From Skin & Allergy News
Topical PAI-2 Seems to Improve Healing of
Venous Ulcers
David R. Branch, Contributing Writer
[Skin & Allergy News 30(3):36, 1999. ¸ 1999 International Medical News
Group.]
Orlando, Fla. -- Suppression of plasminogen activators in chronic venous leg ulcers
appears to improve healing of these wounds and may open up opportunities for
effective topical therapy.
This was the finding of an Australian pilot study reported at a meeting on wound
healing sponsored by International Business Communications.
Plasminogen activator inhibitor 2 (PAI-2) suppresses the activity of urinary
plasminogen activator (uPA) and, to a lesser extent, tissue plasminogen activator
(tPA) in wound fluid.
Topical application of PAI-2 was associated with healing of venous ulcers in a
double-blind, placebo-controlled trial of 20 patients, C. L. Bunn, Ph.D., said in a
poster presentation at the meeting.
The median ulcer area in 11 patients who received the active drug was reduced by
24% over 29 days, compared with a slight increase in median ulcer area among nine
placebo patients, said Dr. Bunn of Biotech Australia, Roseville, New South Wales.
In the trial, PAI-2 or the placebo was applied to the ulcers once daily for 5
consecutive days. All patients received standard four-layer compression bandaging.
Wound area was determined by tracing at days 1, 5, 15, 22, and 29.
Levels of uPA activity -- which has been associated in previous studies with
increased proteolysis in wound beds -- were measured at 2 hours after treatment, 4
hours, 6 hours, and on days 2, 3, 4, 5, and 29.
There was a significant decrease in uPA activity during the first 6 hours after
administration of PAI-2, but it returned to pretreatment levels after 24 hours,
despite continued daily application of the topical agent, Dr. Bunn noted.
There were no adverse events related to trial medication.
The clinical trial was carried out at Fremantle Hospital, Western Australia, under the
direction of Dr. Michael C. Stacey of the department of surgery. Based on the
results of this small pilot study, a larger clinical trial is now underway.
It was originally believed that PAI-2 occurred mainly in the placenta and in the
monocyte/macrophage cell lineage, but recent studies have shown that it appears in
significant amounts in skin, gingival crevicular fluid, fibroblasts, mesothelial cells, and
vascular smooth muscle.
It appears to protect against excessive proteolysis, especially in the presence of
inflammation; stabilize the extracellular matrix and stratum corneum; and prevent
apoptosis, Dr. Bunn said.
Comparison of biologic activity in wound fluids in patients with venous leg ulceration
and in those with acute wounds suggests that the former represents a persistent
inflammatory state. |
