Modification in ICU Design May Affect Delirium and Circadian Melatonin: A Proof of Concept Pilot Study.

OBJECTIVES: Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed. DESIGN: Prospective observational cohort pilot study. SETTING: The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system. PATIENTS: Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time. CONCLUSIONS: Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels.

Clinical wIRA-hyperthermia: heating properties and effectiveness in lower trunk regions and its accordance with ESHO quality criteria for superficial hyperthermia.

PURPOSE: The heating characteristics of water-filtered infrared-A (wIRA) radiation were investigated in vivo in two body regions of healthy humans according to the quality standards of the European Society for Hyperthermic Oncology (ESHO) using an irradiance (infrared-A) of 146 W m-2 as recommended for clinical superficial hyperthermia (HT). METHODS: wIRA was applied to the abdominal wall and lumbar region for 60 min. Skin surface temperature was limited to ≤43 °C. Tissue temperatures were measured invasively at 1-min intervals before, during and after wIRA exposure using five fiber-optical probes at depths of 1-20 mm. RESULTS: Significant differences between body regions occurred during the heating-up phase at depths of 5-15 mm. Thermal steady states were reached at depths ≤5 mm after exposures of 5-6 min, and ≤20 mm after 20 min. On average, the minimum requirements of ESHO were exceeded in both regions by the following factors: ≈3 for the heating rate, ≈2 for the specific absorption rate and ≈1.4 for the temperature rise. Tissue depths with T90 ≥ 40 °C and T50 > 41 °C were ≤10 mm, and ≤20 mm for Tmax ≤ 43 °C. The temperature decay time after termination of irradiation was 1-5 min. Corresponding temperatures were ≤42.2 °C for CEM43 and ≤41.8 °C for CEM43T90, i.e., they are inadequate for direct thermal cell killing. CONCLUSIONS: Thermography-controlled wIRA-HT complies with the ESHO criteria for superficial HT as a radiosensitizer and avoids the risk of thermal skin toxicity.

Hyperhydration of Cancers: A Characteristic Biophysical Trait Strongly Increasing O2, CO2, Glucose and Lactate Diffusivities, and Improving Thermophysical Properties of Solid Malignancies.

Cancers are complex, heterogeneous, dynamic and aggressive diseases exhibiting a series of characteristic biophysical traits which complement the original biological hallmarks of cancers favouring progressive growth, metastasis, and contributing to immune evasion and treatment resistance. One of the prevalent differences between most solid tumors and their corresponding, healthy tissues is a significantly higher water content (hyperhydration) in cancers. As a consequence, cancers have distinctly higher (Fick's) diffusion coefficients D [cm2 s-1] for the respiratory gases O2 and CO2, the key substrate glucose, and for the oncometabolite lactate. In addition, cancers have (a) clearly increased specific heat capacities cp [J g-1 K-1], thus representing high-capacity-tissues upon therapeutic heating induced by electromagnetic irradiation, and (b) higher thermal conductivities k [W m-1 K-1], i.e., increased abilities to conduct heat. Therefore, in diffusion analyses (e.g., when describing critical O2 and glucose supplies or CO2 removal, and the development of hypoxic subvolumes) and for modeling temperature distributions in hyperthermia treatment planning, these specific cancer-related data must be considered in order to reliably reflect oncologic thermo-radiotherapy settings.

Strong correlation between specific heat capacity and water content in human tissues suggests preferred heat deposition in malignant tumors upon electromagnetic irradiation.

PURPOSE: Tumor perfusion is considered to be the principal factor determining the build-up of therapeutically effective thermal fields. This assumes that malignancies have lower perfusions than their homologous tissues. This assumption, however, ignores the fact that several tumor types have higher perfusions than their healthy counterparts. Additionally, flow changes upon hyperthermia (39-43 °C) are non-predictable and extremely heterogeneous. Therefore, modeling temperature distribution further requires a more robust parameter, different in malignancies and healthy tissues, i.e., water content (Cw), which highly determines thermal properties upon electromagnetic irradiation. METHOD: Systematic literature reviews of Cw and specific heat capacities (cp) were conducted up to 28 February 2022, providing an updated, comprehensive data overview based on original manuscripts, reviews and databases. RESULTS: Cw- and cp-values of cancers and their corresponding healthy tissues are presented. Strong correlations between these two parameters are described. In general, malignant tumors have distinctly higher Cw values than their homologous tissues. With increasing Cw in low-water-content normal tissues (<70 wt.%), cp rises exponentially from 1.5 to 3.3 J·g-1·K-1. In high-water-content normal tissues (≥70 wt.%), cp increases linearly from 3.5 to 3.8 J·g-1·K-1. In malignant tumors (>80 wt.%), cp rises linearly from 3.6 to 3.9 J·g-1·K-1. Cancers contain up to 27% more water than their tissues of origin and must be considered as 'high-capacitance-tissues'. CONCLUSIONS: Hyperhydration of cancers result in higher cp-values, causing cancers to be better heat reservoirs than corresponding normal tissues upon electromagnetic irradiation. Reliable, tissue-/cancer-specific cp values must be considered when modeling temperature distributions in hyperthermic treatment.

[Light Therapy for Prevention of Delirium in Critically Ill Patients: What's the Evidence?] / Lichttherapie zur Delirprävention bei Intensivpatienten: Was sagt die Evidenz?

Circadian dysrhythmia affects the majority of ICU patients and has far-reaching effects on organ functioning. At the level of the central nervous system, circadian misalignment facilitates executive cognitive dysfunction and the development of ICU delirium. The pathophysiological mechanisms, especially in the cohort of critically ill patients, appear to be complex, multilayered and far from understood. Results from preliminary research indicate that multidimensional, patient-specific chronotherapeutic concepts developed specifically for the ICU setting may help improve the healing process of patients. Circadian lighting therapy might be a promising intervention in this context.

wIRA-heating of piglet skin and subcutis in vivo: proof of accordance with ESHO criteria for superficial hyperthermia.

PURPOSE: The quality assurance guidelines of the European Society for Hyperthermic Oncology (ESHO) specify the requirements for appropriate superficial heating using phantoms. In this current piglet study, we have examined these requirements under in vivo conditions. MATERIALS AND METHODS: The evaluation is based on simultaneous, invasive temperature measurements at 8 different depths between 2 and 20 mm in the thigh of anesthetized piglets during irradiation with water-filtered infrared radiation (wIRA). Temperature probes were equally distributed in an area of 10 cm diameter of homogeneously irradiated skin. Piglets were irradiated to 126.5 mW cm-2 in the spectral range of IR-A. RESULTS: Heating rates and specific absorption rates were in full accordance with the ESHO standards. Due to early onset of thermoregulation, the desired temperature rise of 6 K at a depth of 5 mm was achieved after about 10 min of exposure, i.e. 4 min later than required for phantoms. After reaching thermal steady state, on average T90 ≥ 40 °C occurred in tissue depths up to 20 mm, T50 ≥ 41 °C up to 16 mm, and a mean CEM43T90 ≈ 1 min was calculated for depths up to 8 mm. CONCLUSIONS: Piglet data are comparable with preliminary literature data assessed in vivo in the abdominal wall and in recurrent breast cancer of humans. The potential of wIRA-HT for adequate treatment of superficial tissues/cancers in the clinical setting thus is confirmed. To ensure therapeutically needed doses of wIRA-HT, irradiation times should be extended.

Thermal field formation during wIRA-hyperthermia: temperature measurements in skin and subcutis of piglets as a basis for thermotherapy of superficial tumors and local skin infections caused by thermosensitive microbial pathogens.

Purpose: The temporal and spatial formation of the temperature field and its changes during/upon water-filtered infrared-A (wIRA)-irradiation in porcine skin and subcutis were investigated in vivo in order to get a detailed physical basis for thermotherapy of superficial tumors and infections caused by thermosensitive microbial pathogens (e.g., Mycobacterium ulcerans causing Buruli ulcer). Methods: Local wIRA-hyperthermia was performed in 11 anesthetized piglets using 85.0 mW cm-2, 103.2 mW cm-2 and 126.5 mW cm-2, respectively. Invasive temperature measurements were carried out simultaneously in 1-min intervals using eight fiber-optical probes at different tissue depths between 2 and 20 mm, and by an IR thermometer at the skin surface. Results: Tissue temperature distribution depended on incident irradiance, exposure time, tissue depths and individual 'physiologies' of the animals. Temperature maxima were found at depths between 4 and 7 mm, exceeding skin surface temperatures by about 1-2 K. Tissue temperatures above 37 °C, necessary to eradicate M. ulcerans at depths <20 mm, were reached reliably. Conclusions: wIRA-hyperthermia may be considered as a novel therapeutic option for treatment of local skin infections caused by thermosensitive pathogens (e.g., in Buruli ulcer). To ensure temperatures required for heat treatment of superficial tumors deeper than 4 mm, the incident irradiance needed can be controlled either by (a) invasive temperature measurements or (b) control of skin surface temperature and considering possible temperature increases up to 1-2 K in underlying tissue.

Biophysical and photobiological basics of water-filtered infrared-A hyperthermia of superficial tumors.

Thermography-controlled, water-filtered infrared-A (wIRA) is a novel, effective and approved heating technique listed in the ESHO quality assurance guidelines for superficial hyperthermia clinical trials (2017). In order to assess the special features and the potential of wIRA-hyperthermia (wIRA-HT), detailed and updated information about its physical and photobiological background is presented. wIRA allows for (a) application of high irradiances without skin pain and acute grade 2-4 skin toxicities, (b) prolonged, therapeutically relevant exposure times using high irradiances (150-200 mW/cm2) and (c) faster and deeper heat extension within tissues. The deeper radiative penetration depth is mainly caused by forward Mie-scattering. At skin surface temperatures of 42-43 °C, the effective heating depth is 15 mm (T ≥ 40 °C) and 20 mm (T ≥ 39.5 °C). Advantages of wIRA include its contact-free energy input, easy power steering by a feed-back loop, extendable treatment fields, real-time and noninvasive surface temperature monitoring with observation of dynamic changes during HT, and - if necessary - rapid protection of temperature-sensitive structures. wIRA makes the compliant heating of ulcerated and/or bleeding tumors possible, allows for HT of irregularly shaped and diffusely spreading tumors, is independent of individual body contours, allows for very short 'transits' between HT and RT (1-4 min) or continuous heating between both therapeutic interventions. New treatment options for wIRA-HT may include malignant melanoma, vulvar carcinoma, skin metastases of different primary tumors, cutaneous T-and B-cell lymphoma, large-area hemangiomatosis, inoperable squamous cell, basal cell and eccrine carcinoma of the skin with depth extensions ≤20 mm.

Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: a retrospective study of 73 patients.

PURPOSE: Evaluation of the efficacy and toxicity of a new setup of thermographically controlled water-filtered infra-red-A (wIRA) superficial hyperthermia (HT) combined with hypofractionated re-irradiation (re-RT) to treat large-sized breast cancer recurrences. METHODS: Records of 73 heavily pre-irradiated patients with 103 treatment regions, treated from September 2009 to July 2015 were retrospectively analysed. Sixty-four patients with macroscopic disease were treated with 94 regions including 46 patients with lymphangiosis carcinomatosa. Hypofractionated RT consisted of 4 Gy once per week up to a total dose of 20 Gy delivered within 1-4 min after wIRA-HT. Heating of tumour nodules and diffusely spreading cancer lesions was performed under real-time thermographic temperature monitoring, maintaining the maximum skin temperature in the ROI between 42 °C and 43 °C, achieving intratumoural temperatures up to a depth of 2 cm between 39.5 °C and 42 °C. Seventeen patients received re-re-irradiation (re-re-RT) using the same HT/RT-treatment schedule. RESULTS: Response rates in patients with macroscopic disease: 61% CR, 33% PR, 5% NC and 1% PD. Local control throughout life time after CR of macroscopic disease: 59%. All nine patients with microscopic disease had CR and local control throughout lifetime. Only grade 1 toxicities were observed. CONCLUSIONS: Application of thermographically controlled wIRA-HT combined with extremely low-dose re-irradiation provides good local control throughout lifetime of heavily pre-treated breast cancer recurrences. The twin wIRA radiator provides a sufficiently homogeneous heat deposition for the treatment of larger areas. The time lag between HT and re-RT is substantially reduced. The possibility of re-re-RT opens new therapeutic options for the future.

