The detrimental effects of daily sub-erythemal exposure on human skin in vivo can be prevented by a daily-care broad-spectrum sunscreen.
Explore the source record for details and available documents.
Drug Administration Schedule↗
Biomedical subjects
Antony R Young
Publications and source records attributed to Antony R Young.
Acute effects of UVR on human eyes and skin.
Solar UVR ( approximately 295-400 nm) has acute clinical effects on the eyes and the skin. The only effect on the eye is inflammation of the cornea (photokeratitis), which is caused by UVB (and non-solar UVC) and resolves without long-term consequences within 48 h. The effects on the skin are more extensive and include sunburn (inflammation), tanning and immunosuppression for which UVB is mainly responsible. Tanning is modestly photoprotective against further acute UVR damage. Skin colour is also transiently changed by UVA-dependent immediate pigment darkening, the function of which is unknown. Skin type determines sensitivity to the acute and chronic effects of UVR on the skin. Some of the photochemical events that initiate acute effects are also related to skin cancer. Solar UVB is also responsible for the synthesis of vitamin D.
Acute Disease↗
Photoadaptation during narrowband ultraviolet-B therapy is independent of skin type: a study of 352 patients.
Understanding how photoadaptation differs between individuals is important when considering susceptibility to the beneficial and harmful effects of sunlight exposure and when determining optimal phototherapy regimens. Most narrowband UVB (NB-UVB) regimens start with 70% of the minimal erythema dose (MED) with 20% increments at each treatment thereafter. We retrospectively studied 352 skin types I-IV psoriatic patients having twice weekly treatment with this regimen. Patients with high skin types tended to have high MEDs (P<0.001). By session 20 the proportion of patients who had developed erythema was approximately 60% regardless of MED. Among patients who developed erythema, the number of treatments before erythema occurred did not differ between skin types (P=0.33). We conclude that patients with high skin types photoadapt approximately equally per physical unit of UVR in comparison to those with low skin types, but they have greater photoadaptation in absolute terms because they are able to tolerate a higher initial dose of radiation. Differences in skin type or MED are not associated with clinically important differences in tendency to erythema during a standard 70/20% NB-UVB twice-weekly regimen. This regimen is suitable for all skin types I-IV patients regardless of skin type or MED.
Adaptation, Physiological↗
Melanogenesis: a photoprotective response to DNA damage?
Exposure to ultra violet radiation (UVR) is associated with significant long-term deleterious effects such as skin cancer. A well-recognised short-term consequence of UVR is increased skin pigmentation. Pigmentation, whether constitutive or facultative, has widely been viewed as photoprotective, largely because darkly pigmented skin is at a lower risk of photocarcinogenesis than fair skin. Research is increasingly suggesting that the relationship between pigmentation and photoprotection may be far more complex than previously assumed. For example, photoprotection against erythema and DNA damage has been shown to be independent of level of induced pigmentation in human white skin types. Growing evidence now suggests that UVR induced DNA photodamage, and its repair is one of the signals that stimulates melanogenesis and studies suggest that repeated exposure in skin type IV results in faster DNA repair in comparison to skin type II. These findings suggest that tanning may be a measure of inducible DNA repair capacity, and it is this rather than pigment per se which results in the lower incidence skin cancer observed in darker skinned individuals. This evokes the notion that epidermal pigmentation may in fact be the mammalian equivalent of a bacterial SOS response. Skin colour is one of most conspicuous ways in which humans vary yet the function of melanin remains controversial. Greater understanding of the role of pigmentation in skin is vital if one is to be able to give accurate advice to the general public about both the population at risk of skin carcinogenesis and also public perceptions of a tan as being healthy.
DNA↗
Measurement of sunscreen immune protection factors in humans: a consensus paper.
