%0 Journal Article %~ PubMed %A Thanos, S M %A Halliday, G M %A Damian, D L %T Nicotinamide Reduces Photodynamic Therapy-Induced Immunosuppression In Humans. %B British Journal of Dermatology %D 2012 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 167 %N 3 %P 631-636 %@ 1365-2133 %X Background:??? The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B3) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. Objectives:??? We aimed to determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. Methods:??? Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500mg oral nicotinamide or placebo twice daily for 1 week in a randomised, double-blinded, cross-over design. In each study, methyl aminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37J/cm(2) ) delivered at high (75mW/cm(2) ) or low (15mW/cm(2) ) irradiance rates. Adjacent, unirradiated sites served as controls. Delayed type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. Results:??? High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression respectively; both p<0.0001); topical and oral nicotinamide reduced this immunosuppression by 59 and 66% respectively (both p<0.0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, NS), but caused 22% immunosuppression in the oral study (placebo arm; p=0.006); nicotinamide reduced this immunosuppression by 69% (p=0.045). Conclusions:??? While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Surjana, Devita %A Halliday, Gary M %A Martin, Andrew J %A Moloney, Fergal J %A Damian, Diona L %T Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. %B Journal of Investigative Dermatology %D 2012 %C United States %I Nature Publishing Group %V 132 %N 5 %P 1497-1500 %@ 1523-1747 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Halliday, Gary M %A Damian, Diona L %A Rana, Sabita %A Byrne, Scott N %T The suppressive effects of ultraviolet radiation on immunity in the skin and internal organs: Implications for autoimmunity. %B Journal of Dermatological Science %D 2012 %C Ireland %I Elsevier Ireland Ltd %V 66 %N 3 %P 176-182 %@ 1873-569X %X Low doses of sunlight that can be received during normal daily activities suppress immunity in humans. Both ultraviolet (UV) B (290-320nm) and UVA (320-400nm) are immunosuppressive. The wavelength dependence in humans shows distinct non-overlapping immunosuppressive peaks of solar effectiveness centred at 310nm UVB and 370nm UVA. In murine models of systemic immunosuppression low dose UV inhibits expansion of effector T cells in skin-draining lymph nodes, and retention of dermal effector memory CD8T cells at sites of antigen challenge. In addition to suppressing skin immunity, UV inhibits immunity in internal organs, including activation of CD8 T cells and cytotoxic T cell activity in the spleen, and memory T cell activation in the spleen and bone marrow. Neither of the chromophores responsible for UV suppression of skin immunity, DNA damage and urocanic acid, nor reactive oxygen species are involved in regulation of CD8 T cells in internal organs. Thus UVB impedes the activation and cytotoxicity of antigen-specific T cells in internal organs by mechanisms independent of suppression of skin immunity. These deleterious effects of low dose UV on skin immunity are likely to contribute to skin cancer, however UV suppression of immunity in internal organs may protect from autoimmunity. Epidemiological evidence suggests that sunlight protects from some autoimmune diseases directed towards internal organs. As UV suppression of skin and internal organ immunity appear to occur via different mechanisms, it may be possible to protect skin immunity and therefore reduce skin cancer incidence without preventing UV from reducing autoimmunity in internal organs. %Z FOR Codes: 110703 110799 %0 Journal Article %~ PubMed %A Damian, D L %A Matthews, Y J %A Phan, T A %A Halliday, G M %T An action spectrum for ultraviolet radiation-induced immunosuppression in humans. %B The British Journal of Dermatology %D 2011 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 164 %N 3 %P 657-659 %@ 1365-2133 %X The immune-suppressive effects of sunlight play a central role in skin carcinogenesis. Ultraviolet (UV) B radiation is highly immunosuppressive even at suberythemal doses, and longwave UVA is now also recognized to cause immunosuppression in humans. The relative contributions of UVA and UVB to immunosuppression by incidental daily sun exposure are, however, unclear. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Damian, Diona L %A Saw, Robyn P M %T Dramatic regression of cutaneous, nodal, and visceral melanoma metastases. %B Journal of the American Academy of Dermatology %D 2011 %C United States %I Mosby, Inc. %V 65 %N 3 %P 665-666 %@ 1097-6787 %X %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Surjana, Devita %A Damian, Diona L %T Nicotinamide in dermatology and photoprotection. %B Skinmed %D 2011 %C United States %I Le Jacq Communications, Inc. %V 9 %N 6 %P 360-365 %@ 1540-9740 %X Nicotinamide (the amide form of vitamin B3) has been used in dermatology for more than 40 years for a diverse range of conditions including acne, rosacea, autoimmune bullous dermatoses, and now the treatment and prevention of photoaging and photoimmunosuppression. The broad clinical effects of nicotinamide may be explained by its role as a cellular energy precursor, a modulator of inflammatory cytokines, and an inhibitor of the nuclear enzyme poly(adenosine diphosphate-ribose) polymerase-1, which plays a significant role in DNA repair, maintenance ofgenomic stability, and cellular response to injury including inflammation and apoptosis. This review outlines the use of nicotinamide for inflammatory dermatoses and photoaging and focuses on its emerging role in photoprotection. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Frost, Georgia A %A Halliday, Gary M %A Damian, Diona L %T Photodynamic therapy-induced immunosuppression in humans is prevented by reducing the rate of light delivery. %B The Journal of Investigative Dermatology %D 2011 %C United Kingdom, United States %I Nature Publishing Group %V 131 %N 4 %P 962-968 %@ 1523-1747 %X Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Damian, Diona L %A Thompson, John F %T Topical diphencyprone immunotherapy for a large primary melanoma on an elderly leg. %B American Journal of Clinical Dermatology %D 2011 %C New Zealand %I Adis International Ltd. %V 12 %N 6 %P 403-404 %@ 1175-0561 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Kurien, Anil M %A Damian, Diona L %A Moloney, Fergal J %T Trigeminal trophic syndrome treated with thermoplastic occlusion. %B Australasian Journal of Dermatology %D 2011 %C Australia %I Wiley-Blackwell Publishing Asia %V 52 %N 1 %P e1-e4 %@ 1440-0960 %X A 72-year-old man with a history of thrombotic CVA causing lateral medullary infarction presented with non-healing ulcers of the right side of the face of 5 months'' duration. After extensive investigations, a diagnosis of trigeminal trophic syndrome was made. The ulcers progressed relentlessly despite amitriptyline and gabapentin, and he was treated with a combination of carbamazepine and thermoplastic mask occlusion of the right side of his face. Over the next 10 weeks the shallower facial ulcers began to diminish in depth and diameter, and the deeper ulcers stopped progressing. Although the patient showed early signs of healing, he died because of complications from the CVA. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Halliday, Gary M %A Byrne, Scott N %A Damian, Diona L %T Ultraviolet a radiation: its role in immunosuppression and carcinogenesis. %B Seminars in Cutaneous Medicine and Surgery %D 2011 %C United States %I W.B. Saunders Co. %V 30 %N 4 %P 214-221 %@ 1558-0768 %X Ultraviolet A (UVA) radiation is immunosuppressive and mutagenic in humans and carcinogenic in animals. UVA suppresses immunity with a bell-shaped dose response. At doses equivalent to 15-20 minutes of sun exposure at noon, UVA contributes to approximately 75% of sunlight-induced immunosuppression. A recent action spectrum, indicating that 360-380 nm but not 320-350 nm UVA suppresses immunity in humans, suggests an important role for reactive oxygen species. UVA also causes an energy crisis in cells, and normalization of adenosine triphosphate with nicotinamide prevents UVA immunosuppression. UVA activation of the alternative complement pathway and defects in memory T-cell development are also involved. Human skin cancers contain mutations in the p53 and BRM genes that are consistent with being induced by UVA. UVA is also mutagenic in human skin equivalents. The