OBJECTIVE -We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-ß1 (TGF-ß1) with wound healing rate.RESEARCH DESIGN AND METHODS -The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-ß1.RESULTS -At presentation, MMP-9 and the MMP-9 -to-TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P Ͻ 0.001). MMP-9 and the MMP-9 -to-TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (Ͼ480 pg/ml) and TGF-ß (Ͼ115 pg/ml) further improved its predictive power (area under the curve 0.94).CONCLUSIONS -These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-ß in wound fluid may help to identify ulcers at risk of poor healing.

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The assessment and management of Charcot's arthropathy has been limited by the lack of sensitive and objective assessment methods with clinical observation and radiography forming the mainstays of evaluation [1±7]. As a result, although rest and contact casting are accepted methods of treatment there is little objective data on their impact on the disease.Radionuclide scanning has been used to compare the affected foot of patients with or without Charcot's arthropathy [8]. We used two different methods of quantitative bone scanning to study the relationship between activity of Charcot's arthropathy and clinical variables over 12 months during which patients received standard treatment of rest and contact casting. Subjects and methodsSubjects. Patients (n = 17) with acute unilateral Charcot's arthropathy were treated with rest and application of contact cast and monitored by temperature measurement. In a subset AbstractAims/hypothesis. This study used two different methods of quantitative bone scanning to study the relation between activity of Charcot's arthropathy and clinical variables over 12 months. Methods. Skin temperature of affected and unaffected feet was measured at baseline and every 3 months for 12 months in 17 subjects. Eight subjects underwent a three-phase quantitative bone scan at baseline and 3 monthly for 12 months. Bone isotope uptake in a standard rectangular area over the foot and tibia was analysed by the bilateral scan method (the ratio of isotope uptake of affected and unaffected feet) and the unilateral scan method (the ratio of isotope uptake of affected foot and ipsilateral tibia). The affected foot was placed in a contact cast for an average of 8 months. Results. At presentation the affected foot was hotter than the unaffected foot but the temperature became progressively cooler over 12 months. Median isotope uptake in the affected foot was 2.1 % of the injected dose (interquartile range, IQR 1.9±3.0). In both scanning methods the ratio of uptake decreased after casting but at 12 months the affected foot still had more isotope uptake. There was a strong correlation between temperature difference and the ratio of uptake in the bilateral scan method (r = 0.90; p < 0.0001) but when using the unilateral scan method this relation was not significant (r = 0.1; p = 0.6). A strong relation existed between perfusion of the affected foot in the dynamic phase and isotope uptake in the delayed phase of the scans (r = 0.92; p < 0.0001). Conclusion/interpretation. Bone activity and skin temperature of Charcot's arthropathy can be measured quantitatively and both improve over 12 months with contact casting. There is a strong relation between perfusion and disease activity in this condition. [Diabetologia (2000) 43:481±484]

Topical propolis is a well-tolerated therapy for wound healing and this pilot in human DFU indicates for the first time that it may enhance wound closure in this setting when applied weekly. A multi-site randomized controlled of topical propolis now appears to be warranted in diabetic foot ulcers.