Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultraviolet B (UVB) irradiation has extensively been advocated for use in the investigation of cutaneous inflammation in vivo. Mostly doses above the threshold of skin damage have been used. Therefore it is not clear whether the changes observed are specific effects of UVB or to a certain extent represent wound healing. In this study the dose-dependent effects of UVB on normal human skin were assessed using histology and immunohistochemistry. The dose of 1 MED was chosen as a dose unducing tissue changes with adequate morphology: no toxicity but evident immunohistochemical changes. The sequential effects of this 1 MED of UVB were studied for up to 14 days after irradiation, using immunohistochemistry with a panel of monoclonal antibodies. Substantial effects were observed, mainly on proliferation and differentiation; the markers for inflammation did not reveal major changes. This model might be a promising approach to evaluate the effect of drugs on epidermal proliferation and differentiation in vivo.
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PMID:The immunohistochemical effects of a single challenge with an intermediate dose of ultraviolet B on normal human skin. 887 44

Glutathione S-transferases (GSTs) play a primary role in cellular defense against electrophilic chemical species and radical oxygen species. Because free radical attack is one mechanism of UV irradiation-caused skin damage, we investigated whether genetic variation at the GST loci GST T1 and GST M1 influences individual UVB sensitivity. In a double-blind clinical trial, 50 healthy volunteers were evaluated for minimal erythema dose of UVB irradiation, MED (J/cm2), skin types were assigned, and internal standard-controlled polymerase chain reaction (PCR) was used to identify their GST T1 and GST M1 genotypes. The five homozygous carriers of the GST T1 deletion (GST T1*0/0) presented with the most intensive inflammatory reactions after irradiation; they were significantly overrepresented among the highly UVB-sensitive subgroups (p = 0.006). Lack of GST M1 (GST M1*0/0, n = 27) tended to be more frequent only in UVB-sensitive subjects, and the proportion of the active GST M1 allelic variants *A and *B was similar in all UVB sensitivity subgroups. Three subjects with deficiencies in GST T1 and GST M1 had the most intense inflammatory responses. No effect of gender or genetic variations at the MC1R gene locus was established. Thus, heritable GST T1 deficiency may be a genetic determinant of individual skin sensitivity toward UV irradiation.
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PMID:Deficiency of glutathione S-transferases T1 and M1 as heritable factors of increased cutaneous UV sensitivity. 900 40

Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)-induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA-PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA-PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53-positive cells was found in areas protected with the sunscreen having the higher UVA-PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320-400 nm) or UVA1 (340-400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53-positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA-induced cell damage.
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PMID:Accumulated p53 protein and UVA protection level of sunscreens. 1072 57

UV-induced skin damage is the result of a complex cascade of events. Many studies have focused on the skin effects induced by UV-B or UV-A separately. Recently a UV-source that emits UV-B and UV-A together in a ratio comparable to daily sunlight has been introduced: i.e. solar simulated radiation (SSR). By exposing human skin type I-III to erythematogenic doses of UV (> or =1 MED) emitted by a SSR source we have noticed that: (a) neutrophils are initially the main infiltrating cell type in the dermis and (b) these infiltrating cells are the a key source of in vivo enzymatically [corrected] active enzymes such as elastase, [corrected] matrix metallo proteinases-1 and -9 (MMPs-1 and -9). These enzymes are relevant to the process of photoaging, as they break down the extracellular matrix. Keratinocytes and fibroblasts also produce matrix degrading enzymes, but to a lesser extent. Our results indicate a primary role for infiltrating neutrophils in the initial steps of photoaging. This is further supported by the observation that after exposure of skin type VI to physical doses of SSR, equivalent to those used for skin types I-III, no neutrophils and neutrophil-derived enzymatic activity were observed, explaining why skin type VI is [corrected] less susceptible to photoaging than skin types [corrected] I-III. Statement: Although most of the data, referred to, have been published, the current perspective in which they are put together is completely novel and has not been published elsewhere.
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PMID:Pathophysiology of photoaging of human skin: focus on neutrophils. 1646 4

Acute exposure to UV radiation (UVR) causes visible skin damage such as erythema and results in local and systemic immunosuppression while chronic exposure can result in photocarcinogenesis. These deleterious effects can be quantified by histology and by bioassays of key biological markers, including matrix metalloproteinases (MMPs), or tryptophan moieties. We now report our results in quantifying UV skin damage with noninvasive optical methods based on reflectance and fluorescence spectroscopy and compare these noninvasive measurements to histopathology and MMP-13 expression. A solar simulator with spectral output nearly identical to that of solar radiation was developed and used in our experiments. SKH1 hairless mice were exposed to solar-simulated UVR at a total dose of 21 MED delivered over 10 weeks. Changes in oxygenated and deoxygenated hemoglobin were measured by diffuse reflectance spectroscopy, and tryptophan changes were monitored via a fluorescence monitor. Our results show that there is an increase in erythema, skin fluorescence, sunburn cells and MMP-13 after a series of suberythemal doses of UV irradiation on a hairless mouse animal model. Increased skin fluorescence is observed with increasing UV exposure. The levels of MMP-13 increase as the cumulative UV dose increases but their increase does not correspond to noninvasively measured changes.
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PMID:Noninvasive assessment of UV-induced skin damage: comparison of optical measurements to histology and MMP expression. 1990 94