From Localized Mild Hyperthermia to Improved Tumor Oxygenation: Physiological Mechanisms Critically Involved in Oncologic Thermo-Radio-Immunotherapy.

(1) Background: Mild hyperthermia (mHT, 39-42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy. mHT triggers a series of therapeutically relevant biological mechanisms, e.g., it can act as a radiosensitizer by improving tumor oxygenation, the latter generally believed to be the commensurate result of increased blood flow, and it can positively modulate protective anticancer immune responses. However, the extent and kinetics of tumor blood flow (TBF) changes and tumor oxygenation are variable during and after the application of mHT. The interpretation of these spatiotemporal heterogeneities is currently not yet fully clarified. (2) Aim and methods: We have undertaken a systematic literature review and herein provide a comprehensive insight into the potential impact of mHT on the clinical benefits of therapeutic modalities such as radio- and immuno-therapy. (3) Results: mHT-induced increases in TBF are multifactorial and differ both spatially and with time. In the short term, changes are preferentially caused by vasodilation of co-opted vessels and of upstream normal tissue vessels as well as by improved hemorheology. Sustained TBF increases are thought to result from a drastic reduction of interstitial pressure, thus restoring adequate perfusion pressures and/or HIF-1α- and VEGF-mediated activation of angiogenesis. The enhanced oxygenation is not only the result of mHT-increased TBF and, thus, oxygen availability but also of heat-induced higher O2 diffusivities, acidosis- and heat-related enhanced O2 unloading from red blood cells. (4) Conclusions: Enhancement of tumor oxygenation achieved by mHT cannot be fully explained by TBF changes alone. Instead, a series of additional, complexly linked physiological mechanisms are crucial for enhancing tumor oxygenation, almost doubling the initial O2 tensions in tumors.

Refinement of water-filtered infrared A (wIRA) irradiations of in vitro acute and persistent chlamydial infections.

Water-filtered infrared A (wIRA) alone or in combination with visible light (VIS) exerts anti-chlamydial effects in vitro and in vivo in acute infection models. However, it has remained unclear whether reduced irradiation duration and irradiance would still maintain anti-chlamydial efficacy. Furthermore, efficacy of this non-chemical treatment option against persistent (chronic) chlamydial infections has not been investigated to date. To address this knowledge gap, we evaluated 1) irradiation durations of 5, 15 or 30 min in genital and ocular Chlamydia trachomatis acute infection models, 2) irradiances of 100, 150 or 200 mW/cm2 in the acute genital infection model and 3) anti-chlamydial activity of wIRA and VIS against C. trachomatis serovar B and E with amoxicillin (AMX)- or interferon γ (IFN-γ)-induced persistence. Reduction of irradiation duration reduced anti-chlamydial efficacy. Irradiances of 150 to 200 mW/cm2, but not 100 mW/cm2, induced anti-chlamydial effects. For persistent infections, wIRA and VIS irradiation showed robust anti-chlamydial activity independent of the infection status (persistent or recovering), persistence inducer (AMX or IFN-γ) or chlamydial strain (serovar B or E). This study clarifies the requirement of 30 min irradiation duration and 150 mW/cm2 irradiance to induce significant anti-chlamydial effects in vitro, supports the use of irradiation in the wIRA and VIS spectrum as a promising non-chemical treatment for chlamydial infections and provides important information for follow-up in vivo studies. Notably, wIRA and VIS exert anti-chlamydial effects on persistent chlamydiae which are known to be refractory to antibiotic treatment.

Spectral Remittance and Transmittance of Visible and Infrared-A Radiation in Human Skin-Comparison Between in vivo Measurements and Model Calculations.

The aim of the study was to assess the interindividual variability of spectral remittance and spectral transmittance of visible and infrared-A radiations interacting with human skin and subcutaneous tissue, and direct measurements were taken in vivo using healthy persons of different skin color types. Up to wavelengths of about 900 nm, both spectral remittance and spectral transmittance depended significantly on the individual contents of melanin and hemoglobin in the skin, whereas the contents of water and lipids mainly determined spectral slopes of both characteristics of interaction for wavelengths above about 900 nm. In vivo measured data of spectral transmittance showed approximately similar decreases with tissue thickness between about 900 nm and 1100 nm as compared with model data which were calculated using spectral absorption and scattering coefficients of skin samples in vitro published by different authors. In addition, in vivo measured data and in vitro-based model calculations of spectral remittance were approximately comparable in this wavelength range. In contrast, systematic but individually varying differences between both methods were found for both spectral remittance and spectral transmittance at wavelengths below about 900 nm, where interaction of radiation was significantly affected by both melanin and hemoglobin.

