Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldha) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2γc mice, lacking lymphocytes and NK cells, and in Ifng mice, Ldha and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and NK cells, resulting in diminished IFN-γ production. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients. Our results demonstrate that lactic acid is a potent inhibitor of function and survival of T and NK cells leading to tumor immune escape.

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.

In wound healing, a variety of mediators have been identified throughout the years. The mediators discussed here comprise growth factors, cytokines and chemokines. These mediators act via multiple (specific) receptors to facilitate wound closure. As research in the last years has led to many new findings, there is a need to give an overview on what is known, and on what might possibly play a role as a molecular target for future wound therapy. This review aims to keep the reader up to date with selected important and novel findings regarding growth factors, cytokines and chemokines in wound healing.

Background: Intense pulsed light (IPL) devices use flashlamps and bandpass filters to emit polychromatic incoherent high-intensity pulsed light of determined wavelength spectrum, fluence, and pulse duration. Similar to lasers, the basic principle of IPL devices is a more or less selective thermal damage of the target. The combination of prescribed wavelengths, fluences, pulse durations, and pulse intervals facilitates the treatment of a wide spectrum of skin conditions. Objective: To summarize the physics of IPL, to provide guidance for the practical use of IPL devices, and to discuss the current literature on IPL in the treatment of unwanted hair growth, vascular lesions, pigmented lesions, acne vulgaris, and photodamaged skin and as a light source for PDT and skin rejuvenation. Methods: A systematic search of several electronic databases, including Medline and PubMed and the authors experience on intense pulsed light. Results: Numerous trials show the effectiveness and compatibility of IPL devices. Conclusion: Most comparative trials attest IPLs similar effectiveness to lasers (level of evidence: 2b to 4, depending on the indication). However, large controlled and blinded comparative trials with an extended follow-up period are necessary. Lasers Surg. Med. 42:93-104, 2010.

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Luminescence imaging of biological parameters is an emerging field in biomedical sciences. Tools to study 2D pH distribution are needed to gain new insights into complex disease processes, such as wound healing and tumor metabolism. In recent years, luminescence-based methods for pH measurement have been developed. However, for in vivo applications, especially for studies on humans, biocompatibility and reliability under varying conditions have to be ensured. Here, we present a referenced luminescent sensor for 2D high-resolution imaging of pH in vivo. The ratiometric sensing scheme is based on time-domain luminescence imaging of FITC and ruthenium(II)tris-(4,7-diphenyl-1,10-phenanthroline). To create a biocompatible 2D sensor, these dyes were bound to or incorporated into microparticles (aminocellulose and polyacrylonitrile), and particles were immobilized in polyurethane hydrogel on transparent foils. We show sensor precision and validity by conducting in vitro and in vivo experiments, and we show the versatility in imaging pH during physiological and chronic cutaneous wound healing in humans. Implementation of this technique may open vistas in wound healing, tumor biology, and other biomedical fields.hydrogen | sensors and probes | fluorescence | skin | dermatology T here is great interest in luminescence imaging of essential biological parameters, such as pH, pO 2 , hydrogen peroxide (H 2 O 2 ), and Ca 2+ , at the moment (1-6). Recently, luminescence-based methods for pH measurement have been developed (7,8). However, a method for in vivo studies on human subjects has not yet been realized. The major challenges for in vivo applications are that biocompatibility and reliability under varying conditions (illumination, oxygen, and temperature) have to be ensured. The standard tool for pH measurement, the glass electrode (9), is not approved for clinical use and only allows single-spot measurements, which makes 2D imaging impossible.Multiple methods for pH imaging exist: ratiometric luminescent pH detection is a straightforward and referenced approach, which has been used, for instance, to measure intracellular pH. In these works, either combinations of dextran-conjugated indicator and reference dyes (fluorescein/tetramethylrhodamine and pHrodo/ rhodamine-green) or seminaphtho-rhodafluor (SNARF) derivatives have been used (10-12). However, to obtain 2D images, either modifications of the optical system during measurements or the use of an image splitter are necessary to separate the signals. Ratiometric methods may suffer from Förster's fluorescence resonance energy transfer (FRET) and most importantly, from differential photobleaching of indicator/reference dyes. The latter problem may be avoided by using intrinsically referenced luminescence lifetime imaging (LLI) of one single pH indicator. LLI has been used for high-resolution 2D and 3D pH mapping in studies on cells, tissue samples, and artificial skin constructs (13-15). These techniques are, however, difficult to implement in studies on live human subject...

Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications.

The process of cutaneous wound healing comprises three overlapping major phases: inflammation, proliferation and tissue remodelling. However, while mechanisms are studied scientifically on the cellular and subcellular level, there is still a lack of knowledge concerning basic clinical parameters like wound pH or pO2. It could be proven that wound healing is affected by wound pH changes as they can lead to an inhibition of endogenous and therapeutically applied enzymes. Besides, the conformational structure of proteins and their functionality in wound healing is altered. Furthermore, the likelihood of bacterial colonization, which is a common problem in chronic wound pathogenesis, is affected by wound pH alterations. However, wound pH is rarely taken into account in current wound therapy strategies. A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy.