- Email: [email protected]
581 Nutritional supplement improves skin health
Photobiology | ABSTRACTS 579
580
Posaconazole substitution for voriconazole-associated photocarcinogenesis A Jacobsen1, Y Papo2, R Sarro2, K Weisse2 and J Strasswimmer2 1 University of Miami Miller School of Medicine, Miami, FL and 2 Internal Medicine Residency Program, Florida Atlantic University, Boca Raton, FL An alternative for voriconazole-induced photocarcinogenesis for at-risk patients has not been well studied. Here we present a patient who has been successfully treated with posaconazole after developing severe voriconazole-induced photocarcinogenesis. An elderly light-skinned female had been receiving voriconazole and low-dose corticosteroids for suppression of chronic Exophiala dermatitidis meningitis for the last 5 years. She had no history of hematologic malignancy, solid organ transplantation or other immunosuppressed state. Several months after starting voriconazole, the patient developed a severe photosensitivity reaction, which progressed to extensive actinic keratosis (AK) development. The patient subsequently required 3 Mohs surgeries for large, aggressive squamous cell carcinomas (SCC) on her extremities, had 348 AKs treated, and 32 of 41 biopsies positive for SCC over 21 months. We compared the number of AKs treated during six months preceding the switch with a six-month period after, allowing for a “transition” time in between. AKs trended down, decreasing from 22.2 (SD¼13.0) to 6.6 (SD¼8.2) and no subsequent Mohs surgery was required. Treatment options for Exophiala dermatitidis, a dematiaceous fungi with melaninlike pigment in the cell wall, are not well documented, but voriconazole is widely used for treatment and prophylaxis of fungal infections. However, approximately 8-10% of patients experience dermatologic side effects including phototoxicity, new-onset squamous cell carcinoma, pseudoporphyria, discoid lupus erythematosus, and accelerated photoaging. These adverse events have not been reported with posaconazole and a recent meta-analysis ranked posaconazole superior to voriconazole in preventing invasive fungal infections (Zhao et al. 2015). Considering that posaconazole has a favorable side effect profile and has shown good efficacy in invasive fungal infection prophylaxis and treatment, it should be considered more often as a first line drug in at-risk patients.
Topical application of ST266 reduces UV-induced skin damage E Galan1,2, L Guan1, A Suggs1,2, M Lam1 and E Baron1,2,3 1 Derm, Case Western Reserve Univ, Cleveland, OH, 2 Univ Hosp Case Med Ctr, Cleveland, OH and 3 VA Med Ctr, Cleveland, OH ST266 is a novel secretome from proprietary cells. Pre-clinical animal studies show that ST266 reduces inflammation by inhibiting pro-inflammatory cytokines (IFN-g, TNF-a, IL-1b, and IL-2) and accelerates wound healing by promoting cell migration. We postulated that ST266 could also be used to decrease the inflammation and DNA damage associated with UV exposure. To evaluate the acute effects of ST266 on human skin exposed to UVR, gluteal skin of 10 healthy volunteers was exposed to a 2 minimum erythema dose (MED) of simulated solar radiation (SSR). The SSR exposed skin was subsequently treated with ST266 immediately, treated with ST266 following an 8-12 hour delay, or left as an untreated control site. ST266 was applied twice daily for 3 days. Each test site was then assessed for erythema compared to unirradiated skin at 24-36, 48 and 72 hours post SSR. Biopsy of irradiated skin was done at 24-36 hours post SSR for evaluation of Xeroderma pigmentosum complementation group A (XPA) protein expression and cyclobutane pyrimidine dimer formation (CPD). XPA is an enzyme implicated in DNA repair and CPD is a marker for DNA damage. At 24-36 hours post SSR, irradiated skin treated with ST266 promptly after irradiation had significantly less erythema than untreated, irradiated skin (p¼ 0.00079). The anti-erythema effect was not observed in sites that had delayed ST266 treatment. Similar findings were observed at the 48 hour and 72 hour time points. Immunohistochemistry staining of biopsy samples taken at 2436 hours revealed marginally significant lower CPD levels with immediate ST266 treatment when compared with irradiated, untreated controls (p¼ 0.05). However, XPA expression levels were not statistically significant (p¼ 0.55). In conclusion, ST266 shows potential as a treatment for UV-induced erythema and CPD clearance when applied immediately after UV exposure.
