Single Dose of Sildenafil and Atorvastatin Increase Skin Survivability, but only Atorvastatin Increase Nitric Oxide in Rat Ischeamia Reperfusion Model.

Background: Ischeamia reperfusion injury is a frequent challenge during tissue reconstruction. Atorvastatin and Sildenafil, have been studied for their protective and/or therapeutic effects on various organ systems subjected to IRI. The aim of the present study was to compare a single dose of Atorvastatin and Sildenafil pretreatment on acute oxidative/nitrosative stress and the subsequent dermal flap necrosis. Materials and Methods: Forty-five Sprague-Dawley rats, were randomly allocated into three equal groups(n=15): Group A: Control rats treated with intraperitoneal saline, Group B: Sildenafil group, and Group C: atorvastatin group. All rats underwent flap elevation and inferior epigastric artery occlusion thirty minutes after drug administration. Myeloperoxidase activity, malondialdehyde levels and inducible nitric oxide synthase activity were evaluated 12 hours after reperfusion. Flap survivability was analysed 7 days after the procedure. Results: Statistically significant reduction was detected in sildenafil and atorvastation. Measurements of myelopyroxidase followed a similar pattern, interestingly malonadehyde levels measured to be significantly lower in the sildenafil group. Contrary, iNOS activity atorvastatin was significantly elevated in atorvastatin group. Conclusion: The single dose of atorvastatin or sildenafil increase flap survivability almost equally, however only atorvastatin enhances significantly iNOS expression.

Defining Normal Parameters for the Male Nipple-Areola Complex: A Prospective Observational Study and Recommendations for Placement on the Chest Wall.

BACKGROUND: The nipple-areola complex (NAC) is important aesthetically and functionally for both sexes. Methods for positioning the NAC in males are less well established in the literature compared to females but are just as important. OBJECTIVES: This study aims to determine the normal parameters for the male NAC, to review literature, and to present a reliable method for preoperative placement. METHODS: Normal male patients, with no prior chest wall conditions, were prospectively recruited to participate. General demographics and chest wall dimensions were recorded-sternal notch to nipple (SNND), internipple (IND), anterior axillary folds distances (AFD), NAC, and chest circumference were measured. Comparisons were made using t test and ANOVA. RESULTS: One hundred and fifty-eight patients were recruited (age range, 18-90 years); mostly (86.7%) with normal or overweight BMI. The IND averaged 249.4 mm, the SNND averaged 204.2 mm, and the AFD averaged 383.8 mm. Areola diameter averaged 26.6 mm and for the nipple, 6.9 mm. The IND:AFD ratio was 0.65. There was no statistical difference in the IND:AFD ratio, SNND, or NAC parameters comparing different ethnic groups. The SNND increased with greater BMI (P ≤ 0.001). Using these data, we suggest ideal NAC dimensions and devised a simple method for positioning of the NAC on the male chest wall. CONCLUSIONS: This is the largest study, with the widest range in age and BMI, to date on this topic. Although fewer men than women undergo surgery to the breast, there is a growing awareness for enhancing the appearance of the male chest wall.

Innovations in Stem Cell Therapy for Diabetic Wound Healing.

Significance: The global burden of diabetic wounds, particularly diabetic foot ulcers, continues to have large economic and social impact throughout the world. Current strategies are not sufficient to overcome this burden of disease. Finding newer, more advanced regenerative cell and tissue-based strategies to reduce morbidity remains paramount. Recent Advances: Recent advances in stem cell therapies are discussed. We also highlight the practical issues of translating these advancing technologies into the clinical setting. Critical Issues: We discuss the use of somatic and induced pluripotent stem cells and the stromal vascular fraction, as well as innovations, including the use of 3D bioprinting of skin. We also explore related issues of using regenerative techniques in clinical practice, including the current regulatory landscape and translatability of in vivo research. Future Directions: Advances in stem cell manipulation showcase the best therapeutic resources available to enhance mechanisms of wound healing such as angiogenesis, cell proliferation, and collagen synthesis; potential methods include changing the scaffold microenvironment, including relative oxygen tension, and the use of gene modification and nanotechnology. Secretome engineering, particularly the use of extracellular vesicles, may be another potential cell-derived therapeutic that may enable use of cell-free translational therapy.

Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo.

CD1d-restricted NKT cells rapidly stimulate innate and adaptive immunity through production of Th1 and/or Th2 cytokines and induction of CD1d(+) APC maturation. However, therapeutic exploitation of NKT cells has been hampered by their paucity and defects in human disease. NKT cell-APC interactions can be modeled by direct stimulation of human APCs through CD1d in vitro. We have now found that direct ligation with multiple CD1d mAbs also stimulated bioactive IL-12 release from CD1d(+) but not CD1d knockout murine splenocytes in vitro. Moreover, all of the CD1d mAbs tested also induced IL-12 as well as both IFN-gamma and IFN-alpha in vivo from CD1d(+) but not CD1d-deficient recipients. Unlike IFN-gamma, CD1d-induced IFN-alpha was at least partially dependent on invariant NKT cells. Optimal resistance to infection with picornavirus encephalomyocarditis virus is known to require CD1d-dependent APC IL-12-induced IFN-gamma as well as IFN-alpha. CD1d ligation in vivo enhanced systemic IL-12, IFN-gamma, and IFN-alpha and was protective against infection by encephalomyocarditis virus, suggesting an alternative interpretation for previous results involving CD1d "blocking" in other systems. Such protective responses, including elevations in Th1 cytokines, were also seen with CD1d F(ab')(2)s in vivo, whereas an IgM mAb (with presumably minimal tissue penetration) was comparably effective at protection in vivo as well as cytokine induction both in vivo and in vitro. Although presumably acting immediately "downstream," CD1d mAbs were protective later during infection than the invariant NKT cell agonist alpha-galactosylceramide. These data indicate that NKT cells can be bypassed with CD1d-mediated induction of robust Th1 immunity, which may have therapeutic potential both directly and as an adjuvant.

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach.

A case of spontaneous bilateral Achilles tendon rupture: surgical treatment with early mobilization.

BACKGROUND: Tendo-Achilles (TA) rupture is the most commonly ruptured tendon in the lower limb despite being one of the toughest tendons. Typically, it occurs unilaterally in middle-aged individuals who participate in strenuous activity. Spontaneous ruptures without any risk factors predisposing the patient is uncommon and for it to occur bilaterally is very rare. OBJECTIVES: To raise awareness of the potential for TA ruptures to occur bilaterally and thus the importance of assessing the TA contralateral to a seemingly unilateral rupture. This is particularly the case in patients with risk factors, which are reviewed in this report. A summary of the main treatment options is also described. CASE REPORT: We report a case of spontaneous, bilateral TA rupture in a 40-year-old man with no identifiable risk factors. It occurred following a heavy impact during a sports activity and although painful, was able to mobilize slowly. After a clinical examination confirmed the diagnosis, the patient underwent early bilateral surgical repair and subsequently embarked on a comprehensive rehabilitation program with a good functional outcome at follow-up. His return to premorbid work and social life was uneventful. CONCLUSIONS: Bilateral TA ruptures are rare but increased awareness would help avoid a tear or rupture of the contralateral side being missed. All patients presenting clinically with any TA rupture should have risk factors reviewed. Surgical repair must be accompanied by a comprehensive rehabilitation program for adequate recovery and return of function.