Combining angiogenic gene and stem cell therapies for myocardial infarction.

J Gene Med. 2009 Jun 24; Pons J, Huang Y, Takagawa J, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW, Su HBACKGROUND: Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. METHODS: MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. RESULTS: We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. CONCLUSIONS: Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy. Copyright (c) 2009 John Wiley & Sons, Ltd.

The Topical Application of Mitomycin C in the Treatment of Scar Formation and Stenosis in Hollow Organs of the Head and Neck: A Field Report.

Laryngorhinootologie. 2009 Jun 24; Bast F, Risteska K, Jovanovic S, Sedlmaier BTHE TOPICAL APPLICATION OF MITOMYCIN C IN THE TREATMENT OF SCAR FORMATION AND STENOSIS IN HOLLOW ORGANS OF THE HEAD AND NECK: A FIELD REPORTINTRODUCTION: The antibiotic und antitumoral effect of Mitomycin C (MMC), a derivative of STREPTOMYCES CAESPITOSUS, has been known since 1956. Besides its use as an adjunction in the treatment of breast, lung and prostate cancer, or as a second-line cytostatic drug for head and neck squamous cell carcinoma (HNSCC), since 1963, MMC has also been successfully used in the suppression of post-operative scar formation, particularly in the field of ophthalmology. This is due to its modulation of fibroblast activity, which enables decreased scarring and fibrosis. In this résumé, we wish to recapitulate our long years of experience in the topical application of Mitomycin C in the treatment of scar formation and stenosis in head and neck organs. PATIENTS AND METHODS: A retrospective analysis on the basis of clinical disease courses and findings (image documentation, questionnaires, pulmonary function tests) covering an examination period of 10 years, was performed on 40 patients with stenosising lesions and a mean age of 54 years. The fields of application included laryngeal, tracheal, oesophageal stenosis and stenosis of the external ear canal and the choane. RESULTS: After combined application of MMC and surgical intervention in cases of recurrent stenosising processes in head and neck organs, especially the larynx and the trachea, a sustained improvement was achieved in the pre-operative stenosis level as well as in the pre-operative, severely limited, forced inspiratory volume in 1 second (F1V1). CONCLUSION: The topical application of MMC appears to be an effective adjunction as a concept of treatment for stenosising, scar-forming lesions. This topical application, however, is not a substitute for correct diagnosis and appropriate surgical treatment. It must be regarded as a purely adjunctive manoeuvre. During the 10 years in which it was used, the clinical findings confirmed an enhancement in the containment of complex cases without the occurrence of any complications.

Unhealing wound in tissues adjacent to cancer as a result of competitive interactions between the embryonic and mature tissue repair programs.

Med Hypotheses. 2009 Jun 18; Schwartsburd PMTissues adjacent to invasive cancers are characterized by wound non-healing, although wounds in normal tissues heal perfectly with the formation of a scar. Cancer-related disorders responsible for wound non-healing have serious clinical impacts, among which are restrictions for the cancer removal via surgical operation. It is not clear how a cancer is capable of deregulating the program of wound healing in normal differentiated tissues adjacent to the cancer. There is good reason to believe that, in cancers (as in fetal-like tissues), there operates a scar-free healing program similar to embryonic healing, whereas in adult tissues a scar-forming healing program of wound repair acts. It can be expected that competitive interactions between these two opposite programs will disrupt the normal development of the scar-forming healing program in normal tissues adjacent to cancer (NTAC). The aim of the present study was to check this hypothesis by comparing the differences and similarities at different stages of embryonic scar-free wound healing, adult/mature scar-forming wound healing, and cancer-induced non-healing observed in NTAC wounds. The identification of certain principal distinctions in features and key regulators between the programs acting in these types of wound repair can be useful for scar-improving wound repair.

Video-assisted left partial arytenoidectomy by diode laser photoablation for treatment of canine laryngeal paralysis.

Vet Surg. 2009 Jun; 38(4): 439-44Olivieri M, Voghera SG, Fossum TWObjectives- To evaluate the clinical outcome of left partial arytenoidectomy by video-assisted laser diode photoablation as a surgical treatment for canine laryngeal paralysis (LP). Study Design- Case series. Animals- Dogs with bilateral LP (n=20). Methods- After endoscopic diagnosis of bilateral LP, left partial arytenoidectomy was performed by photoablation of arytenoid cartilage tissue using a diode laser (600 mum diameter, 15 W power, 980 nm wave length) to increase the width of the rima glottidis. Outcome was evaluated endoscopically (1 and 6 months) and clinically (1, 6, and 12 months). Results- No substantial complications occurred during photoablation or in the immediate postoperative period. Postoperative width of the rima glottidis ranged from 6 to 10 mm at its widest aspect. At 1 month, respiratory function after walking and short running appeared good. Clinical and endoscopic examination revealed good outcome at 1 and 6 months. At 6 months, there was no evidence of hypertrophic scar, hypertrophic granulation tissue, or stricture of the laryngeal glottis in any dog. Two dogs developed aspiration pneumonia after 12 months. Conclusions- Partial arytenoidectomy using video-assisted diode laser photoablation appears to be an effective technique for treating LP. Clinical Relevance- Partial arytenoidectomy by diode laser photoablation should be considered as an alternative technique for treatment of canine LP.

Novel Pretrichial Browlift Technique and Review of Methods and Complications.

Dermatol Surg. 2009 Jun 22; McGuire CS, Gladstone HBBACKGROUND The upper third of the face is integral to our perception of youth and beauty. While the eyelids anchor this facial cosmetic unit, the eyebrows and forehead are intrinsically linked to the upper eyelids, and their position and texture play an important role in creating pleasing eyes as well as conveying mood and youth. The most common browlifts are performed with endoscopic visualization. Yet, this technique requires special equipment and a prolonged learning curve. OBJECTIVE To demonstrate a novel pretrichial technique and to review different browlift methods and their potential adverse effects. METHODS Case series and review of the literature. RESULTS The pretrichial browlift results in a mild to moderate browlift with secondary smoothing of the forehead topography. Aside from bruising and swelling, it results in minimal adverse effects. Other techniques are also effective but may create a larger scar such as a direct browlift, may be more difficult in terms of approach such as the browpexy, or require endoscopes. CONCLUSION Browlifts are an important procedure in rejuvenating the upper third of the face and improving the overall facial aesthetic appearance. The pretrichial browlift is a less invasive open technique that is safe and effective for the appropriate patient. The authors have indicated no significant interests with commercial supporters.