basal layer of human skin is more susceptible to UVA-induced mutations than the upper layers. Because skin cancers arise from these basal proliferating cells, this finding is likely to be important and could be attributable to low levels of the DNA repair enzyme OGG1 in basal cells. UVA is therefore likely to make a larger contribution to UVA-induced skin carcinogenesis in humans than is predicted by small animal models as the result of being immunosuppressive and mutagenic for basal keratinocytes. %Z FOR Codes: 111299 110709 110304 %0 Journal Article %~ PubMed %A Matthews, Yasmin J %A Halliday, Gary M %A Phan, Tai A %A Damian, Diona L %T A UVB Wavelength Dependency for Local Suppression of Recall Immunity in Humans Demonstrates a Peak at 300 nm. %B The Journal of investigative dermatology %D 2010 %C United Kingdom, United States %I Nature Publishing Group %V 130 %N 6 %P 1680-4 %@ 1523-1747 %X UVB radiation is a potent environmental carcinogen that not only causes mutations in the skin but also profoundly suppresses skin immune responses. Although this UVB-induced suppression of antitumor immunity has a key role in skin cancer development, the wavelengths within UVB causing greatest in vivo immunosuppression in humans are as yet unknown. We have identified a wavelength dependency for immunosuppression in humans across the UVB spectrum. We established linear dose-response curves for UV-induced local suppression of recall contact hypersensitivity responses at four wavelengths between 289 and 322 nm and found peak immune suppressive effectiveness at 300 nm and no detectable suppression at 322 nm within a physiologically relevant dose range. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Damian, Diona L %A Bertouch, Jim V %T A plethora of protein. %B The American Journal of Medicine %D 2010 %C United States %I Excerpta Medica, Inc. %V 123 %N 10 %P 904-906 %@ 1555-7162 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Park, Joohong %A Halliday, Gary M %A Surjana, Devita %A Damian, Diona L %T Nicotinamide Prevents Ultraviolet Radiation-induced Cellular Energy Loss. %B Photochemistry and photobiology %D 2010 %C United States %I Wiley-Blackwell Publishing, Inc. %V 86 %N 4 %P 942-8 %@ 1751-1097 %X UV radiation is carcinogenic by causing mutations in the skin and also by suppressing cutaneous antitumor immunity. We previously found nicotinamide (vitamin B3) to be highly effective at reducing UV-induced immunosuppression in human volunteers, with microarray studies on in vivo irradiated human skin suggesting that nicotinamide normalizes subsets of apoptosis, immune function and energy metabolism-related genes that are downregulated by UV exposure. Using human adult low calcium temperature keratinocytes, we further investigated nicotinamide''s effects on cellular energy metabolism. We found that nicotinamide prevented UV-induced cellular ATP loss and protected against UV-induced glycolytic blockade. To determine whether nicotinamide alters the effects of UV-induced oxidative stress posttranslationally, we also measured UV-induced reactive oxygen species (ROS). Nicotinamide had no effect on ROS formation, and at the low UV doses used in these studies, equivalent to ambient daily sun exposure, there was no evidence of apoptosis. Hence, nicotinamide appears to exert its UV protective effects on the skin via its role in cellular energy pathways. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Damian, Diona L %T Photoprotective effects of nicotinamide. %B Photochemical & Photobiological Sciences %D 2010 %C United Kingdom, Swit %I Royal Society of Chemistry %V 9 %N 4 %P 578-585 %@ 1474-9092 %X Sun protective measures can reduce numbers of both precancerous actinic keratoses and cutaneous squamous cell carcinomas within relatively short periods of time even in high-risk populations. Sunscreens, which tend to provide greater protection against shortwave UVB than against longer wavelength UVA radiation, can however provide only partial protection from the mutagenic and immune suppressive effects of sunlight. In large part, this reflects poor compliance with proper sunscreen application and reapplication. Skin cancer is by far the most common malignancy in Caucasian populations, and additional strategies to reduce the morbidity and economic burden of this disease are now urgently needed. Nicotinamide, the amide form of vitamin B3, is an inexpensive agent which is used for a variety of dermatological applications with little or no toxicity even at high doses. Nicotinamide has photoprotective effects against carcinogenesis and immune suppression in mice, and is photoimmunoprotective in humans when used as a lotion or orally. UV irradiation depletes keratinocytes of cellular energy and nicotinamide, which is a precursor of nicotinamide adenine dinucleotide, may act at least in part by providing energy repletion to irradiated cells. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Moloney, F %A Vestergaard, M %A Radojkovic, B %A Damian, D %T Randomized, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses. %B The British journal of dermatology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 162 %N 5 %P 1138-9 %@ 1365-2133 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Christou, Elizabeth M %A Damian, Diona L %A Thompson, John F %T Regressing metastatic melanoma and vitiligo-like depigmentation in an Indigenous Australian. %B The Medical Journal of Australia %D 2010 %C Australia %I Australasian Medical Publishing Company Pty. Ltd. %V 192 %N 3 %P 171 %@ 0025-729X %X %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Surjana, Devita %A Halliday, Gary M %A Damian, Diona L %T Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. %B Journal of Nucleic Acids %D 2010 %C United States %I Sage - Hindawi Access to Research %V 2010 %N %P 157591 %@ 2090-021X %X Nicotinamide is a water-soluble amide form of niacin (nicotinic acid or vitamin B3). Both niacin and nicotinamide are widely available in plant and animal foods, and niacin can also be endogenously synthesized in the liver from dietary tryptophan. Nicotinamide is also commercially available in vitamin supplements and in a range of cosmetic, hair, and skin preparations. Nicotinamide is the primary precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in ATP production and the sole substrate of the nuclear enzyme poly-ADP-ribose polymerase-1 (PARP-1). Numerous in vitro and in vivo studies have clearly shown that PARP-1 and NAD(+) status influence cellular responses to genotoxicity which can lead to mutagenesis and cancer formation. This paper will examine the role of nicotinamide in the protection from carcinogenesis, DNA repair, and maintenance of genomic stability. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Martiniuk, Frank %A Damian, Diona L %A Thompson, John F %A Scolyer, Richard A %A Tchou-Wong, Kam-Meng %A Levis, William R %T TH17 is involved in the remarkable regression of metastatic malignant melanoma to topical diphencyprone. %B Journal of Drugs in Dermatology %D 2010 %C United States %I Journal of Drugs in Dermatology, Inc. %V 9 %N 11 %P 1368-1372 %@ 1545-9616 %X The authors provide an update on a previously reported patient with in-transit metastatic melanoma of the scalp treated with topical diphencyprone (DPCP). Molecular studies implicate the thymus-derived TH17 lymphocyte subset in a remarkable immunotherapeutic regression. The authors performed RT-PCR of total RNA from paraffin-embedded tissue before and after treatment with DPCP. Before treatment with DPCP, the authors found elevated expression of IL 17C/D/E/F; after treatment there was no detectable expression. Conversely, increased expression of PLZF/CD27 and CTLA4 was seen after treatment with no expression before treatment. No expression of IL17A/B, CD7, RORgTand FoxP3 were before or after treatment. Conclusions are limited to only the time samples were obtained. Remarkable regression of an in-transit metastatic melanoma treated with the immunomodulatory agent DPCP showed gain and loss of gene expression of the TH17 pathway. Further study of this pathway from NK to NK-T to TH7 and TH1 cells both with and without accessory or dendritic cells will improve understanding of contact sensitizers as topical immunomodulators. %Z FOR Codes: 111204 %0 Journal Article %~ PubMed %A Damian, Diona L %A Kim, Young Jin %A Dixon, Katie M %A Halliday, Gary M %A Javeri, Arash %A Mason, Rebecca S %T Topical calcitriol protects from UV-induced genetic damage but suppresses cutaneous immunity in humans. %B Experimental dermatology %D 2010 %C United Kingdom, Unit %I