Collagen V-induced nasal tolerance downregulates pulmonary collagen mRNA gene and TGF-beta expression in experimental systemic sclerosis.

BACKGROUND: The purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and TGF-beta expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance. METHODS: Female New Zealand rabbits (N = 12) were immunized with 1 mg/ml of collagen V in Freund's adjuvant (IM). After 150 days, six immunized animals were tolerated by nasal administration of collagen V (25 microg/day) (IM-TOL) daily for 60 days. The collagen content was determined by morphometry, and mRNA expressions of types I, III and V collagen were determined by Real-time PCR. The TGF-beta expression was evaluated by immunostaining and quantified by point counting methods. To statistic analysis ANOVA with Bonferroni test were employed for multiple comparison when appropriate and the level of significance was determined to be p < 0.05. RESULTS: IM-TOL, when compared to IM, showed significant reduction in total collagen content around the vessels (0.371 +/- 0.118 vs. 0.874 +/- 0.282, p < 0.001), bronchioles (0.294 +/- 0.139 vs. 0.646 +/- 0.172, p < 0.001) and in the septal interstitium (0.027 +/- 0.014 vs. 0.067 +/- 0.039, p = 0.026). The lung tissue of IM-TOL, when compared to IM, showed decreased immunostaining of types I, III and V collagen, reduced mRNA expression of types I (0.10 +/- 0.07 vs. 1.0 +/- 0.528, p = 0.002) and V (1.12 +/- 0.42 vs. 4.74 +/- 2.25, p = 0.009) collagen, in addition to decreased TGF-beta expression (p < 0.0001). CONCLUSIONS: Collagen V-induced nasal tolerance in the experimental model of SSc regulated the pulmonary remodeling process, inhibiting collagen deposition and collagen I and V mRNA synthesis. Additionally, it decreased TGF-beta expression, suggesting a promising therapeutic option for scleroderma treatment.

A New Pedicled Internal Mammary Osteomyocutaneous Chimeric Flap (PIMOC) for Salvage Head and Neck Reconstruction: Anatomic Study and Clinical Application.

Well-vascularized composite tissue offers improved outcomes for complex head and neck reconstruction. Patients with vessel-depleted necks and failed reconstructions require alternative reconstructive options. We describe a pedicled internal mammary artery osteomyocutaneous chimeric flap (PIMOC) for salvage head and neck reconstruction. Bilateral dissections of 35 fresh cadavers were performed to study individual tissue components and vascular pedicles to develop the PIMOC technique. The flap was then utilized in a series of patients with vessel-depleted neck anatomy. The PIMOC was dissected bilaterally in all cadavers and there were no statistical differences in vascular pedicle caliber or length with regards to laterality or gender. Five patients subsequently underwent this procedure. The flaps included a vertical rectus abdominis myocutaneous component and a 6th or 7th rib with adjacent muscle and skin to restore bone defects, internal lining, and external coverage. All donor sites were closed primarily. There were no flap losses and all patients gained improvements in facial contour, speech and swallow. Although technically complex, the PIMOC is reproducible and provides a safe and reliable option for salvage head and neck reconstruction. The harvest of the 6th or 7th rib and rectus abdominis muscle renders an acceptable donor site.