581
582
Nutritional supplement improves skin health S Wood1, R Gray1, S Hester1, A Mastaloudis1, D Kern1, J Namkoong1 and ZD Draelos2 1 Nu Skin Enterprises, Inc., Provo, UT and 2 Dermatology Consulting Services, High Point, NC Topical skin care products are used to improve skin health by keeping skin moisturized, protected from sun damage, and supporting skin recovery. In addition to applying topical products, skin health can be enhanced by eating a healthier diet or taking nutritional supplements. Nutritional supplements containing fish oil, vitamin K2 and D, alpha-lipoic acid, co-enzyme Q10, quercetin, citrus bioflavonoids (naringin and hesperidin), d-limonene, resveratrol, carotenoids (lycopene, lutein and astaxanthin), purple corn extract and rosemary extracts were specially developed to boost aging defense mechanisms (ADMs), which protect and repair cellular functions. In order to assess benefits to the skin in particular, a clinical study was designed with 40 subjects to evaluate facial efficacy and photoprotection capacity. Non-smoking subjects with Fitzpatrick skin types I and II were recruited. A solar simulator was used in the assessment of the photoprotection capacity of the nutritional supplement. Small sun-protected areas of study subject skin was irradiated with three UV doses, 1 minimal erythemal dose (MED), 2MED and 3MED. Erythema was measured by a dermospectrophotometer, with non-irradiated skin as a control. After 8 weeks of supplementation, there was a statistically significant decrease in skin erythema, while there was no change in the nonirradiated skin. 8 weeks of supplementation also improved facial skin radiance, texture and overall appearance with statistical significance, measured by dermatological evaluations. In addition to dermatological assessments, subjects self-evaluated their skin. By self-assessment, subjects felt their skin firmness was improved and that was confirmed by measuring skin elasticity with a cutometer. This study suggests that a well-designed nutritional supplement can improve the skin from within.
Potent self-delivering rnai compounds targeting MMP1 reduce UVR induced MMP1 upregulation K Holton, M Maxwell, J Cardia, R Looby, M Byrne and K Bulock RXi Pharmaceuticals, Marlborough, MA The extracellular matrix (ECM) is a dynamic scaffold primarily comprised of collagens and proteoglycans that supplies structural and biochemical support to cells and tissue. The ECM is involved in cell adhesion, growth, apoptosis and cell-to-cell signaling. Tight regulation of the ECM is critical to the viability and proper functioning of its associated cells and the entire tissue system it comprises. Solar ultraviolet irradiation (UVR), specifically UVA and UVB irradiation, are the causative factors for sunlight induced photo-aging of the skin. One of the key players in this phenomenon is the collagenase known as matrix metalloproteinase I (MMP1), the enzyme responsible for the degradation of Collagen 1, the main component of skin ECM. MMPs are a family of proteins whose primary function is to regulate the components of the ECM. Up-regulation of members of the MMP family results in degradation of ECM and has been implicated in the pathogenesis of many diseases as well as skin aging. UVR exposure induces an overexpression of MMP1 by skin fibroblasts and keratinocytes which contributes substantially to connective tissue damage resulting in severe collagen deficiency and wrinkling during photo-aging. Additionally, the overexpression of MMP1 has been associated with tumorigenesis and metastasis in many cancer types, including melanoma. For these reasons, MMP1 is an attractive target for RNAi gene silencing. Self-delivering rxRNA (sd-rxRNAÒ) is a proprietary platform of RNAi compounds that demonstrate potent activity, stability, and reduced immune stimulation and are rapidly and efficiently taken up by cells without the requirement of a transfection reagent or a delivery vehicle. We have identified RXI-185, a potent sd-rxRNA targeting MMP1 capable of reducing MMP1 mRNA and enzyme activity levels in an in vitro 3D skin model system after exposure to skin damaging levels of UVR. Blocking the UVR-induced MMP1 overexpression with RXI-185 may lessen the effects of photo-aging on the skin. An update on our path toward cosmeceutical development will be provided.