Wiley-Blackwell Publishing Ltd. %V 19 %N 8 %P e23-30 %@ 1600-0625 %X Calcitriol, the biologically active form of vitamin D, has been reported to cause both suppressive and protective immune effects in mice. Its immune effects in vivo in humans are unclear. We investigated the in vivo effects of topical calcitriol on minimal erythema dose and skin immune responses in healthy volunteers. We found that calcitriol did not protect from ultraviolet (UV)-induced erythema (sunburn) when applied either 24 h before or immediately after irradiation, although it decreased the density of sunburn cells and thymine dimers seen on biopsy when applied 24 h before and again immediately after irradiation. Using the Mantoux reaction as a model of skin immunity, we found that topical calcitriol applied at high total doses reduced the Mantoux responses of nearby untreated, unirradiated skin, suggesting a para-local or systemic immunosuppressive effect not observed with lower calcitriol doses. We then measured UV-induced suppression of Mantoux reactions at vehicle-treated sites and sites treated with low-dose calcitriol, and found that calcitriol neither reduced nor enhanced UV-induced immunosuppression. Despite calcitriol reducing UV-induced DNA damage, which should protect the immune system, it has immunosuppressive effects in our model which may help to explain the efficacy of analogues such as calcipotriol in the treatment of psoriasis. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Matthews, Y J %A Damian, D L %T Topical photodynamic therapy is immunosuppressive in humans. %B The British journal of dermatology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 162 %N 3 %P 637-41 %@ 1365-2133 %X Visible light irradiation after application of a photosensitizer (topical photodynamic therapy; PDT) is increasingly used to treat nonmelanoma skin cancers and premalignant actinic keratoses. PDT can provide a cosmetically superior alternative to surgery, but carries failure rates of 10-40%. While some murine studies have suggested immune enhancement by PDT, others reported immunosuppressive effects, which may indicate impaired antitumour immunity and thus compromised tumour clearance. %Z FOR Codes: 111204 %0 Journal Article %~ PubMed %A Damian, Diona L %A Matthews, Yasmin J %A Halliday, Gary M %T Topical riboflavin attenuates ultraviolet B- and ultraviolet A-induced immunosuppression in humans. %B Photodermatology, Photoimmunology & Photomedicine %D 2010 %C United States, Unit %I Wiley-Blackwell Publishing, Inc %V 26 %N 2 %P 66-69 %@ 1600-0781 %X BACKGROUND: Riboflavin (vitamin B(2)) plays a key role in cellular energy metabolism. We have observed previously that nicotinamide (vitamin B(3)), which is also centrally involved in cellular energy restoration after UV irradiation, is highly immune protective in humans. We thus hypothesized that riboflavin might also confer immune protection. METHODS: We irradiated healthy, nickel-allergic volunteers with narrowband UVA (385 nm) and UVB (300 nm) at separate sites on the lower back. These areas were treated with riboflavin solution or vehicle at 24 h and again at 30 min before UV exposure. Forty-eight hours after irradiation, volunteers were patch tested with nickel-containing Finn chambers, at both irradiated and nonirradiated sites, with and without prior riboflavin treatment. The resulting contact hypersensitivity reactions at each site were then measured 72 h later with a reflectance erythema meter in order to determine and compare the immune suppressive effects of each intervention. RESULTS: We observed that low doses of both UVB and longwave UVA1 were immune suppressive in humans. Topical riboflavin conferred immune protection against both wavebands. CONCLUSIONS: Riboflavin is immune protective in humans, and this may reflect the role of the B group vitamins in cellular energy restoration after UV exposure. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Matthews, Yasmin J %A Halliday, Gary M %A Phan, Tai A %A Damian, Diona L %T Wavelength dependency for UVA-induced suppression of recall immunity in humans. %B Journal of dermatological science %D 2010 %C Ireland, Japan %I Elsevier Ireland Ltd %V 59 %N 3 %P 192-7 %@ 1873-569X %X Ultraviolet (UV) A radiation, which has both mutagenic and immune suppressive effects on the skin, is increasingly recognised as a key contributor to cutaneous carcinogenesis. Whilst short wavelength UVB (290-320 nm) is well-recognised as an environmental health hazard, the dangers of UVA (320-400 nm) are relatively unexplored. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Yiasemides, Eleni %A Sivapirabu, Geetha %A Halliday, Gary M %A Park, Joohong %A Damian, Diona L %T Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. %B Carcinogenesis %D 2009 %C United Kingdom %I Oxford University Press %V 30 %N 1 %P 101-5 %@ 1460-2180 %X Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight. %Z FOR Codes: 1112 %0 Journal Article %~ PubMed %A Damian, Diona L %A Shannon, Kerwin F %A Saw, Robyn P %A Thompson, John F %T Topical diphencyprone immunotherapy for cutaneous metastatic melanoma. %B Australasian Journal of Dermatology %D 2009 %C Australia %I Wiley-Blackwell Publishing Asia %V 50 %N 4 %P 266-271 %@ 1440-0960 %X Topical immunotherapy with contact sensitizers for metastatic melanoma was first reported more than 30 years ago. Diphencyprone (DPCP) immunotherapy is frequently used to treat cutaneous warts and alopecia areata, and we have previously reported the use of DPCP as a single agent to successfully treat extensive, radiotherapy-resistant melanoma metastases on the scalp. We now report DPCP treatment of a further six patients with cutaneous metastatic melanoma. Of seven patients treated with DPCP thus far, four have demonstrated complete responses of their cutaneous lesions and three have had partial responses. The treatment was well-tolerated by all patients. Topical immunotherapy with DPCP is inexpensive and relatively non-invasive and should be considered in patients with locally advanced skin metastases that are unsuitable for other therapies. %Z FOR Codes: 111204 %0 Journal Article %~ PubMed %A Sivapirabu, G %A Yiasemides, E %A Halliday, G M %A Park, J %A Damian, D L %T Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. %B The British journal of dermatology %D 2009 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 161 %N 6 %P 1357-64 %@ 1365-2133 %X Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A de Zwaan, Sally E %A Iland, Harry J %A Damian, Diona L %T Treatment of refractory pyoderma gangrenosum with intravenous immunoglobulin. %B The Australasian Journal of Dermatology %D 2009 %C Australia %I Blackwell Publishing Asia %V 50 %N 1 %P 56-59 %@ 0004-8380 %X We report a patient with pyoderma gangrenosum successfully treated with intravenous immunoglobulin. He had previously been treated for 4 years with high-dose corticosteroids and had developed insulin-dependent diabetes mellitus. Multiple corticosteroid-sparing agents had failed or were contraindicated. He developed no adverse effects from intravenous immunoglobulin, which allowed reduction of his prednisone to 3 mg/day, and his ulcer has completely healed. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Damian, Diona L %A Yiasemides, Eleni %A Gupta, Sandeep %A Armour, Katherine %T Ultrasound therapy for lipodermatosclerosis. %B Archives of dermatology %D 2009 %C United States %I American Medical Association %V 145 %N 3 %P 330-2 %@ 1538-3652 %X %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A McCombie, Anna-Marie %A Mason, Rebecca S %A Damian, Diona L %T Vitamin D deficiency in Sydney skin cancer patients. %B The Medical Journal of Australia %D 2009 %C Australia %I Australasian Medical Publishing Company Pty. Ltd %V 190 %N 2 %P 102 %@ 1326-5377 %X %Z FOR Codes: 111104 %0 Journal Article %~ PubMed %A Wiener, M %A Damian, D L %A Thompson, J F %T Systemic phototoxicity following intralesional rose bengal for subcutaneous melanoma metastases. %B Dermatology %D 2008 %C Switzerland %I S. Karger AG %V 216 %N 4 %P 361-362 %@ 1421-9832 %X %Z FOR Codes: 110304 1112 %0 Journal Article %~ Isi %A Halliday, G %A Phan, T %A Renwick, Y %A Damian, D %T Comparison of the immune suppressive effectiveness of UVB and long-wave UVA in humans %B JOURNAL OF INVESTIGATIVE DERMATOLOGY %D 2007 %C United Kingdom %I Elsevier Ireland Ltd %V 127 %N %P 2690-2690 %@ 0022-202X %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Halpagi, P %A Grigg, J %A Klistorner, A %A Damian, D L %T Night blindness following low-dose isotretinoin. %B Journal of the European Academy of