Although anti-cancer properties of the natural compound curcumin have been reported, low absorption and rapid metabolisation limit clinical use. The present study investigated whether irradiation with visible light may enhance the inhibitory effects of low-dosed curcumin on prostate cancer cell growth, proliferation, and metastasis in vitro. DU145 and PC3 cells were incubated with low-dosed curcumin (0.1-0.4 mu g/mL) and subsequently irradiated with 1.65 J/cm(2) visible light for 5 min. Controls remained untreated and/or non-irradiated. Cell growth, proliferation, apoptosis, adhesion, and chemotaxis were evaluated, as was cell cycle regulating protein expression (CDK, Cyclins), and integrins of the alpha- and beta-family. Curcumin or light alone did not cause any significant effects on tumor growth, proliferation, or metastasis. However, curcumin combined with light irradiation significantly suppressed tumor growth, adhesion, and migration. Phosphorylation of CDK1 decreased and expression of the counter-receptors cyclin A and B was diminished. Integrin alpha and beta subtypes were also reduced, compared to controls. Irradiation distinctly enhances the anti-tumor potential of curcumin in vitro and may hold promise in treating prostate cancer.

Recent documentation shows that a curcumin-induced growth arrest of renal cell carcinoma (RCC) cells can be amplified by visible light. This study was designed to investigate whether this strategy may also contribute to blocking metastatic progression of RCC. Low dosed curcumin (0.2 µg/mL; 0.54 µM) was applied to A498, Caki1, or KTCTL-26 cells for 1 h, followed by exposure to visible light for 5 min (400-550 nm, 5500 lx). Adhesion to human vascular endothelial cells or immobilized collagen was then evaluated. The influence of curcumin on chemotaxis and migration was also investigated, as well as curcumin induced alterations of α and β integrin expression. Curcumin without light exposure or light exposure without curcumin induced no alterations, whereas curcumin plus light significantly inhibited RCC adhesion, migration, and chemotaxis. This was associated with a distinct reduction of α3, α5, β1, and β3 integrins in all cell lines. Separate blocking of each of these integrin subtypes led to significant modification of tumor cell adhesion and chemotactic behavior. Combining low dosed curcumin with light considerably suppressed RCC binding activity and chemotactic movement and was associated with lowered integrin α and β subtypes. Therefore, curcumin combined with visible light holds promise for inhibiting metastatic processes in RCC.

Background: Organotypic tissue-cultured skin equivalents are used for a broad range of applications either as possible substitute for animal tests or for transplantation in patient-centered care. Aims: In this study, we implemented melanocytes in a tissue-cultured full-thickness skin equivalent, consisting of epidermis and dermis. The versatility of this skin-like model with respect to pigmentation and morphological criteria was tested. Materials and Methods: Pigmented skin equivalents were morphologically characterized, and melanogenesis was evaluated after treatment with kojic acid – a tyrosinase inhibitor and forskolin – a well-known activator of the cyclic adenosine 3,5-monophosphate pathway. Pigmentation was measured either by determination of the extinction at 400 nm after melanin extraction with KOH correlated to a melanin standard curve or by reflectance colorimetric analysis, monitoring reflectance of 660 nm and 880 nm emitting diodes. Results: The morphological analysis revealed characteristic epidermal stratification with melanocytes located at the basal layer. Stimulation with forskolin increased the pigmentation, whereas treatment with kojic acid caused bleaching. Conclusion: The present study demonstrates that the herein-introduced organotypic tissue-cultured skin equivalent is comparable to the normal human skin and its versatility in tests regarding skin pigmentation. Therefore, this model might help understand diseases with dysfunctional pigmentation such as melasma, vitiligo, and postinflammatory hyperpigmentation.

Curcumin—a rhizomal phytochemical from the plant Curcuma longa—is well known to inhibit cell proliferation and to induce apoptosis in a broad range of cell lines. In previous studies we showed that combining low curcumin concentrations and subsequent ultraviolet A radiation (UVA) or VIS irradiation induced anti-proliferative and pro-apoptotic effects. There is still debate whether curcumin induces apoptosis via the extrinsic or the intrinsic pathway. To address this question, we investigated in three epithelial cell lines (HaCaT, A431, A549) whether the death receptors CD95, tumor necrosis factor (TNF)-receptor I and II are involved in apoptosis induced by light and curcumin. Cells were incubated with 0.25–0.5 µg/mL curcumin followed by irradiation with 1 J/cm2 UVA. This treatment was combined with inhibitors specific for distinct membrane-bound death receptors. After 24 h apoptosis induction was monitored by quantitative determination of cytoplasmic histone-associated-DNA-fragments. Validation of our test system showed that apoptosis induced by CH11 and TNF-α could be completely inhibited by their respective antagonists. Interestingly, apoptosis induced by curcumin/light treatment was reversed by none of the herein examined death receptor antagonists. These results indicate a mechanism of action independent from classical death receptors speaking for intrinsic activation of apoptosis. It could be speculated that a shift in cellular redox balance might prompt the pro-apoptotic processes.

The anti-cancer properties of curcumin in vitro have been documented. However, its clinical use is limited due to rapid metabolization. Since irradiation of curcumin has been found to increase its anti-cancer effect on several tumor types, this investigation was designed to determine whether irradiation with visible light may enhance the anti-tumor effects of low-dosed curcumin on renal cell carcinoma (RCC) cell growth and proliferation. A498, Caki1, and KTCTL-26 cells were incubated with curcumin (0.1–0.4 µg/mL) and irradiated with 1.65 J/cm2 visible light for 5 min. Controls were exposed to curcumin or light alone or remained untreated. Curcumin plus light, but not curcumin or light exposure alone altered growth, proliferation, and apoptosis of all three RCC tumor cell lines. Cells were arrested in the G0/G1 phase of the cell cycle. Phosphorylated (p) CDK1 and pCDK2, along with their counter-receptors Cyclin B and A decreased, whereas p27 increased. Akt-mTOR-signaling was suppressed, the pro-apoptotic protein Bcl-2 became elevated, and the anti-apoptotic protein Bax diminished. H3 acetylation was elevated when cells were treated with curcumin plus light, pointing to an epigenetic mechanism. The present findings substantiate the potential of combining low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in RCC.

The natural compound curcumin exerts antitumor properties in vitro, but its clinical application is limited due to low bioavailability. Light exposure in skin and skin cancer cells has been shown to improve curcumin bioavailability; thus, the object of this investigation was to determine whether light exposure might also enhance curcumin efficacy in bladder cancer cell lines. RT112, UMUC3, and TCCSUP cells were preincubated with low curcumin concentrations (0.1-0.4 μg/ml) and then exposed to 1.65 J/cm2 visible light for 5 min. Cell growth, cell proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins along with acetylation of histone H3 and H4 were investigated. Though curcumin alone did not alter cell proliferation or apoptosis, tumor cell growth and proliferation were strongly blocked when curcumin was combined with visible light. Curcumin-light caused the bladder cancer cells to become arrested in different cell phases: G0/G1 for RT112, G2/M for TCCSUP, and G2/M- and S-phase for UMUC3. Proteins of the Cdk-cyclin axis were diminished in RT112 after application of 0.1 and 0.4 μg/ml curcumin. Cell cycling proteins were upregulated in TCCSUP and UMUC3 in the presence of 0.1 μg/ml curcumin-light but were partially downregulated with 0.4 μg/ml curcumin. 0.4 μg/ml (but not 0.1 μg/ml) curcumin-light also evoked late apoptosis in TCCSUP and UMUC3 cells. H3 and H4 acetylation was found in UMUC3 cells treated with 0.4 μg/ml curcumin alone or with 0.1 μg/ml curcumin-light, pointing to an epigenetic mechanism. Light exposure enhanced the antitumor potential of curcumin on bladder cancer cells but by different molecular action modes in the different cell lines. Further studies are necessary to evaluate whether intravesical curcumin application, combined with visible light, might become an innovative tool in combating bladder cancer.

