Proteomics Studies Suggest That Nitric Oxide Donor Furoxans Inhibit In Vitro Vascular Smooth Muscle Cell Proliferation by Nitric Oxide-Independent Mechanisms.

Physiologically, smooth muscle cells (SMC) and nitric oxide (NO) produced by endothelial cells strictly cooperate to maintain vasal homeostasis. In atherosclerosis, where this equilibrium is altered, molecules providing exogenous NO and able to inhibit SMC proliferation may represent valuable antiatherosclerotic agents. Searching for dual antiproliferative and NO-donor molecules, we found that furoxans significantly decreased SMC proliferation in vitro, albeit with different potencies. We therefore assessed whether this property is dependent on their thiol-induced ring opening. Indeed, while furazans (analogues unable to release NO) are not effective, furoxans' inhibitory potency parallels with the electron-attractor capacity of the group in 3 of the ring, making this effect tunable. To demonstrate whether their specific block on G1-S phase could be NO-dependent, we supplemented SMCs with furoxans and inhibitors of GMP- and/or of the polyamine pathway, which regulate NO-induced SMC proliferation, but they failed in preventing the antiproliferative effect. To find the real mechanism of this property, our proteomics studies revealed that eleven cellular proteins (with SUMO1 being central) and networks involved in cell homeostasis/proliferation are modulated by furoxans, probably by interaction with adducts generated after degradation. Altogether, thanks to their dual effect and pharmacological flexibility, furoxans may be evaluated in the future as antiatherosclerotic molecules.

High-density hyaluronic acid for the treatment of HIV-related facial lipoatrophy.

BACKGROUND: Facial lipoatrophy is a stigmatizing hallmark of HIV. The injection of facial fillers has an essential role in the treatment of this condition. The objective of our study was to verify the safety and efficacy of a new formulation of high-density hyaluronic acid for the injectable treatment of HIV-related facial lipoatrophy. METHODS: We treated with high-density hyaluronic acid injections HIV patients affected by moderate to severe facial lipoatrophy and evaluated them at last follow-up, at a minimum of 36 weeks. Physician-related outcomes included pre-and post-treatment ultrasound measurement of the soft-tissue thickness of the cheeks and qualitative assessment of aesthetic results by means of the Global Aesthetic Improvement Scale using pre- and post-treatment photos of the patients. Patient satisfaction outcomes were evaluated with the VAS-face scale and Freiburg test. RESULTS: Fifty-four patients were studied. The median number of treatment sessions was 3 and the median length of treatment was 5.5 months. The thickness of the soft tissues of the cheek increased significantly from 9.45 to 13.12 mm (p<0.0001). On the basis of the Global Aesthetic Improvement Scale, 87.5% of the patients were judged as "much improved" or "improved." Patient satisfaction at 1 year from the end of treatment was proven (VAS-face: 77.9; Freiburg questionnaire: 93.6% of patients were satisfied or very satisfied). Complications were limited to mild redness and swelling in the early postoperative period. CONCLUSION: Long-term improvement of facial contour and excellent patient satisfaction, in the absence of severe side effects, were obtained by the injection of high-density hyaluronic acid (STYLAGE® XL) in HIV patients with facial lipoatrophy.

Improvement of the Rotation Arch of the Posterior Interosseous Pedicle Flap Preserving Both Reverse Posterior and Anterior Interosseous Vascular Sources.

PURPOSE: The reverse posterior interosseous artery flap has several advantages, not sacrificing any major blood vessel, but its relatively short pedicle limits the use to cover defects up to the metacarpophalangeal joint. Our purpose is to demonstrate that the ligature of the anterior interosseous artery (AIA), proximal to the communicating branch with the posterior interosseous artery, leads to an improved flap rotation arch, preserving both vascular sources. METHODS: Sixteen fresh cadavers with latex perfusion were analyzed before and after our technique of elongation, and the so-obtained measures were standardized in "percentage of elongation of the pedicle." Eight patient with the loss of substance at the dorsal aspect of the hand have been treated with this technique, and results were evaluated in terms of flap survival and complication rates. RESULTS: The medium length of the pedicle in the normal flap was 10.8 cm, and after the section of the AIA, the medium length of the pedicle was 13.6 cm with a medium increase of 2.8 cm. It means a medium increase of 24% of the length of the pedicle. In all patients treated, full coverage of the defect was obtained, and we did not experience major complications. CONCLUSIONS: This anatomical study supported by our clinical experience demonstrates that the use of the variant described above permits to reach more distal part of the hand without being afraid to stretch the pedicle because of the connection with the anastomotic arcades of the AIA at the wrist reducing the risk of ischemia of the flap.