Sustained Increase of 25-Hydroxyvitamin D Levels in Healthy Young Women during Wintertime after Three Suberythemal UV Irradiations-The MUVY Pilot Study.

OBJECTIVES: Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study "MUVY" (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design. METHODS: 20 healthy young women (Fitzpatrick skin types I-III, aged 21-25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50. RESULTS: Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0-8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4-18.4) and 26.2 pmol/L (95%CI = 7.2-45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale "Vigor/Activity" and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8. CONCLUSIONS: Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274.

Effects of Narrow-band IR-A and of Water-Filtered Infrared A on Fibroblasts.

Exposures of the skin with electromagnetic radiation of wavelengths between 670 nm and 1400 nm are often used as a general treatment to improve wound healing and reduce pain, for example, in chronic diabetic skin lesions. We investigated the effects of water-filtered infrared A (wIRA) and of narrow-band IR-A provided by a light-emitting diode LED (LED-IR-A) irradiation in vitro on 3T3 fibroblast cultures under defined conditions with and without glyoxal administration. Glyoxal triggers the formation of advanced glycation end products, thereby mimicking a diabetic metabolic state. Cell viability and apoptotic changes were determined by flow cytometry after vital staining with Annexin V, YO-PRO-1 and propidium iodide (PI), and by SubG1 assay. Mitochondrial function and oxidative stress were examined by vital staining for radical production, mitochondrial membrane potential (MMP) and the ratio of reduced-to-oxidized glutathione (GSH/GSSG). The metabolic state was monitored by a resazurin conversion assay. The numbers of apoptotic cells were reduced in cultures irradiated with wIRA or LED-IR-A. More mitochondria showed a well-polarized MMP after wIRA irradiation in glyoxal damaged cells. LED-IR-A treatment specifically restored the GSH/GSSG ratio. The immediate positive effects of wIRA and LED-IR-A observed in living cells, particularly on mitochondria, reflect the therapeutic benefits of wIRA and LED-IR-A.

Bivalent effect of UV light on human skin mast cells-low-level mediator release at baseline but potent suppression upon mast cell triggering.

Ultraviolet (UV) irradiation is an established treatment for inflammatory skin diseases, although the precise mode of action is still unclear. Activating and suppressive effects on mast cell (MC) mediator release have been described. The aim of this study was to investigate systematically the effects of UVB, UVA-1, and psoralen plus UVA-1 at therapeutic doses on skin-derived human MC. Baseline and stimulated release of histamine, tryptase, and of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were examined. In resting MC, UV light induced a slight, yet significant histamine release corresponding to enhanced surface levels of lysosome-associated membrane proteins (LAMP). In contrast, UV pre-treatment caused a marked suppression of the anti-IgE-induced histamine release, accompanied by a diminished, anti-IgE-mediated increase in LAMP expression. The secretion of IL-6, IL-8, and TNF-alpha was inhibited in resting and activated MC, suggesting a different mode of action. Regarding the importance of MC in a variety of allergic and inflammatory processes, our data show a high susceptibility of this cell type towards UV light, which seems to partially depend on the state of cellular activation. Immunosuppressive effects predominate in activated MC, thus corresponding with the beneficial effects in inflammatory diseases, whereas in resting MC, both stimulatory and inhibitory effects are observed.

Ultraviolet B radiation-mediated inhibition of interferon-gamma-induced keratinocyte activation is independent of interleukin-10 and other soluble mediators but associated with enhanced intracellular suppressors of cytokine-signaling expression.