OBJECTIVE Although the natural compound curcumin exerts antitumor properties in vitro, its clinical application is hampered due to rapid metabolism. Light exposure following curcumin application has been demonstrated to improve curcumin's bioavailability. Therefore, this investigation was directed towards evaluating whether light exposure in addition to curcumin application enhances curcumin's efficacy against bladder cancer cell adhesion and migration. MATERIALS AND METHODS RT112, UMUC3, and TCCSUP cells were incubated with low curcumin concentrations (0.1-0.4 μg/ml) and then exposed to 1.65 J/cm2 visible light for 5 min. Controls remained untreated or were treated with curcumin or light alone. Cell adhesion to Human umbilical vein endothelial cells (HUVECs), to immobilized collagen or fibronectin and chemotactic behavior, integrin α and β receptor expression with functional relevance, as well as focal adhesion kinase (total and phosphorylated FAK) were evaluated. RESULTS Curcumin plus light, but neither curcumin nor light alone, significantly altered tumor cell adhesion and suppressed chemotaxis. Integrin α and β subtypes were dissimilarly modified, depending on the cell line. Suppression of pFAK was noted in RT112 and UMUC3, but not in TCCSUP cells. The integrins α3, α5, and β1 were involved in curcumin's regulation of adhesion and migration. Blocking studies revealed α3, α5, and β1 to be associated with TCCSUP adhesion and migration, whereas α5 and β1, but not α3 contributed to UMUC3 adhesion and migration. Integrin α5 and β1 controlled RT112 chemotaxis as well, but only α5 was involved in the RT112 adhesion process. CONCLUSIONS Combining curcumin with light exposure enhances curcumin's anti-tumor potential.

Photodermatology, Photoimmunology & PhotomedicineVolume 34, Issue 4 p. 279-283 LETTER TO THE EDITOR Effect of near-infrared photobiomodulation therapy in a cellular wound healing model Anke König, Anke König Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorSvenja Missalla, Svenja Missalla Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorEva M. Valesky, Eva M. Valesky Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorAugust Bernd, August Bernd Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorRoland Kaufmann, Roland Kaufmann Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorStefan Kippenberger, Stefan Kippenberger Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorNadja N. Zöller, Corresponding Author Nadja N. Zöller nadja.zoeller@kgu.de orcid.org/0000-0003-2438-2747 Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, Germany Correspondence Nadja N. Zöller, Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. Email: nadja.zoeller@kgu.deSearch for more papers by this author Anke König, Anke König Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorSvenja Missalla, Svenja Missalla Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorEva M. Valesky, Eva M. Valesky Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorAugust Bernd, August Bernd Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorRoland Kaufmann, Roland Kaufmann Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorStefan Kippenberger, Stefan Kippenberger Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, GermanySearch for more papers by this authorNadja N. Zöller, Corresponding Author Nadja N. Zöller nadja.zoeller@kgu.de orcid.org/0000-0003-2438-2747 Department of Dermatology, Venereology and Allergology, Medical School, Goethe-University, Frankfurt am Main, Germany Correspondence Nadja N. Zöller, Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. Email: nadja.zoeller@kgu.deSearch for more papers by this author First published: 26 April 2018 https://doi.org/10.1111/phpp.12390Citations: 1 König and Missalla contributed equally. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Supporting Information Filename Description phpp12390-sup-0001-FigS1.TIFimage/tif, 267.7 KB phpp12390-sup-0002-TableS1.docxWord document, 15.9 KB Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume34, Issue4July 2018Pages 279-283 RelatedInformation

Ionizing and near-infrared radiation are both part of the therapeutic spectrum in cancer treatment. During cancer therapy ionizing radiation is typically used for non-invasive reduction of malignant tissue, while near infrared photobiomodulation is utilized in palliative medical approaches, e.g. for pain reduction or impairment of wound healing. Furthermore, near-infrared is part of the solar wavelength spectrum. A combined exposure of these two irradiation qualities either intentionally during medical treatment or unintentionally due to solar exposure is therefore presumable for cancer patients. Several studies in different model organisms and cell cultures show a strong impact of near-infrared pretreatment on ionizing radiation-induced stress response. To investigate the risks of non-thermal near-infrared (NIR) pretreatment in patients, a human in vitro full thickness skin models (FTSM) was evaluated for radiation research. FTSM were pretreated with therapy-relevant doses of NIR followed by X-radiation, and then examined for DNA-double-strand break (DSB) repair, cell proliferation and apoptosis. Double-treated FTSM revealed a clear influence of NIR on X-radiation-induced stress responses in cells in their typical tissue environment. Furthermore, over a 24 h time period, double-treated FTSM presented a significant persistence of DSBs, as compared to samples exclusively irradiated by X-rays. In addition, NIR pretreatment inhibited apoptosis induction of integrated fibroblasts, and counteracted the radiation-induced proliferation inhibition of basal keratinocytes. Our work suggests that cancer patients treated with X-rays should be prevented from uncontrolled NIR irradiation. On the other hand, controlled double-treatment could provide an alternative therapy approach, exposing the patient to less radiation.

