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Copenhagen, Denmark

Mirastschijski U.,Hannover Medical School | Schnabel R.,Hannover Medical School | Claes J.,Otto Von Guericke University of Magdeburg | Schneider W.,Otto Von Guericke University of Magdeburg | And 3 more authors.
Wound Repair and Regeneration | Year: 2010

The ability to regulate wound contraction is critical for wound healing as well as for pathological contractures. Matrix metalloproteinases (MMPs) have been demonstrated to be obligatory for normal wound healing. This study examined the effect that the broad-spectrum MMP inhibitor BB-94 has when applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-β1 (TGF-β1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-β1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound closure through a twofold mechanism; by blocking keratinocyte migration and thereby blocking the necessary keratinocyte-fibroblast interactions needed for myofibroblast formation and by inhibiting the activation of latent TGF-β1. © 2010 by the Wound Healing Society.

Krarup P.-M.,Bispebjerg Hospital | Eld M.,Aalborg Hospital | Heinemeier K.,Copenhagen University | Jorgensen L.N.,Bispebjerg Hospital | And 5 more authors.
International Journal of Colorectal Disease | Year: 2013

Purpose: Submucosal collagen is paramount for colonic anastomotic integrity. Matrix metalloproteinases (MMPs) mediate collagen degradation that increases the risk of wound dehiscence. Although broad-spectrum MMP inhibitors are beneficial for anastomotic strength, they can cause adverse reactions. Knowledge of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic repair. Methods: Left-sided colonic anastomoses were made in male Sprague-Dawley rats. After 3 days when biomechanical strength is lowest, MMP mRNA and protein levels were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays and gelatin zymography. The effects of the MMP-8, MMP-9 and MMP-12 synthetic inhibitor AZD3342 was also studied. Results: MMP-8, MMP-9 and MMP-12 gene and protein expression increased profoundly (p < 0.01), and MMP-13 mRNA and MMP-2 mRNA and protein modestly (p < 0.001) in the anastomoses. MMP-3 mRNA levels were not up-regulated significantly compared with adjacent uninjured colon. Increased anastomotic MMP-12 levels paralleled macrophage infiltration by immunohistochemical analyses. AZD3342 (50 mg/kg) treatment increased the anastomotic breaking strength by 29 % (p = 0.015) day 3 compared with vehicle. Improved anastomotic strength was not accompanied with alterations of type I or type III procollagen mRNA but was possibly due to inhibition of the concerted digestive action on the existent submucosal collagens by the targeted MMPs. Conclusion: The present findings justify the concept of selective MMP inhibition to enhance anastomotic strength in colon. © 2013 Springer-Verlag Berlin Heidelberg.

Palosuo T.,Finnish National Institute for Health and Welfare | Antoniadou I.,Karolinska Institutet | Gottrup F.,Copenhagen Wound Healing Center | Phillips P.,Surgical Materials Testing Laboratory
International Archives of Allergy and Immunology | Year: 2011

Many hospitals have implemented policies to restrict or ban the use of devices made of natural rubber latex (NRL) in healthcare as precautionary measures against the perceived risk of NRL allergy. Changes in glove technology, progress in measuring the specific allergenic potential of gloves and a dramatic decrease in the prevalence of NRL allergies after interventions and education prompted us to revisit the basis for justifiable glove selection policies. The published Anglophone literature from 1990 to 2010 was reviewed for original articles and reviews dealing with the barrier and performance properties of NRL and synthetic gloves and the role of glove powder. The review shows that NRL medical gloves, when compared with synthetic gloves, tend to be stronger, more flexible and better accepted by clinicians. The introduction of powder-free gloves has been associated with reductions in protein content and associated allergies. Recently, new methods to quantify clinically relevant NRL allergens have enabled the identification of gloves with low allergenic potential. The use of low-protein, low-allergenic, powder-free gloves is associated with a significant decrease in the prevalence of type I allergic reactions to NRL among healthcare workers. Given the excellent barrier properties and operating characteristics, dramatically reduced incidences of allergic reactions, availability of specific tests for selection of low-allergen gloves, competitive costs and low environmental impact, the use of NRL gloves within the hospital environment warrants reappraisal. Copyright © 2011 S. Karger AG, Basel.

Pickwell K.,Maastricht University | Siersma V.,Copenhagen University | Kars M.,Maastricht University | Apelqvist J.,Malmo University | And 14 more authors.
Diabetes Care | Year: 2015

OBJECTIVE: Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation. RESEARCH DESIGN AND METHODS: We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries. RESULTS: Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively). CONCLUSIONS: For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts. © 2015 by the American Diabetes Association.

Thomsen T.R.,University of Aalborg | Thomsen T.R.,Danish Technological Institute DTI | Aasholm M.S.,University of Aalborg | Rudkjobing V.B.,University of Aalborg | And 6 more authors.
Wound Repair and Regeneration | Year: 2010

The bacterial microbiota plays an important role in the prolonged healing of chronic venous leg ulcers. The present study compared the bacterial diversity within ulcer material from 14 skin graft operations of chronic venous leg ulcers using culture-based methods and molecular biological methods, such as 16S rRNA gene sequencing, fingerprinting, quantitative polymerase chain reaction, and fluorescence in situ hybridization. Each wound contained an average of 5.4 species but the actual species varied between wounds. The diversity determined by culture-based methods and the molecular biological methods was different. All the wounds contained Staphylococcus aureus, whereas Pseudomonas aeruginosa was in six out of 14 wounds. Molecular methods detected anaerobic pathogens in four ulcers that were not detected with anaerobic culture methods. Quantitative polymerase chain reaction was used to compare the abundance of S. aureus and P. aeruginosa at different locations in the ulcers and their numbers varied greatly between samples taken at different locations in the same ulcer. This should be considered when ulcers are investigated in routine clinical care. The differences between the results obtained with culture-based and molecular-based approaches demonstrate that the use of one approach alone is not able to identify all of the bacteria present in the wounds. © 2010 by the Wound Healing Society.

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