The medial sural artery perforator flap: the first choice for soft-tissue reconstruction about the knee

The gastrocnemius muscle flap may be considered the first choice in many cases of soft-tissue reconstruction about the knee. Limited arc of rotation and reach of the flap as well as unsightly muscle bulk are major disadvantages and were the impetus to look for a local alternative. The aim of this study is to present a consecutive series of patients with a reconstruction about the knee involving the medial sural artery perforator flap (MSAPF)

Comparison of anterolateral thigh and radial forearm free flaps in head and neck reconstruction

The radial forearm flap (RFF) and the anterolateral thigh flap (ALT) are commonly used for the reconstruction of head and neck soft-tissue defects. The aim of the study was to investigate and compare the surgical outcomes, complications and systemic condition of the patient after reconstruction of extensive head and neck defects with ALT or RFF following cancer extirpation

A Simple, Reliable, and Inexpensive Intraoperative External Expansion System for Enhanced Autologous Structural Fat Grafting

External volume expansion of the recipient site by suction has been proposed as a way of improving fat graft survival. The objective of this study was to present an innovative and simple intraoperative external expansion system to enhance small-volume autologous fat grafting (40–80 mL) and to discuss its background and its mechanism of action. In this system, expansion is performed using a complete vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical Innovations). The recipient site is rapidly expanded intraoperatively 10 times for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous fat injection. During this repetitive stimulation, the tissues become grossly expanded, developing macroscopic swelling that regresses slowly over the course of hours following the cessation of the stimulus. The system sets various mechanisms in motion, including scar release, mechanical stimulation, edema, ischemia, and inflammation, which provide an environment conducive for cell proliferation and angiogenesis. In order to maintain the graft construct in its expansive state, all patients are encouraged postoperatively to use the Kiwi three times daily for one minute per session over the course of three days. The handling of this system is simple for both the patients and the surgeon. Satisfactory clinical outcomes have been achieved without significant complications

Aldehyde oxidase activity in human skin explants

Human aldehyde oxidase (AO) is a molybdo-flavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in drug failures, existing in vitro–in vivo correlations are often poor and extrahepatic role of AO is practically unknown. This study investigated enzymatic activity of AO in human skin, the largest organ of the body frequently exposed to therapeutic drugs and xenobiotics. Fresh full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4 hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol•mg skin–1•h–1, resulting in 13% and 2% of substrate turnover after 24 h of incubation with 10 μM of substrate, respectively. Hydroxylation activities for the two substrates were significantly correlated (r2 = 0.769), with interindividual variability ranging from 3 (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4 hydroxylation at 100 μM of the inhibitor. Reaction rates were linear up to 4 h and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation, and p-toluidine N-acetylation, showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin

Phase II Metabolism in Human skin: Skin Explants Show Activities of Glucuronidation, Sulfation, N-Acetylation, Catechol Methylation, and Glutathione Conjugation

Although skin is the largest organ of the human body, drug metabolism in skin tissue is often overlooked and existing experimental models tend to lack sufficient validation. To address these challenges, we studied phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model that contains all skin cell types. Results show that human skin has substantial capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified and quantified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17β estradiol, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 μM substrate incubations spanned almost a 1000-fold: from the highest 4.758 pmol•mg skin–1•h–1 for p toluidine N-acetylation to the lowest 0.006 pmol•mg skin–1•h–1 for 17β estradiol 17 glucuronidation. Interindividual variability was 1.4 to 13.0-fold, depending on the test substrate, being the highest for 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 h, although 24 h incubations enabled detection of metabolites in trace amounts. Phase II reactions were unaffected by the inclusion of cosubstrates, but glucuronidation activity was absent following skin freezing. Activities were higher for lower molecular weight substrates with solvent-accessible surface area below 300 Å2 and polar surface area below 50 Å2. Taken together, the fresh full-thickness skin explants represent an appropriate model to study cutaneous phase II metabolism. Although phase II biotransformation mainly results in drug elimination and detoxification, formation of acyl glucuronides and sulfate conjugates could also play a potential role in skin toxicity processes

Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients’ QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease