Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor‐β1‐promoted myofibroblast formation and function

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.     

Acute motor response following a single IVIG treatment course in chronic inflammatory demyelinating polyneuropathy

In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the acute motor response following withdrawal and reestablishment of intravenous immunoglobulin (IVIG) therapy was studied. In a prospectively designed case series 11 CIDP patients in IVIG maintenance therapy were assessed with isokinetic dynamometry, nerve conduction studies, and functional tests. After short‐term withdrawal of IVIG, eight treatment‐responsive patients had a 14.2% (8.6–20.0) loss of isokinetic strength of 12 muscle groups. Three patients remained stable without treatment and were excluded from further study. On days 5 and 10 after reinitiation of IVIG therapy isokinetic muscle strength increased by 5.5% (1.6–9.6) and 11.9% (7.5–16.5), respectively, but there was no further increase at day 15. Improvement of walking velocity and hand function coincided. The minimal F‐wave latency shortened, whereas other electrophysiological parameters remained unchanged. In conclusion, isokinetic dynamometry is a sensitive and clinically relevant method for monitoring the acute response to IVIG treatment in CIDP. Muscle Nerve, 2009     

Early healing after treatment of coronary lesions by thin strut everolimus,or thicker strut biolimus eluting bioabsorbable polymer stents: The SORT-OUT VIII OCT study

Aims

Early healing after drug-eluting stent (DES) implantation may reduce the risk of stent thrombosis. The aim of this study was to compare patterns of early healing after implantation of the thin strut everolimus-eluting Synergy DES (Boston Scientific) or the biolimus-eluting Biomatix Neoflex DES (Biosensors).

Methods and Results

A total of 160 patients with the chronic or acute coronary syndrome were randomized 1:1 to Synergy or Biomatrix DES. Optical coherence tomography (OCT) was performed at baseline and at either 1- or 3-month follow-up. The primary endpoint was a coronary stent healing index (CSHI), a weighted index of strut coverage, neointimal hyperplasia, malapposition, and extrastent lumen. A total of 133 cases had OCT follow-up and 119 qualified for matched OCT analysis. The median CSHI score did neither differ significantly between the groups at 1 month: Synergy 8.0 (interquartile range [IQR]: 3.0; 14.0) versus Biomatrix 8.5 (IQR: 4.0; 15.0) (p = 0.47) nor at 3 months: Synergy 6.5 (IQR: 2.0; 13.0) versus Biomatrix 6.0 (IQR: 4.0; 11.0) (p = 0.83). Strut coverage was 84.6% (IQR: 72.0; 97.9) for Synergy versus 77.6% (IQR: 70.1; 90.3) for Biomatrix (p = 0.15) at 1 month and 90.3% (IQR 79.0; 98.8) (Synergy) versus 83.9% (IQR: 77.5; 92.6) (Biomatrix) (p = 0.068) at 3 months. Pooled 1 - and 3-month coverage was 88.6% (IQR: 74.4; 98.4) for Synergy compared with 80.7% (IQR: 73.2; 90.8) for Biomatrix (p = 0.02).

Conclusions

The early healing response after treatment with the Synergy or Biomatrix DES did not differ significantly as determined by a healing index. The Synergy DES showed overall better early stent strut coverage.