583
584
Wavelength characteristics of UVA1 therapy for scleroderma H Masuda1,2, M Kimura1,2 and A Morita1 1 Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan and 2 Ushio Inc., Tokyo, Japan UVA1 phototherapy selectively uses the longer-wavelength UVA1 light of 340nm to 400nm and does not use the shorter-wavelength UVA2 (320-340 nm) or UVB wavelengths (290-320 nm) that cause an erythema reaction. Several studies have reported the effectiveness of UVA1 therapy for diseases in which T cells infiltrate the dermis and excessive collagen accumulates, such as atopic dermatitis, T-cell lymphoma, and systemic sclerosis. The wavelength specificity within the UVA1 range, however, has not been clarified. Although metal-halide lamps are commonly used as the light source for UVA1 therapy due to their high intensity, they are not efficient because of their a broad spectrum, ranging from w200 nm to 500 nm, and three filters are needed to remove the unnecessary wavelengths. Therefore, we investigated the wavelength characteristics of the AlGaN and InGaN system light-emitting diodes (LED) to develop a more effective and efficient UVA1 delivery system. Fibroblast cells were irradiated with monochrome UVA1 light using UV-LEDs. After irradiation, the cells were incubated and matrix metalloproteinase-1 (MMP-1) RNA expression was measured using the real-time polymerase chain reaction. Our findings indicated that MMP-1 was significantly increased by irradiation in the UVA1 wavelength region. These findings indicate that UV-LEDs are a promising light source for UVA1 phototherapy machines.
Role of UVB-induced, IL-1 in dermal collagen alteration in murine skin M Sharma1,2, R Mitrani1,2 and VP Werth1,2 1 Corporal Michael J. Crescenz Medical Center, Philadelphia, PA and 2 Dermatology, University of Pennsylvania, Philadelphia, PA UVB induces many pro-inflammatory cytokines, including IL-1a and the influx of inflammatory cells, especially neutrophils, in the dermis. We evaluated the role of IL-1 with acute and chronic exposure of UVB in altering collagen in the dermis. We used IL-1ra transgenic mice (B6.CBA-Tg (Il1rn)1Dih/J). WT and TG mice were irradiated with short term UVB (100 mJ/cm2/day for 5 days) and chronic UVB (1 month) [100 mJ/cm2/day 3 times/week (week 1), then 200mJ/cm2/day 3 times/week (weeks 2-4), with a total dose of 2100 mJ/cm2]. We assayed the epidermal and dermal thickness, neutrophil number, MMP-13 protein, and collagen fiber integrity. Skin sections were stained with picrosirius red to visualize collagen fibers under circular polarized light microscopy. Polarized light differentiates collagen fibers as red or yellow (mature thick fibers) and green (thin). Our data showed a significant decrease in neutrophils (p< 0.001) and MMP-13 levels (p< 0.001) in the epidermis of TG UVB mice as compared to WT UVB after both short term and chronic UVB exposure. The neutrophil and MMP-13 levels were 40-50% less in TG and WT chronic UVB irradiated mice as compared to short term UVB (p<0.01). Wild type sham, TG sham and TG UVB-irradiated mice had the same percentage of red collagen. The percentage of red collagen in short term UVB-irradiated WT mice decreased relative to UVB-irradiated TG mice (742 vs 842, p<0.01). In WT UVB, green fibers were increased as compared to sham (222 vs 91.2, p<0.001). WT UVB showed a higher percentage of green fibers than TG UVB-irradiated mice (222 vs 121.7, p<0.01). In long-term UVB-irradiated mice there was a decrease in percentage of red color collagen fibers and an increase in green color collagen in both WT and TG mice. It is likely that a non-IL-1 mechanism is responsible for collagen degradation in chronically irradiated skin. Our data suggests that IL-1 plays a significant role in collagen changes in the dermis only in short term UVB-irradiated skin.