Objective: Curcumin is known for its anti-oxidative, anti-inflammatory and anti-tumorigenic qualities at concentrations ranging from 3.7µg/ml to 55µg/ml. Therefore it is pre-destined for tumour therapy. Due to high oral doses that have to be administered and the low bioavailability of curcumin new therapy concepts have to be developed. One of these therapy concepts is the combination of low curcumin concentrations and UVA or visible light. Aim of our study was to investigate the influence of this treatment regime on oral squamous cell carcinoma cells. Materials and Methods: A human oral squamous cell carcinoma cell line (HN) was pre-incubated with low curcumin concentrations (0.01µg/ml to 1µg/ml). Thereafter cell cultures were either left un-irradiated or were irradiated either with 1J/cm2 UVA or for 5min with visible light. Quantitative analysis of proliferation, membrane integrity, oxidative potential and DNA fragmentation were done. Results: It could be shown that low curcumin concentrations neither influenced proliferation, nor cell morphology, nor cell integrity nor apoptosis. When combining these curcumin concentrations with UVA or visible light irradiation cell proliferation as well as development of reactive oxygen species was reduced whereas DNA fragmentation was increased. Concentration as well as light entity specific effects could be observed. Conclusions: The present findings substantiate the potential of the combination of low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer of the oral mucosa.

Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values.

Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.

Hypertrophic scar development is associated to impaired wound healing, imbalanced fibroblast proliferation and extracellular matrix synthesis. Stigmatization, physical restrictions and high recurrence rates are only some aspects that illustrate the severe influence impaired wound healing can have on patients' life. The treatment of hypertrophic scars especially keloids is still a challenge. In recent years water-filtered near-infrared irradiation (wIRA) composed of near-infrared (NIR) and a thermal component is applied for an increasing penal of clinical purposes. It is described to beneficially influence e.g. wound healing. But discrimination between the thermal and the NIR dependent components of these effects has not been conclusively elucidated. Aim of our study was therefore to investigate the influence of the light fraction on the thermal impact of wIRA irradiation in dermal cells. We concentrated our analysis on morphological properties and collagen synthesis. Foreskin fibroblasts and the keloid fibroblast cell line KF111 were exposed to temperatures between 37°C and 46°C with or without additional irradiation with 360J/cm(2) NIR. Our results show that viability was not influenced by irradiation. Independent of the analysed fibroblast species temperature dependent occurrence of spheric cells could be observed. These morphological changes were clearly counteracted by additional light exposure. Convective heat reduced collagen type I synthesis in both cell species depending on the applied temperature. Co-treatment with NIR significantly reversed this effect in keloid fibroblast cultures treated at 46°C whereas no difference could be observed in the foreskin fibroblasts. The observed influence on collagen type I synthesis was associated to a temperature dependent TGF-β1 secretion reduction. Co-stimulation of keloid cultures with NIR at 46°C completely abolished the temperature dependent TGF-β1 secretion reduction. In foreskin fibroblast cultures co-treatment with NIR had no additional influence on TGF-β1 secretion. The observed influence of convective heat treatment with and without NIR on keloid and foreskin fibroblasts indicates a possible clinical application that has to be evaluated in further basic research and clinical studies in context of hypertrophic scar treatment.

