Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of new therapies for treatment of chronic wounds has not matched the availability of treatment modalities forecast by the pharmaceutical industry. This is attributable in large part to difficulties encountered in clinical trials as well as in isolating study design variables. Our hypothesis attempts to address this shortcoming. We are proposing that chronic wound pathogenesis is based on 3 fundamental factors: the cellular and systemic changes of aging, repeated ischemia-reperfusion injury, and bacterial colonization with resulting inflammatory host response. The derivation of this hypothesis is founded on the observation that the 3 primary categories of chronic wounds--pressure ulcers, diabetic ulcers, and venous ulcers, which are the overwhelming majority of chronic wounds--have these common causative factors. Our hypothesis incorporates major implications for treatment modalities based on these factors. Addressing the first issue, the cellular and systemic changes of aging, Regranex (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a platelet-derived growth factor drug, has shown great promise. Additional treatment modalities that address the second and third problems, repeated ischemia-reperfusion injury and bacterial colonization, include vacuum-assisted closure, warming of local tissue, and water irrigation using pulsed lavage. Additionally, treatment comprising a combination of these approaches has demonstrated success.
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PMID:Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. 1514 94

Becaplermine gel (Regranex) is an hydrogel which contains 100 microg of Platelet Derived Growth Factor-BB (rhPDGF-BB) per gram. Regranex is presented in 15-gram multidose tubes. It has been approved as adjuvant treatment for neuropathic diabetic ulcerations of less than 5 cm2, extending into the subcutaneous tIssue, in the absence of ischemia, in conjunction with a standardised program of appropriate wound care, (control of infection, sharp debridement, provision of a moist environment and avoidance of pressure on the wound). PDGF-BB promotes cutaneous wound healing by increasing proliferation and migration of dermal fibroblasts and extracellular matrix deposition. PDGF also promotes chemotaxis of neutrophils, monocytes and smooth muscle cells in wounds. Topical application of rhPDGF-BB speeds wound healing and promotes granulation tIssue formation, synthesis of extracellular matrix and the inflammatory phase of the wound healing process in healthy and healing-impaired animal models. In clinical trials in humans, accelarated healing has been demonstrated in patients with lower extremity diabetic neuropathic ulcers and decubitus sores by increasing granulation tIssue formation and epithelialization. Local toxicity studies in humans were negative (repeated becaplermin gel application under occlusion to intact or abraded skin, dermal sensitization tests). Pharmacokinetic studies in humans have shown that systemic absorption after topical applications was minimal. In trials, systemic and local tolerance were excellent. Reported adverse effects were similar in incidence and in nature in all groups. The 0.01% Regranex gel is safe and easy to use, with single daily application. It is currently the only commercially available topical growth factor for use in cutaneous wound healing.
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PMID:[Becaplermin gel (Regranex gel)]. 1525 9

Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery.
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PMID:Becaplermin gel in the treatment of diabetic neuropathic foot ulcers. 1868 46