www.jidonline.org S103
580
Posaconazole substitution for voriconazole-associated photocarcinogenesis A Jacobsen1, Y Papo2, R Sarro2, K Weisse2 and J Strasswimmer2 1 University of Miami Miller School of Medicine, Miami, FL and 2 Internal Medicine Residency Program, Florida Atlantic University, Boca Raton, FL An alternative for voriconazole-induced photocarcinogenesis for at-risk patients has not been well studied. Here we present a patient who has been successfully treated with posaconazole after developing severe voriconazole-induced photocarcinogenesis. An elderly light-skinned female had been receiving voriconazole and low-dose corticosteroids for suppression of chronic Exophiala dermatitidis meningitis for the last 5 years. She had no history of hematologic malignancy, solid organ transplantation or other immunosuppressed state. Several months after starting voriconazole, the patient developed a severe photosensitivity reaction, which progressed to extensive actinic keratosis (AK) development. The patient subsequently required 3 Mohs surgeries for large, aggressive squamous cell carcinomas (SCC) on her extremities, had 348 AKs treated, and 32 of 41 biopsies positive for SCC over 21 months. We compared the number of AKs treated during six months preceding the switch with a six-month period after, allowing for a “transition” time in between. AKs trended down, decreasing from 22.2 (SD¼13.0) to 6.6 (SD¼8.2) and no subsequent Mohs surgery was required. Treatment options for Exophiala dermatitidis, a dematiaceous fungi with melaninlike pigment in the cell wall, are not well documented, but voriconazole is widely used for treatment and prophylaxis of fungal infections. However, approximately 8-10% of patients experience dermatologic side effects including phototoxicity, new-onset squamous cell carcinoma, pseudoporphyria, discoid lupus erythematosus, and accelerated photoaging. These adverse events have not been reported with posaconazole and a recent meta-analysis ranked posaconazole superior to voriconazole in preventing invasive fungal infections (Zhao et al. 2015). Considering that posaconazole has a favorable side effect profile and has shown good efficacy in invasive fungal infection prophylaxis and treatment, it should be considered more often as a first line drug in at-risk patients.
Topical application of ST266 reduces UV-induced skin damage E Galan1,2, L Guan1, A Suggs1,2, M Lam1 and E Baron1,2,3 1 Derm, Case Western Reserve Univ, Cleveland, OH, 2 Univ Hosp Case Med Ctr, Cleveland, OH and 3 VA Med Ctr, Cleveland, OH ST266 is a novel secretome from proprietary cells. Pre-clinical animal studies show that ST266 reduces inflammation by inhibiting pro-inflammatory cytokines (IFN-g, TNF-a, IL-1b, and IL-2) and accelerates wound healing by promoting cell migration. We postulated that ST266 could also be used to decrease the inflammation and DNA damage associated with UV exposure. To evaluate the acute effects of ST266 on human skin exposed to UVR, gluteal skin of 10 healthy volunteers was exposed to a 2 minimum erythema dose (MED) of simulated solar radiation (SSR). The SSR exposed skin was subsequently treated with ST266 immediately, treated with ST266 following an 8-12 hour delay, or left as an untreated control site. ST266 was applied twice daily for 3 days. Each test site was then assessed for erythema compared to unirradiated skin at 24-36, 48 and 72 hours post SSR. Biopsy of irradiated skin was done at 24-36 hours post SSR for evaluation of Xeroderma pigmentosum complementation group A (XPA) protein expression and cyclobutane pyrimidine dimer formation (CPD). XPA is an enzyme implicated in DNA repair and CPD is a marker for DNA damage. At 24-36 hours post SSR, irradiated skin treated with ST266 promptly after irradiation had significantly less erythema than untreated, irradiated skin (p¼ 0.00079). The anti-erythema effect was not observed in sites that had delayed ST266 treatment. Similar findings were observed at the 48 hour and 72 hour time points. Immunohistochemistry staining of biopsy samples taken at 2436 hours revealed marginally significant lower CPD levels with immediate ST266 treatment when compared with irradiated, untreated controls (p¼ 0.05). However, XPA expression levels were not statistically significant (p¼ 0.55). In conclusion, ST266 shows potential as a treatment for UV-induced erythema and CPD clearance when applied immediately after UV exposure.
581
582
Nutritional supplement improves skin health S Wood1, R Gray1, S Hester1, A Mastaloudis1, D Kern1, J Namkoong1 and ZD Draelos2 1 Nu Skin Enterprises, Inc., Provo, UT and 2 Dermatology Consulting Services, High Point, NC Topical skin care products are used to improve skin health by keeping skin moisturized, protected from sun damage, and supporting skin recovery. In addition to applying topical products, skin health can be enhanced by eating a healthier diet or taking nutritional supplements. Nutritional supplements containing fish oil, vitamin K2 and D, alpha-lipoic acid, co-enzyme Q10, quercetin, citrus bioflavonoids (naringin and hesperidin), d-limonene, resveratrol, carotenoids (lycopene, lutein and astaxanthin), purple corn extract and rosemary extracts were specially developed to boost aging defense mechanisms (ADMs), which protect and repair cellular functions. In order to assess benefits to the skin in particular, a clinical study was designed with 40 subjects to evaluate facial efficacy and photoprotection capacity. Non-smoking subjects with Fitzpatrick skin types I and II were recruited. A solar simulator was used in the assessment of the photoprotection capacity of the nutritional supplement. Small sun-protected areas of study subject skin was irradiated with three UV doses, 1 minimal erythemal dose (MED), 2MED and 3MED. Erythema was measured by a dermospectrophotometer, with non-irradiated skin as a control. After 8 weeks of supplementation, there was a statistically significant decrease in skin erythema, while there was no change in the nonirradiated skin. 8 weeks of supplementation also improved facial skin radiance, texture and overall appearance with statistical significance, measured by dermatological evaluations. In addition to dermatological assessments, subjects self-evaluated their skin. By self-assessment, subjects felt their skin firmness was improved and that was confirmed by measuring skin elasticity with a cutometer. This study suggests that a well-designed nutritional supplement can improve the skin from within.
Potent self-delivering rnai compounds targeting MMP1 reduce UVR induced MMP1 upregulation K Holton, M Maxwell, J Cardia, R Looby, M Byrne and K Bulock RXi Pharmaceuticals, Marlborough, MA The extracellular matrix (ECM) is a dynamic scaffold primarily comprised of collagens and proteoglycans that supplies structural and biochemical support to cells and tissue. The ECM is involved in cell adhesion, growth, apoptosis and cell-to-cell signaling. Tight regulation of the ECM is critical to the viability and proper functioning of its associated cells and the entire tissue system it comprises. Solar ultraviolet irradiation (UVR), specifically UVA and UVB irradiation, are the causative factors for sunlight induced photo-aging of the skin. One of the key players in this phenomenon is the collagenase known as matrix metalloproteinase I (MMP1), the enzyme responsible for the degradation of Collagen 1, the main component of skin ECM. MMPs are a family of proteins whose primary function is to regulate the components of the ECM. Up-regulation of members of the MMP family results in degradation of ECM and has been implicated in the pathogenesis of many diseases as well as skin aging. UVR exposure induces an overexpression of MMP1 by skin fibroblasts and keratinocytes which contributes substantially to connective tissue damage resulting in severe collagen deficiency and wrinkling during photo-aging. Additionally, the overexpression of MMP1 has been associated with tumorigenesis and metastasis in many cancer types, including melanoma. For these reasons, MMP1 is an attractive target for RNAi gene silencing. Self-delivering rxRNA (sd-rxRNAÒ) is a proprietary platform of RNAi compounds that demonstrate potent activity, stability, and reduced immune stimulation and are rapidly and efficiently taken up by cells without the requirement of a transfection reagent or a delivery vehicle. We have identified RXI-185, a potent sd-rxRNA targeting MMP1 capable of reducing MMP1 mRNA and enzyme activity levels in an in vitro 3D skin model system after exposure to skin damaging levels of UVR. Blocking the UVR-induced MMP1 overexpression with RXI-185 may lessen the effects of photo-aging on the skin. An update on our path toward cosmeceutical development will be provided.
583
584
Wavelength characteristics of UVA1 therapy for scleroderma H Masuda1,2, M Kimura1,2 and A Morita1 1 Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan and 2 Ushio Inc., Tokyo, Japan UVA1 phototherapy selectively uses the longer-wavelength UVA1 light of 340nm to 400nm and does not use the shorter-wavelength UVA2 (320-340 nm) or UVB wavelengths (290-320 nm) that cause an erythema reaction. Several studies have reported the effectiveness of UVA1 therapy for diseases in which T cells infiltrate the dermis and excessive collagen accumulates, such as atopic dermatitis, T-cell lymphoma, and systemic sclerosis. The wavelength specificity within the UVA1 range, however, has not been clarified. Although metal-halide lamps are commonly used as the light source for UVA1 therapy due to their high intensity, they are not efficient because of their a broad spectrum, ranging from w200 nm to 500 nm, and three filters are needed to remove the unnecessary wavelengths. Therefore, we investigated the wavelength characteristics of the AlGaN and InGaN system light-emitting diodes (LED) to develop a more effective and efficient UVA1 delivery system. Fibroblast cells were irradiated with monochrome UVA1 light using UV-LEDs. After irradiation, the cells were incubated and matrix metalloproteinase-1 (MMP-1) RNA expression was measured using the real-time polymerase chain reaction. Our findings indicated that MMP-1 was significantly increased by irradiation in the UVA1 wavelength region. These findings indicate that UV-LEDs are a promising light source for UVA1 phototherapy machines.
Role of UVB-induced, IL-1 in dermal collagen alteration in murine skin M Sharma1,2, R Mitrani1,2 and VP Werth1,2 1 Corporal Michael J. Crescenz Medical Center, Philadelphia, PA and 2 Dermatology, University of Pennsylvania, Philadelphia, PA UVB induces many pro-inflammatory cytokines, including IL-1a and the influx of inflammatory cells, especially neutrophils, in the dermis. We evaluated the role of IL-1 with acute and chronic exposure of UVB in altering collagen in the dermis. We used IL-1ra transgenic mice (B6.CBA-Tg (Il1rn)1Dih/J). WT and TG mice were irradiated with short term UVB (100 mJ/cm2/day for 5 days) and chronic UVB (1 month) [100 mJ/cm2/day 3 times/week (week 1), then 200mJ/cm2/day 3 times/week (weeks 2-4), with a total dose of 2100 mJ/cm2]. We assayed the epidermal and dermal thickness, neutrophil number, MMP-13 protein, and collagen fiber integrity. Skin sections were stained with picrosirius red to visualize collagen fibers under circular polarized light microscopy. Polarized light differentiates collagen fibers as red or yellow (mature thick fibers) and green (thin). Our data showed a significant decrease in neutrophils (p< 0.001) and MMP-13 levels (p< 0.001) in the epidermis of TG UVB mice as compared to WT UVB after both short term and chronic UVB exposure. The neutrophil and MMP-13 levels were 40-50% less in TG and WT chronic UVB irradiated mice as compared to short term UVB (p<0.01). Wild type sham, TG sham and TG UVB-irradiated mice had the same percentage of red collagen. The percentage of red collagen in short term UVB-irradiated WT mice decreased relative to UVB-irradiated TG mice (742 vs 842, p<0.01). In WT UVB, green fibers were increased as compared to sham (222 vs 91.2, p<0.001). WT UVB showed a higher percentage of green fibers than TG UVB-irradiated mice (222 vs 121.7, p<0.01). In long-term UVB-irradiated mice there was a decrease in percentage of red color collagen fibers and an increase in green color collagen in both WT and TG mice. It is likely that a non-IL-1 mechanism is responsible for collagen degradation in chronically irradiated skin. Our data suggests that IL-1 plays a significant role in collagen changes in the dermis only in short term UVB-irradiated skin.
www.jidonline.org S103