Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin ulceration is a cutaneous manifestation of the antiphospholipid syndrome (APS) and is associated with thrombosis of small dermal vessels. Numerous therapeutic agents have been used but are often ineffective. We describe the efficacy of heparin and fibrinolytic agents [urokinase and tissue plasminogen activator (tPA)] in the treatment of longstanding nonhealing cutaneous ulcers. In one patient, heparin plus low dose tPA resulted in healing. In another patient, treatment first with urokinase and heparin, and subsequently with tPA alone, resulted in healing. When the ulcer recurred secondary to severe peripheral edema, tPA plus heparin led to complete resolution of the ulcer. This suggests that fibrinolytic therapy and/or heparin may be useful in other recurrent thrombotic manifestations of the APS as well. However, it must be emphatically stressed that since life threatening adverse reactions can occur secondary to hemorrhage, this treatment should be undertaken only after extensive evaluation and close monitoring of the coagulation status.
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PMID:Systemic therapy with fibrinolytic agents and heparin for recalcitrant nonhealing cutaneous ulcer in the antiphospholipid syndrome. 786 28

A 4-month randomized placebo controlled trial on urokinase therapy in 36 consecutive systemic sclerosis patients randomly treated with urokinase or placebo was conducted. While patients on placebo did not show any significant improvement, in those following urokinase therapy there was a noticeable improvement in skin sclerosis observed via hand-print and ultrasonography of the skin. Vascular involvement improved: this was demonstrated by capillaroscopy results, showing an improvement in pattern and signs of revascularization and the resolution of skin ulcers. Vascular damage is a typical occurrence in systemic sclerosis cases and various vasoactive drugs are used symptoms for some such as Raynaud's syndrome or skin ulcers. At the moment these drugs seem to constitute the most effective therapy, and have few side effects. We have found only one previous study utilizing urokinase therapy for acute digital ischemia in systemic sclerosis. Our study is the first in which urokinase therapy has been used for the treatment of systemic sclerosis in a large number of patients.
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PMID:A placebo-controlled study on urokinase therapy in systemic sclerosis. 895 56

The present investigation was undertaken to explore the ulcer healing properties of three dosage schedules of various concentrations of topically administered amiloride solution in mechanically produced skin ulcers in albino rats. Four skin ulcers (two on either side of the midline) were made 2.5 cm apart on the preshaved back of each anesthetized rat with a round body skin biopsy punch (7 mm diameter) through the dermis to the depth of subcutaneous tissue. The animals were randomly divided into groups of 5 rats each. Ulcers on one side of the midline were treated with normal saline and served as control, whereas those on the other side were treated with amiloride solutions. Each ulcer was observed for its size, slough formation and any sign of irritation on alternate days until healing was complete. Healing of ulcers was significantly accelerated with all the strengths of amiloride (0.01, 0.02 and 0.04%) in all the dosage schedules (o.d., b.i.d. and q.i.d.) in terms of days required for complete healing, ulcer size and area under the size-time curve. This acceleration was dose-dependent with maximum effect at b.i.d. administration of 0.04% solution. No irritation or suppression of immunity was noticeable. Thus topical amiloride may prove to be an inexpensive and better ulcer healing agent with no apparent side effects. Inhibition of u-PA by amiloride seems to be responsible for this effect.
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PMID:Topical amiloride solution accelerates healing of mechanical skin ulcers in albino rats. 1129 8

The present investigation was undertaken to explore the ulcer-healing property of 1% amiloride ointment on mechanically produced skin ulcers in albino rabbits and at donor site of patients requiring split skin graft. Four skin ulcers measuring 2 X 2 cm(2) (two on either side of the midline) were made 2 cm apart on the pre-shaved back of each anesthetized rabbit up to the depth of subcutaneous tissue. Ulcers on one side of the midline were treated with sterile soft paraffin and served as control, whereas those on the other side were treated with amiloride ointment. Each ulcer was observed for its size, slough formation, and any sign of irritation on alternate days, until healing was complete. Healing of ulcers was significantly (p<0.001) accelerated with amiloride ointment in terms of days required for complete healing, ulcer size, and area under the size-time curve. In each patient, the anterior thigh was used as donor site. Grafts were harvested from midline using Watson's modification of Humby's knife. Each site was divided into proximal and distal halves and was covered with either soft paraffin tulle serving as control or 1% amiloride tulle as test site and then dressed conventionally. Healing was evaluated visually on 10th postoperative day. Healing was significantly accelerated by amiloride tulle in terms of days required for complete healing (p<0.01), better quality of skin regenerated, leading to ease of removal of dressing with less of patient's discomfort, and hence more acceptability (p<0.01). No irritation or suppression of immunity was noticeable. Thus, topical amiloride may prove to be an inexpensive and better ulcer-healing agent with no apparent side effect. Inhibition of urokinase-type plasminogen activator and modulation of field strengths by amiloride seem to be responsible for this effect.
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PMID:Topical amiloride ointment accelerates healing of mechanical skin ulcers in albino rabbits and patients. 1663 20