Sigrid Karrer

A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients

Background  Bacterial colonization of chronic wounds slows healing. Cold atmospheric plasma has been shown in vitro to kill a wide range of pathogenic bacteria.

Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial

Background  The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems.

Oxygen in acute and chronic wound healing

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.

Plasma applications in medicine with a special focus on dermatology

The recent tremendous progress in understanding physical plasma phenomenon, together with the development of new plasma sources has put growing focus on the application of plasmas in health care. Active plasma components, such as molecules, atoms, ions, electrons and photons, reactive species, ultraviolet radiation, optical and infrared emission and heat have the ability of activating, controlling and catalysing reactions and complex biochemical procedures. Thermal and non‐thermal (i.e. cold) plasmas – both already widely established in medicine – are used for various therapeutic applications. Particularly in dermatology, plasma applications hold big potential, for example, in wound healing, such as efficient disinfection or sterilization, therapy of various skin infections or tissue regeneration. This review gives an overview on potential plasma applications in medicine – including the recent research on skin diseases – and summarizes possible interactions between plasmas and living tissue.

Plasma medicine: possible applications in dermatology

As a result of both the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative field of research showing high potential. While thermal plasmas have long been used in various medical fields (for instance for cauterization and sterilization of medical instruments), current research mainly focuses on application of non‐thermal plasmas.

INDOCYANINE GREEN: INTRACELLULAR UPTAKE AND PHOTOTHERAPEUTIC EFFECTS IN VITRO

Indocyanine green (ICG; absorption peak in human plasma 805 nm) was investigated for ICG-mediated phototherapy in vitro. The cellular uptake of ICG (1 microM-50 microM) into HaCaT keratinocytes after an incubation period of 24 h increased up to an intracellular ICG concentration of 12.1 +/- 1.3 nmol per 10(6) cells. To examine dose dependent phototoxic effects in vitro, keratinocytes were incubated with 0 microM-50 microM ICG for 24 h and irradiated by a diode laser (805 nm) with different energy densities (0, 12, 24, 48 J cm-2). All applied ICG concentrations except for 5 microM yielded a cell killing effect in combination with irradiation depending significantly on ICG concentration and light dose. Cell viability for dark control and cells incubated with 50 microM ICG and irradiated with 48 J cm-2 was 0.82 +/- 0.15 and 0.07 +/- 0.02, respectively. Sodium azide (100 mM), a quencher of reactive oxygen species, inhibited significantly the cell killing using 50 microM ICG and 24 J cm-2. Taken together, photoactivation of ICG by irradiation with a diode laser was shown to induce effectively cell killing of HaCaT keratinocytes. Moreover, this effect was inhibited by sodium azide, thus irradiation of ICG might induce a photodynamic reaction.

Photodynamic Therapy with Topical Application of 5-Aminolevulinic Acid in the Treatment of Actinic Keratoses: An Initial Clinical Study

BACKGROUND The incidence of actinic keratoses (AK) is rising and there is still a need for therapeutic alternatives. OBJECTIVE To demonstrate the efficacy and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) in the treatment of AK. METHODS Ten patients with 36 lesions (19 at hands and arms, 17 on the head) received ALA-PDT once (occlusive application of a 10% ALA emulsion for 6 h, irradiation with red light, 580-740 nm, 150 J/cm2) and were then monitored for 3 months. Therapeutic efficacy was judged using a score evaluating infiltration and keratosis of AK. RESULTS After 28 days, significantly lower score sums were observed (head: mean = 15%; hand: mean = 67%) compared to the initial score (100%). Complete remission was achieved in 71% of AK localized on the head. No notable side effects were observed. CONCLUSION This study demonstrated the potential of good efficacy and tolerability in the treatment of AK using topical ALA-PDT. How efficacy for lesions on the hand can be improved and whether PDT is able to concur with established treatment modalities remains to be shown in further studies.

Photodynamic therapy in dermatology: an update

Topical photodynamic therapy (PDT) is a well‐established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowens disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5‐aminolevulinic acid (5‐ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light‐emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2–3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment.

Cold atmospheric plasma (CAP) changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo.

Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.

Topical photodynamic therapy for localized scleroderma.

Therapy of localized scleroderma is unsatisfactory, with numerous treatments being used that have only limited success or considerable side-effects. The aim of this trial was to determine whether topical photodynamic therapy would be effective in patients with localized scleroderma. Five patients with progressive disease, in whom conventional therapies had failed, were treated by application of a gel containing 3% 5-aminolevulinic acid followed by irradiation with an incoherent lamp (40 mW/cm2, 10 J/cm2). The treatment was performed once or twice weekly for 3-6 months. In all patients the therapy was highly effective for sclerotic plaques, as measured by a quantitative durometer score and a clinical skin score. The only side-effect was a transient hyperpigmentation of the treated lesions. These cases document the beneficial effect of topical photodynamic therapy in localized scleroderma. Controlled trials are now necessary to confirm these preliminary results.