Dermatology and Venereology : JEADV %D 2007 %C United Kingdom %I Blackwell Publishing Ltd. %V 22 %N 0 %P 893-4 %@ 0926-9959 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Damian, Diona L %A Thompson, John F %T Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. %B Journal of the American Academy of Dermatology %D 2007 %C United States %I Mosby, Inc. %V 56 %N 5 %P 869-871 %@ 1097-6787 %X Diphencyprone is a potent contact sensitizer sometimes used to treat alopecia areata and cutaneous warts. A patient with previous primary nodular melanoma on the scalp developed extensive, confluent cutaneous metastases near the primary site, unsuitable for treatment with surgery or radiotherapy. Topical treatment with diphencyprone as a single agent resulted in regression of all lesions, and the patient remains well 18 months later. Topical immunotherapy with diphencyprone was an inexpensive and well-tolerated treatment for extensive cutaneous melanoma metastases in our patient unsuitable for other therapies. %Z FOR Codes: %0 Journal Article %~ PubMed %A Damian, Diona L %A Patterson, Clare R S %A Stapelberg, Michael %A Park, Joohong %A Barnetson, Ross St C %A Halliday, Gary M %T UV Radiation-Induced Immunosuppression Is Greater in Men and Prevented by Topical Nicotinamide. %B The Journal of investigative dermatology %D 2007 %C United States %I Blackwell Publishing, Inc. %V 128 %N 2 %P 447-54 %@ 0022-202X %X UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub %Z FOR Codes: %0 Journal Article %~ PubMed %A Howes, Renae A %A Halliday, Gary M %A Damian, Diona L %T Effect of topical melatonin on ultraviolet radiation-induced suppression of Mantoux reactions in humans. %B Photodermatology, photoimmunology & photomedicine %D 2006 %C Denmark %I Blackwell Munksgaard %V 22 %N 5 %P 267-9 %@ 0905-4383 %X Background: Melatonin, the central neurohormone in circadian rhythm pathways, is recognized to have a variety of immune-enhancing effects. It has previously been shown to reduce ultraviolet (UV) radiation-induced erythema in mice and in humans, but there are as yet no published studies on the effects of melatonin on UV-induced immunosuppression in humans. Methods: We investigated the effects of topical melatonin on solar-simulated (ss) UV-induced suppression of Mantoux reactions in 16 healthy, Mantoux-positive volunteers. Melatonin (5%) and its vehicle were applied in a double-blinded manner to separate areas on the lower back, immediately after each of three consecutive daily ssUV exposures. Various sites on the back received either no irradiation or one of three-graded ssUV doses. Mantoux testing was performed at each site 24 h after the final irradiation, and assessed 72 h later using a reflectance erythema meter. In a separate group of 19 volunteers, the effect of melatonin on minimal erythema dose was assessed both visually and with an erythema meter. Results: We found dose-responsive UV-induced suppression of the Mantoux response in the presence of both vehicle and melatonin; melatonin did not prevent UV-induced immunosuppression in this model. Melatonin was also found to have no effect on the minimal erythema dose. Conclusions: Melatonin conferred no protection against immune suppression or sunburn when applied topically to human skin immediately after irradiation. %Z FOR Codes: 110304 %0 Journal Article %~ PubMed %A Herat, Asoka %A Shirato, Kyoko %A Damian, Diona L %A Finlayson, Robert %A Whitfeld, Margot %T Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease in a HIV-positive individual. %B The Australasian journal of dermatology %D 2006 %C Australia %I Blackwell Publishing Asia %V 47 %N 2 %P 120-3 %@ 0004-8380 %X A 54-year-old HIV-positive homosexual man presented with erythematous and pigmented plaques on background erythema in the perianal region, histologically consistent with Bowen''s disease. Perianal Bowen''s disease represents high-grade anal intraepithelial neoplasia, which is considered a precursor lesion of invasive anal squamous cell carcinoma. This patient''s anal intraepithelial neoplasia was unresponsive to multiple treatment modalities including cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy. He progressed to develop a poorly differentiated squamous cell carcinoma of the anus three and a half years after the Bowen''s disease