Ultraviolet irradiation represents a well-established treatment modality for inflammatory skin diseases. The aim of this study was to investigate the mechanisms of ultraviolet B radiation-induced keratinocyte insensitivity towards interferon-gamma. Flow cytometric analyses indicated that ultraviolet B radiation temporarily inhibits the interferon-gamma-induced activation of primary keratinocyte and HaCaT cells as measured by reduced intercellular adhesion molecule-1 (CD54) and HLA-DR upregulation. Western blot experiments have suggested that this is mediated by the ultraviolet B radiation-induced inhibition of signal transduction and transcription factor-1 phosphorylation. Neither interleukin-10 neutralization nor interleukin-10 addition had any effect on the ultraviolet B radiation-induced inhibition of interferon-gamma induced intercellular adhesion molecule-1 expression. Furthermore, the supernatant from ultraviolet B-irradiated cells failed to inhibit the interferon-gamma-induced CD54 and HLA-DR upregulation in nonradiated HaCaT cells. Moreover, irradiated cells from whom the supernatant was withdrawn 4 h after irradiation still showed a diminished interferon-gamma-induced response after 24 h. Thus, not soluble but intracellular factors might be involved in the ultraviolet B radiation-induced inhibition of interferon-gamma-induced keratinocyte activation. Therefore, we analyzed the expression of members of suppressors of cytokine-signaling (SOCS) molecules using real-time polymerase chain reaction. We found a fast and strong upregulation of SOCS1 and SOCS3 but not of SOCS2 after ultraviolet B radiation. Similarly, ultraviolet B radiation induced the expression of these particular SOCS molecules in lesional psoriatic skin. As SOCS molecules are known inhibitors of signal transduction and transcription factor phosphorylation, which is essential for interferon-gamma-induced intercellular adhesion molecule-1 and HLA-DR upregulation, this may explain the interferon-gamma unresponsiveness after ultraviolet B radiation.

Protection against UVB irradiation by natural filters extracted from lichens.

Natural substances extracted from lichens and boldo tree were tested in vivo and in vitro as possible UV-light filters. The protection factors were compared with that found for the references: Nivea sun Spray LSF 5, octylmethoxycinnamate (OMC) and 4-tert.-butyl-4'-methoxy dibenzoylmethane (BM-DBM). The stability of the single compounds was studied through UV-Vis spectroscopy. Usnic acid resulted to be the best UVB filter, with an in vivo protection factor similar to Nivea sun Spray LSF 5. Most of the single compounds studied in vitro resulted to have higher or similar filtering power than octylmethoxycinnamate. The protection factors as well as the good UV-light absorption of their photo-products suggest that these natural substances may be useful as new filters in sun-screen preparations.

Effects of water-filtered infrared-A and of heat on cell death, inflammation, antioxidative potential and of free radical formation in viable skin--first results.

The effects of water-filtered infrared-A (wIRA) and of convective heat on viability, inflammation, inducible free radicals and antioxidative power were investigated in natural and viable skin using the ex vivo Bovine Udder System (BUS) model. Therefore, skin samples from differently treated parts of the udder of a healthy cow were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, by prostaglandin E2 (PGE2) measurement and by electron spin resonance (ESR) spectroscopy. Neither cell viability, the inflammation status, the radical status or the antioxidative defence systems of the skin were significantly affected by wIRA applied within 30 min by using an irradiance of 1900 W m(-2) which is of relevance for clinical use, but which exceeded the maximum solar IR-A irradiance at the Earth's surface more than 5 times and which resulted in a skin surface temperature of about 45 °C without cooling and of about 37 °C with convective cooling by air ventilation. No significant effects on viability and on inflammation were detected when convective heat was applied alone under equivalent conditions in terms of the resulting skin surface temperatures and exposure time. As compared with untreated skin, free radical formation was almost doubled, whereas the antioxidative power was reduced to about 50% after convective heating to about 45 °C.

The interpretation of clinical studies on the photodynamic treatment of actinic keratosis.

Actinic keratosis is one of the most commonly treated skin conditions. A number of studies have recently been published on the treatment of this ailment using photodynamic therapy. The authors of this letter are concerned about the interpretation of some of these studies and would like to outline possible misinterpretations which may arise due to an incomplete analysis of the study reports available. Clearly, the "ideal" therapy for actinic keratosis should be a carefully chosen compromise between undesired side-effects and therapeutic efficacy and needs to be based on a consideration of all of the relevant clinical studies.