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Atopic dermatitis and thermal therapy: Evaluation in children under 15
P2314 Atopic dermatitis and thermal therapy: Evaluation in children under 15 Charles Taieb, MD, MBA, Pierre Fabre, Boulogne cedex, France; Marie Ange Martinsic, PhD, Eau Thermale Avene, Boulogne cedex, France; Therese Nocera, MD, Eau Thermale Avene, Lavaur, France; Sami Boussetta, PhD, Pierre Fabre, Boulogne, France Introduction: Skin diseases have a strong impact on the physical and mental wellbeing of patients. The large number of studies on quality of life (qol) is confirmation of this. It is clear that dermatological diseases do not only affect the life of the child but also the life of his/her parents and possibly the whole family. Objective: The Ave`ne hydrotherapy center (HC), which every year receives around 2500 patients, cares for a growing number of children under 15 every year, around 30% in 2006. Usually one of the parents accompanies the child. Given the importance of the notions of quality of life in the requirements for treating children, it seemed appropriate to conduct an evaluation of the qol of the children treated at the Ave`ne HC and that of their parents. Methods During the 2005 and 2006 seasons, the qol of the children was evaluated using the cartoon version of the CDLQI (Children’s Dermatology Life Quality Index). To evaluate the qol of the parents, a generic scale (SF-12) was used. The questionnaires (Q) were filled in by one of the 2 parents: when the child arrived at the Ave`ne HC (consultation on arrival), at the end of the thermal therapy (TT; week 3) but also at 3 and 6 months (after the child had gone home). Results: The average age was respectively 10.1 6 3.2 years for the children suffering from AD (n ¼ 201). In order to evaluate the change in qol following the TT and away from the therapy, we isolated the subjects who completed the 4 Q. For the atopic children, the CDLQI score on arrival was 23.569.8; following therapy it was 17.9 6 16.2. The evaluations at 3 and 6 months gave respective CDLQI scores of 14.9 6 15.1 and 16.5 6 14.8. The change in the score was compared to the score obtained on arrival, and there was a significant improvement in qol at 3 weeks. Conclusion: This study shows an alteration in the qol of parents whose children suffer from chronic dermatosis. The overall treatment at the HC improves qol—in its mental dimension—of the parents. The results for the CDLQI are higher than the average scores obtained during the study done with nurses evaluating the qol of children suffering from AD in England (20%) but lower than the average score obtained at the audit of AD done by the British Association of Dermatologists (35%). Our study confirms the pertinence of using TT, but also for the first time demonstrates sustained improvement in qol at 3 months (P ¼.004) and perpetuation at 6 (P ¼ .035) for children under 15. 50% supported by Eau Thermale Avene and 50% by Pierre Fabre´.
PHOTOBIOLOGY, PHOTOTHERAPY, AND PHOTOSENSITIVITY DISEASES P2400 The 8-oxo-guanine repair enzyme OGG1 encapsulated in liposomes reduces MMP-1 secretion and increases collagen production by dermal fibroblasts in a paracrine system Kelly Dong, MS, AGI Dermatics, Freeport, NY, United States; Niusha Damaghi, AGI Dermatics, Freeport, NY, United States; Kenneth Smiles, PhD, AGI Dermatics, Freeport, NY, United States; Daniel Yarosh, PhD, AGI Dermaitcs, Freeport, NY, United States 8-oxo-guanine (8-oxo-G) is a DNA lesion induced by reactive oxygen species (ROS) generated by UVA irradiation and other environmental stressors, or in the course of normal cellular metabolism. Concomitantly or consequently, ROS also stimulate the production and/or secretion of matrix metalloproteinase-1 (MMP-1) in dermal fibroblasts (NHDF) and of tumor necrosis factor-a (TNF-a) in epidermal keratinocytes (NHEK). Both MMP-1 and TNF-a are factors implicated in the photoaging of the skin. 8-oxo-G lesions are primarily repaired by a natural base excision repair pathway using the enzyme 8-oxoguanine DNA glycosylase-1 (OGG1). We have shown that delivery of liposome- encapsulated OGG1 into NHDF increases the rate of repair of solar-simulating (ss) UV-induced 8-oxo-G lesions, reduces mitochondrial toxicity and MMP-1 secretion, and prevents collagen loss without affecting TNF-a secretion. Conversely, the repair of 8-oxo-G lesions in NHEK by liposome-encapsulated OGG1 is accompanied by a reduction in ssUV-induced TNF-a secretion. Collectively, these results indicate that (1) a portion of the biochemical changes observed in response to ssUV irradiation of the skin cells are directly related to the oxidative damage inflicted upon their DNA, and (2) the OGG1-loaded liposomes are capable of counteracting the ssUV damage in keratinocytes and fibroblasts. The data also suggest that the detrimental effects of ssUV radiation on the epidermis may be propagated into the underlying dermis through soluble factors released by the directly hit keratinocytes. If so, repair of ssUV-induced DNA damage by OGG1 in the epidermal keratinocytes may also prevent the by-stander effect in the fibroblasts by reducing, for instance, the release of TNF-a from NHEK. Accordingly, we observed that growing NHDF for 48 hours in medium harvested from ssUV-irradiated NHEK induced more MMP-1 secretion and greater collagen loss compared to direct irradiation of NHDF with the same ssUV dose. We also used this model system to investigate whether OGG1 liposomes would be effective in diminishing the bystander effect elicited by ssUV through the release of soluble factors. Treatment of ssUV-irradiated NHEK with OGG1 liposomes for 24 hours suppressed the induction of MMP-1 secretion by NHDF receiving the medium from the irradiated keratinocytes in a dose-dependent manner. In these fibroblasts the reduction in MMP1 secretion was accompanied by diminished collagen loss. For both end-points the effect of the paracrine signaling by transferred medium exceeded the direct effect of corresponding amounts of OGG1 liposomes on irradiated NHDF. Comparison between mRNA transcription and protein secretion of MMP-1 and collagen 1A1 indicates that OGG1 liposome treatment reduces MMP-1 and increases collagen levels in the directly hit and in the by-stander cells through post-transcriptional events. Commercial support: None identified.
P2402
We will present a case report of an infant with an unusual cutaneous manifestation associated with TPN dependent malabsorption, with a unique chomosomal abnormality and facial dysmorphology. More details will follow, including better delineation of the gut abnormality, but the work-up is in progress and it does not appear at this time that the malabsorption is related to the histiocytosis.
Repair of 7,8-dihydro-8-oxoguanine reduces caspase-9erelated apoptosis in normal human epidermal keratinocytes Nelli Markova, PhD, Freeport, NY, United States; Stephanie Nay, AGI Dermatics, Freeport, NY, United States; Kenneth Smiles, PhD, AGI Dermatics, Freeport, NY, United States; Daniel Yarosh, PhD, AGI Dermatics, Freeport, NY, United States Solar ultraviolet exposure induces many adverse short- and long-term effects in skin, including inflammation, photoaging, and skin cancer. The cellular processes leading to UV-induced skin damage involve direct interaction of keratinocyte DNA with UV radiation, DNA, and protein lesions caused by UV-induced reactive oxygen species, and the perturbation of apoptotic responses aimed at preserving the cells in which the damage can be faithfully repaired and eliminating those that have been irreversibly compromised. The development of effective skin protection against photoaging and skin cancer requires detailed understanding of the underlying molecular mechanisms, since both the nature and the magnitude of the cellular responses vary with the quality and quantity of UV exposure. Herein, we present evidence that irradiation of sub-confluent epidermal keratinocytes with solar simulating UV (ssUV) induces the intrinsic apoptotic pathway, as determined by an 8-fold activation of the initiator caspase-9 in a dose-dependent manner. This activation can be completely suppressed by pre- and/or postirradiation treatment of the keratinocytes with liposomes encapsulating the DNA glycosylase enzyme OGG1. OGG1 is a component of the base excision repair system (BER), which localizes both in the nucleus and in the mitochondria and repairs the signature oxidative DNA lesion 7,8-dihydro-8-oxoguanine (8-oxo-G). In NHEK at 90% to 95% confluence, which resemble more the differentiated suprabasal keratinocytes within the epidermis, ssUV induced less than 2-fold caspase 9 activation that was unaffected by OGG1 presence. These results indicate that increasing OGG1 content within proliferating NHEK not only repairs the nuclear and mitochondrial oxidative DNA damage and thus prevents the accumulation of 8-oxo-G with UV exposure but also preserves the basal keratinocytes from ssUV-induced cell death and allows more time for DNA repair. In the differentiating keratinocytes destined to be shed off, suppression of caspase-9 activation may be inconsequential and therefore not part of the cellular defense mechanism.
Commercial support: None identified.
Commercial support: None identified.
P2315 Unusual manifestation of noneLangerhans cell histiocytosis an infant with a malabsorption syndrome David Adelson, MD, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Miranda Smith, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
AB110
J AM ACAD DERMATOL
FEBRUARY 2008
PHOTOBIOLOGY, PHOTOTHERAPY, AND PHOTOSENSITIVITY DISEASES P2400 The 8-oxo-guanine repair enzyme OGG1 encapsulated in liposomes reduces MMP-1 secretion and increases collagen production by dermal fibroblasts in a paracrine system Kelly Dong, MS, AGI Dermatics, Freeport, NY, United States; Niusha Damaghi, AGI Dermatics, Freeport, NY, United States; Kenneth Smiles, PhD, AGI Dermatics, Freeport, NY, United States; Daniel Yarosh, PhD, AGI Dermaitcs, Freeport, NY, United States 8-oxo-guanine (8-oxo-G) is a DNA lesion induced by reactive oxygen species (ROS) generated by UVA irradiation and other environmental stressors, or in the course of normal cellular metabolism. Concomitantly or consequently, ROS also stimulate the production and/or secretion of matrix metalloproteinase-1 (MMP-1) in dermal fibroblasts (NHDF) and of tumor necrosis factor-a (TNF-a) in epidermal keratinocytes (NHEK). Both MMP-1 and TNF-a are factors implicated in the photoaging of the skin. 8-oxo-G lesions are primarily repaired by a natural base excision repair pathway using the enzyme 8-oxoguanine DNA glycosylase-1 (OGG1). We have shown that delivery of liposome- encapsulated OGG1 into NHDF increases the rate of repair of solar-simulating (ss) UV-induced 8-oxo-G lesions, reduces mitochondrial toxicity and MMP-1 secretion, and prevents collagen loss without affecting TNF-a secretion. Conversely, the repair of 8-oxo-G lesions in NHEK by liposome-encapsulated OGG1 is accompanied by a reduction in ssUV-induced TNF-a secretion. Collectively, these results indicate that (1) a portion of the biochemical changes observed in response to ssUV irradiation of the skin cells are directly related to the oxidative damage inflicted upon their DNA, and (2) the OGG1-loaded liposomes are capable of counteracting the ssUV damage in keratinocytes and fibroblasts. The data also suggest that the detrimental effects of ssUV radiation on the epidermis may be propagated into the underlying dermis through soluble factors released by the directly hit keratinocytes. If so, repair of ssUV-induced DNA damage by OGG1 in the epidermal keratinocytes may also prevent the by-stander effect in the fibroblasts by reducing, for instance, the release of TNF-a from NHEK. Accordingly, we observed that growing NHDF for 48 hours in medium harvested from ssUV-irradiated NHEK induced more MMP-1 secretion and greater collagen loss compared to direct irradiation of NHDF with the same ssUV dose. We also used this model system to investigate whether OGG1 liposomes would be effective in diminishing the bystander effect elicited by ssUV through the release of soluble factors. Treatment of ssUV-irradiated NHEK with OGG1 liposomes for 24 hours suppressed the induction of MMP-1 secretion by NHDF receiving the medium from the irradiated keratinocytes in a dose-dependent manner. In these fibroblasts the reduction in MMP1 secretion was accompanied by diminished collagen loss. For both end-points the effect of the paracrine signaling by transferred medium exceeded the direct effect of corresponding amounts of OGG1 liposomes on irradiated NHDF. Comparison between mRNA transcription and protein secretion of MMP-1 and collagen 1A1 indicates that OGG1 liposome treatment reduces MMP-1 and increases collagen levels in the directly hit and in the by-stander cells through post-transcriptional events. Commercial support: None identified.
P2402
We will present a case report of an infant with an unusual cutaneous manifestation associated with TPN dependent malabsorption, with a unique chomosomal abnormality and facial dysmorphology. More details will follow, including better delineation of the gut abnormality, but the work-up is in progress and it does not appear at this time that the malabsorption is related to the histiocytosis.
Repair of 7,8-dihydro-8-oxoguanine reduces caspase-9erelated apoptosis in normal human epidermal keratinocytes Nelli Markova, PhD, Freeport, NY, United States; Stephanie Nay, AGI Dermatics, Freeport, NY, United States; Kenneth Smiles, PhD, AGI Dermatics, Freeport, NY, United States; Daniel Yarosh, PhD, AGI Dermatics, Freeport, NY, United States Solar ultraviolet exposure induces many adverse short- and long-term effects in skin, including inflammation, photoaging, and skin cancer. The cellular processes leading to UV-induced skin damage involve direct interaction of keratinocyte DNA with UV radiation, DNA, and protein lesions caused by UV-induced reactive oxygen species, and the perturbation of apoptotic responses aimed at preserving the cells in which the damage can be faithfully repaired and eliminating those that have been irreversibly compromised. The development of effective skin protection against photoaging and skin cancer requires detailed understanding of the underlying molecular mechanisms, since both the nature and the magnitude of the cellular responses vary with the quality and quantity of UV exposure. Herein, we present evidence that irradiation of sub-confluent epidermal keratinocytes with solar simulating UV (ssUV) induces the intrinsic apoptotic pathway, as determined by an 8-fold activation of the initiator caspase-9 in a dose-dependent manner. This activation can be completely suppressed by pre- and/or postirradiation treatment of the keratinocytes with liposomes encapsulating the DNA glycosylase enzyme OGG1. OGG1 is a component of the base excision repair system (BER), which localizes both in the nucleus and in the mitochondria and repairs the signature oxidative DNA lesion 7,8-dihydro-8-oxoguanine (8-oxo-G). In NHEK at 90% to 95% confluence, which resemble more the differentiated suprabasal keratinocytes within the epidermis, ssUV induced less than 2-fold caspase 9 activation that was unaffected by OGG1 presence. These results indicate that increasing OGG1 content within proliferating NHEK not only repairs the nuclear and mitochondrial oxidative DNA damage and thus prevents the accumulation of 8-oxo-G with UV exposure but also preserves the basal keratinocytes from ssUV-induced cell death and allows more time for DNA repair. In the differentiating keratinocytes destined to be shed off, suppression of caspase-9 activation may be inconsequential and therefore not part of the cellular defense mechanism.
Commercial support: None identified.
Commercial support: None identified.
P2315 Unusual manifestation of noneLangerhans cell histiocytosis an infant with a malabsorption syndrome David Adelson, MD, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Miranda Smith, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
AB110
J AM ACAD DERMATOL
FEBRUARY 2008