was diagnosed. The squamous cell carcinoma was treated with combined chemoradiation. A recurrence of high-grade anal intraepithelial neoplasia was noted 6 months after completion of chemoradiation. %Z FOR Codes: %0 Journal Article %~ PubMed %A Phan, Tai A %A Halliday, Gary M %A Barnetson, Ross Stc %A Damian, Diona L %T Melanin differentially protects from the initiation and progression of threshold UV-induced erythema depending on UV waveband. %B Photodermatology, photoimmunology & photomedicine %D 2006 %C Denmark %I Blackwell Munksgaard %V 22 %N 4 %P 174-80 %@ 0905-4383 %X This study aimed to determine the relationship between various measures of constitutive skin pigmentation and erythema caused by solar-simulated UV (ssUV), 290 and 310 nm UV. Skin pigmentation was assessed clinically by skin typing as well as objectively by measurement of the melanin index (MI) by reflectance spectroscopy. Subjects having Fitzpatrick skin types I-IV were exposed to graded doses of ssUV and either narrowband 310 nm (n=70) or 290 nm (n=69) UV, and assessed 24 h after exposure. Minimal erythema dose (MED) was assessed visually as the lowest dose that caused minimally perceptible erythema. Susceptibility to further development of erythema with higher exposure doses was measured by the gradient of erythema dose-response curves. This was determined by linear regression using reflectance spectrometry data beyond the MED. Although there was considerable variation within each skin type, MI and ssUV MED increased with increasing Fitzpatrick skin type. MI correlated with ssUV MED and 310 nm UV MED, but not 290 nm UV MED. There was also a significant negative correlation between MI and erythema dose-response gradients caused by ssUV, 310 and 290 nm UV. Melanin situated near the basal epidermis may not protect from the initial development of threshold erythema caused by 290 nm UV because it penetrates poorly past the stratum corneum and is not well absorbed by melanin in vivo compared with 310 nm UV. Higher erythemal 290 nm UV doses may reach basal epidermal melanin, which may then afford protection against further 290 nm UV erythema. %Z FOR Codes: %0 Journal Article %~ PubMed %A Phan, Tai A %A Halliday, Gary M %A Barnetson, Ross StC %A Damian, Diona L %T Spectral and dose dependence of ultraviolet radiation-induced immunosuppression. %B Frontiers in bioscience : a journal and virtual library %D 2006 %C United States %I Frontiers in Bioscience %V 11 %N %P 394-411 %@ 1093-4715 %X Ultraviolet radiation (UV) wavelength and dose dependence has been demonstrated for a number of cutaneous endpoints such as erythema, pigment darkening, DNA damage, and photocarcinogenesis. More recently, a number of in-vitro and in-vivo models of UV immunosuppression have implicated UVA (320-400 nm) in immune protection as well as immune suppression. While the wavelength dependencies for immunosuppression within UVB have been well established in mice, the exact role of specific UVA wavelengths has been less clear. Moreover, in humans, the spectral dependence of UV immunosuppression is even less well established. This review firstly outlines the established UV action spectra for a variety of cutaneous effects. The waveband and dose dependence of UV immunosuppression and its mechanisms are explored with a focus on in-vivo models. Finally, since UV immunosuppression along with DNA damage is thought to play a central role in the development of skin cancer, a clearer understanding of the immunosuppressive potential of discrete UV wavebands will allow a more rational approach to our understanding and prevention of skin cancer. %Z FOR Codes: %0 Journal Article %~ PubMed %A Howes, Renae A %A Halliday, Gary M %A Barnetson, Ross Stc %A Friedmann, Adam C %A Damian, Diona L %T Topical capsaicin reduces ultraviolet radiation-induced suppression of Mantoux reactions in humans. %B Journal of Dermatological Science %D 2006 %C Ireland %I Elsevier Ireland Ltd %V 44 %N 2 %P 113-115 %@ 0923-1811 %X %Z FOR Codes: 110304 %0 Journal Article %A Damian, Diona %A Barnetson, Ross %A Thompson, John %T Treatment of refractory chromomycosis by isolated limb infusion with melphalan and actinomycin D %B Journal of Cutaneous Medicine and Surgery %D 2006 %C Canada %I BC Decker Inc. %V 10 %N 1 %P 48-51 %@ 1203-4754 %X %Z FOR Codes: