrosis, which are characterized by scarring and thickening of the affected tissue. This overproduction leads, in turn, to the accumulation of excessive amounts of collagens, and the contraction and remodeling of the connective tissue. These cells are ultimately responsible for the overproduction of ECM-related proteins. Collagen is synthesized by fibroblasts and other mesenchymal cells, such as myofibroblasts. This pathology usually leads to discomfort and malfunction or disablement of the affected organ. Fibrosis is defined as the excessive overproduction and accumulation of collagens and other extracellular matrix (ECM) proteins in the connective tissue of different organs.
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