The Journal of DermatologyVolume 44, Issue 10 p. 1177-1178 Letter to the Editor Efficiency and safety of a Curcuma extract combined with visible blue light phototherapy on adults with plaque psoriasis: A phase IV, randomized, open pilot clinical trial Ana Ramírez-Boscá, Ana Ramírez-Boscá Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, Spain Department of Medicine, Saint Anthony Catholic University, Murcia, SpainSearch for more papers by this authorVicente Navarro-López, Vicente Navarro-López Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, Spain Department of Medicine, Saint Anthony Catholic University, Murcia, SpainSearch for more papers by this authorMiguel Carrión-Gutiérrez, Corresponding Author Miguel Carrión-Gutiérrez mcarrion@asac.net orcid.org/0000-0002-8260-8399 Clinical Research Unit, Especialidades Farmacéuticas Centrum, Alicante, SpainCorrespondence: Miguel Carrión-Gutiérrez, Ph.D., Especialidades Farmacéuticas Centrum, Calle Sagitario, 14, 03006 Alicante, Spain. Email: mcarrion@asac.netSearch for more papers by this authorAsunción Martínez-Andrés, Asunción Martínez-Andrés Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, SpainSearch for more papers by this authorJuan José Vilata-Corell, Juan José Vilata-Corell Department of Dermatology, Hospital General Universitario de Valencia, Valencia, SpainSearch for more papers by this authorManuel Asín-Llorca, Manuel Asín-Llorca Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, SpainSearch for more papers by this authorJosé Francisco Horga de la Calle, José Francisco Horga de la Calle Department of Pharmacology, Pediatrics and Organic Chemistry, Miguel Hernández University, Elche, SpainSearch for more papers by this authorAugust Bernd, August Bernd Department of Dermatology, Venereology and Alergology, J.W. Goethe-University, Medical School, Frankfurt/Main, GermanySearch for more papers by this author Ana Ramírez-Boscá, Ana Ramírez-Boscá Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, Spain Department of Medicine, Saint Anthony Catholic University, Murcia, SpainSearch for more papers by this authorVicente Navarro-López, Vicente Navarro-López Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, Spain Department of Medicine, Saint Anthony Catholic University, Murcia, SpainSearch for more papers by this authorMiguel Carrión-Gutiérrez, Corresponding Author Miguel Carrión-Gutiérrez mcarrion@asac.net orcid.org/0000-0002-8260-8399 Clinical Research Unit, Especialidades Farmacéuticas Centrum, Alicante, SpainCorrespondence: Miguel Carrión-Gutiérrez, Ph.D., Especialidades Farmacéuticas Centrum, Calle Sagitario, 14, 03006 Alicante, Spain. Email: mcarrion@asac.netSearch for more papers by this authorAsunción Martínez-Andrés, Asunción Martínez-Andrés Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, SpainSearch for more papers by this authorJuan José Vilata-Corell, Juan José Vilata-Corell Department of Dermatology, Hospital General Universitario de Valencia, Valencia, SpainSearch for more papers by this authorManuel Asín-Llorca, Manuel Asín-Llorca Department of Dermatology and Clinical Research Units, Centro Dermatológico Estético, Alicante, SpainSearch for more papers by this authorJosé Francisco Horga de la Calle, José Francisco Horga de la Calle Department of Pharmacology, Pediatrics and Organic Chemistry, Miguel Hernández University, Elche, SpainSearch for more papers by this authorAugust Bernd, August Bernd Department of Dermatology, Venereology and Alergology, J.W. Goethe-University, Medical School, Frankfurt/Main, GermanySearch for more papers by this author First published: 28 October 2016 https://doi.org/10.1111/1346-8138.13668Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume44, Issue10October 2017Pages 1177-1178 RelatedInformation

To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus, the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404.

INTRODUCTION:We conducted a phase IV randomized, double-blind, placebo-controlled, pilot clinical trial to investigate the safety and efficacy of oral curcumin together with local phototherapy in patients with plaque psoriasis.MATERIALS AND METHODS:Patients with moderate to severe psoriasis received Curcuma extract orally with real visible light phototherapy (VLRT) or simulated visible light phototherapy (VLST) in the experimental area, while the rest of the body surface was treated with ultraviolet A (UVA) radiation. The endpoints were the number of responders and the temporal course of the response. The secondary outcomes were related to safety and adverse events.RESULTS:Twenty-one patients were included in the study. In the intention-to-treat analysis, no patients included in the VLRT group showed "moderate" or "severe" plaques after the treatment, in contrast to the patients included in the VSLT group (p<0.01). Parallelisms in the evolution of PGA, BSA, and PASI scores were observed in the two groups following the treatment. At the end of the study period, 76% of all patients showed a response in the BSA exposed to UVA. Lesions on the experimental area showed a response in 81% of the patients in the VLRT group and 30% of the patients in the VLST group. There were no study-related adverse events that necessitated participant withdrawal.CONCLUSION:The results suggested that moderate to severe plaque psoriasis should show a therapeutic response to orally administered Curcuma if activated with visible light phototherapy, a new therapeutic method that would be safer for patients than existing treatments.