It is increasingly accepted that sunscreens should protect against ultraviolet radiation (UVR)-induced immunosuppression, with an index of protection that can be compared with the sun protection factor (SPF). Five groups of immunoprotection researchers met to discuss the status of immune protection factor (IPF) evaluation in human skin in vivo. Current methods rely on a suncreen's inhibition of UVR-induced local suppression of the contact hypersensitivity (CHS) response or the delayed-type hypersensitivity (DTH) response, using either the induction or the elicitation arms of these responses. The induction arm of the CHS response has the advantage of being sensitive to a single sub-erythemal exposure of solar-simulating radiation (SSR) that allows a direct comparison with the SPF. This approach, which necessitates sensitization, requires a large number of volunteers and is too labor intensive and time consuming to become a routine method. The elicitation arm of the CHS or DTH responses exploits prior sensitization to contact or recall antigens and has the advantage of being possible to apply on small groups of volunteers. Some current protocols, however, require repeat SSR exposures, which invalidates a direct comparison with SPF that is based on a single exposure. There is a need for a new simpler method of IPF that will have to be validated against existing models.
Dermatitis, Contact↗
Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation.
A wide range of piperine analogues has been synthesised in order to undertake a structure-activity study of their ability to stimulate melanocyte proliferation. Results demonstrate that an aromatic ring containing at least one ether function and a carbonyl group containing side chain is essential for this activity. A number of highly active piperine analogues have been identified, for instance 1-(3,4-methylenedioxyphenyl)-penta-2E,4E-dienoic acid methyl ester (5a), 1-E,E-piperinoyl-isobutylamine (4f) and 1-(3,4-methylenedioxyphenyl)-pentanoic acid cyclohexyl amide (20). A selection of analogues has also been evaluated for their effect on melanocyte morphology and melanogenesis. The piperine analogues altered cell morphology by increasing dendrite formation leading to bi-, tri- and quadripolar cells. These same analogues were found to increase total melanin in cell cultures, although melanin content per cell was not significantly altered from control in the presence of these compounds.
Alkaloids↗
An optimal method for experimental provocation of polymorphic light eruption.
BACKGROUND: There is controversy about the best method to induce polymorphic light eruption (PLE) experimentally. Objectives To review articles on PLE induction and design a UV radiation protocol that improves success rates with clinically relevant doses of environmentally relevant solar-simulated radiation (SSR). DESIGN AND SETTING: All articles on the experimental provocation of PLE published since 1980 were reviewed. Photoprovocation of lesions was studied in 25 PLE patients. The 24-hour minimal erythemal dose (MED) of SSR was determined. Thereafter, six 4 x 4-cm adjacent sites on previously affected and previously unaffected skin were exposed to 0.25, 0.5, 0.75, 1.0, 1.25, 1.5 MED of SSR for 3 to 4 consecutive days. The study periodwas autumn to spring in London, England (51 degrees north latitude). MAIN OUTCOME MEASURES: Relationship between PLE induction and biological and physical exposure parameters. CONCLUSIONS: The review shows that fractionated erythemally effective UV-A exposures were more successful than single-sunburning UV-B doses. Photoprovocation of PLE was successful in 68% of patients after 2 to 3 SSR exposures that were not necessarily erythemal. There was no difference in success rate between previously affected and previously unaffected skin. Our data indicate that PLE is more likely to be induced when the natural causes of the disease are simulated.
Clinical Trials as Topic↗
Ultraviolet radiation-induced inflammation as a model for cutaneous hyperalgesia.
The effects of UVA-I and solar simulated radiation on skin sensitivity to thermal and mechanical stimuli were compared in normal volunteers. Individual minimal erythema doses (MED) for each source were determined and previously unexposed buttock skin was exposed to 1, 2 and 3 MED of each spectrum. Erythema, and mechanical and thermal pain thresholds were quantified from 3 to 72 hours post-irradiation. Irradiated skin did not exhibit pain but hyperalgesia and allodynia were provoked by the applied stimuli after exposure to 2 or 3 MED. There were highly significant decreases in thresholds for both stimuli in exposed skin compared with non-exposed skin. These changes began within a few hours of irradiation, peaked about 24 hours later and persisted throughout the test period. The sensitivity changes broadly followed the erythema response and did not extend beyond the irradiated area. There were only minor differences between the two spectra at comparable erythemal doses. These data demonstrate the usefulness of UVR-induced inflammation as a model of cutaneous hypersensitivity. This model has clinical relevance for the study of hyperalgesia in general and the abnormal sensitivity of sunburnt skin in particular. It is likely to be useful in the assessment of peripherally acting analgesic drugs.
Adult↗
Ultraviolet-radiation-induced erythema and suppression of contact hypersensitivity responses in patients with polymorphic light eruption.
Ultraviolet-radiation suppresses cell-mediated immunity in healthy humans. It has been postulated that, in the short term, this immunosuppression prevents autoimmune responses to ultraviolet-radiation damaged skin. Patients with polymorphic light eruption (PLE) demonstrate abnormal responses to ultraviolet-radiation suggestive of an immune response to an ultraviolet-radiation-induced antigen. We investigated whether PLE patients (n=22) were resistant to ultraviolet-radiation-induced immunosuppression compared to skin-type, aged-matched controls (n=23). Groups of patients and controls (six subjects per group) received a single dose of solar-simulated ultraviolet-radiation of either 0, 0.6, 1 or 2 minimal erythema doses (MED). Erythema was quantified using a reflectance meter and all volunteers were sensitised on the irradiated site with dinitrochlorobenzene. Contact hypersensitivity responses (CHS) to dinitrochlorobenzene were quantified after challenge using ultrasound. Ultraviolet-radiation-induced erythema was comparable in patients and controls. CHS was comparable in unirradiated patients and controls. UVR-induced a dose-dependent suppression of CHS in all volunteers but patients were more resistant to immunosuppression after 1MED. Exposure to 1MED suppressed CHS by 78% in controls but induced less suppression in patients (44%, p < 0.01). Our data suggest that PLE patients have a flaw in their immunoregulatory response to ultraviolet-radiation it is only apparent over a narrow dose range around 1 MED.
Adult↗
Tanning devices--fast track to skin cancer?
The use of UVB and/or UVA emitting devices for cosmetic tanning is widespread in Western populations including young people and is especially prevalent in females. Several epidemiological studies, although not all, have shown a significant relationship between the use of tanning devices and malignant melanoma after, in some cases, adjustment for confounding factors such as solar ultraviolet radiation (UVR) exposure. A relationship between solar exposure, especially intermittent exposure, and malignant melanoma is well established so it is not surprising that a similar connection has been reported for the use of tanning devices. Several epidemiological studies show that childhood exposure to sunlight is a risk factor for malignant melanoma and this may also be the case for the use of tanning devices, especially if sunburns are obtained. Some studies have evaluated the relationship between the use of tanning devices and non-melanoma skin cancer and at least one has suggested an association. The use of tanning devices by a substantial minority of young people is a worrying trend in terms of a likely increased incidence of malignant melanoma, and possibly non-melanoma cancers in the future. Although two recent reviews by epidemiologists conclude that a clear link between tanning devices and malignant melanoma is yet to be proven, there is a strong case for effective legislation to prohibit the use of tanning devices by people under 18 yr of age.
Beauty Culture↗
Methods used to evaluate the immune protection factor of a sunscreen: advantages and disadvantages of different in vivo techniques.
Solar UV radiation (UVR) induces skin cancer in humans, a process partially mediated by UVR-induced immunosuppression. To help prevent skin cancer, sunscreens should prevent UVR-induced immunosuppression to a level that is comparable to their sun protection factor (SPF). There are no standardized protocols for determining the immune protection factor (IPF) of sunscreens or agreement on what degree of IPF is needed to fully preserve cutaneous immune function. Current in vivo approaches to this problem rely on sunscreens' ability to prevent localized UVR-induced suppression of contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH) responses, using either the induction or elicitation arms of these responses, with comprehensive controls. The induction arm of the CHS response is sensitive to a single suberythemal exposure of solar-simulated radiation (SSR), and allows for direct SPF and IPF comparisons. However, this approach requires a large number of volunteers and is extremely labor-intensive and time-consuming. The elicitation arm of the CHS or DTH response exploits prior sensitization to contact or recall antigens. Fewer volunteers are needed, but current protocols require repeat SSR exposure, which may invalidate comparison with SPF measures based on a single exposure, or erythemal doses, which may have systemic effects. Robust protocols for routinely assessing IPF are needed.
Allergens↗
Proceedings from a clinical roundtable.
Explore the source record for details and available documents.
Humans↗
Standardized protocols for photocarcinogenesis safety testing.
Solar ultraviolet radiation (UVR) is recognized as a major cause of non-melanoma skin cancer in man. Skin cancer occurs most frequently in the most heavily exposed areas and correlates with degree of outdoor exposure. The incidence of skin cancer is also increased by contact with photosensitizing drugs and chemicals such as psoralens, coal tars and petroleum stocks. Other substances which do not act as photosensitizers, such as immunosuppressants taken by organ transplant recipients, also increase the risk of skin cancer. The U.S. Food and Drug Administration requests, on a case-by-case basis, that risk of enhanced photocarcinogenesis is assessed for many classes of drugs. Health Canada's Therapeutic Products Programme has issued a Notice of Intent to regulate pharmaceutical products which may enhance carcinogenicity of the skin induced by ultraviolet radiation. Other national regulatory agencies review such data when they exist, but their own requirements emphasize batteries of short-term in vitro and in vivo tests. While they may support drug development strategies, short-term tests have yet to be validated as predictors of the ability of drugs or chemicals to enhance photocarcinogenesis. Published protocols now describe study designs and procedures capable of determining whether test agents enhance the rate of formation of UVR-induced skin tumors.
Animals↗
A commercial sunscreen's protection against ultraviolet radiation-induced immunosuppression is more than 50% lower than protection against sunburn in humans.
Ultraviolet radiation (280-400 nm)-induced suppression of cutaneous cell-mediated immunity plays an important part in the development of skin cancer. Sunscreens are widely advocated to protect against skin cancer but if they offer insufficient protection against immunosuppression they may inadvertently increase skin cancer risk. This human study evaluated immunoprotection afforded by a commercial sunscreen preparation (labeled sun protection factor 15) offering primarily ultraviolet B (280-320 nm) protection. Indirectly, it also investigated whether ultraviolet A (320-400 nm) plays a part in ultraviolet radiation-induced immunosuppression. Healthy white-skinned volunteers were used (n=119). Ultraviolet radiation exposures were on previously unexposed buttock skin with an ultraviolet radiation source that complied with European recommendations for sunscreen testing. Ultraviolet radiation dose-response curves for sunburn/erythema and suppression of the contact hypersensitivity response were generated either with or without sunscreen in vivo and protection factors were derived for both end-points. The ultraviolet radiation wavelengths transmitted by the sunscreen were determined in vitro and showed that the sunscreen was primarily an ultraviolet B absorber, with relatively poor absorption in the ultraviolet A region. The sun-screen protected against both erythema and immunosuppression but protection against immunosuppression (IPF=4.9, 95% confidence interval: 2.3-10.6) was less than half that for erythema (Ery-PFg=14.2, 95% confidence interval: 10.2-19.8). Failure of the sunscreen to afford comparable protection against both end-points was probably due to immunosuppression by ultraviolet A, a part of the solar spectrum that does not readily cause sunburn. The sunscreen protected against both end-points, which supports the use of sunscreens to reduce immunosuppression but protection against immunosuppression may be improved if sunscreens are formulated to offer equivalent protection against ultraviolet B and ultraviolet A.
Adolescent↗
Are broad-spectrum sunscreens necessary for immunoprotection?
Explore the source record for details and available documents.
Animals↗
Ultraviolet radiation-induced erythema in human skin.
We have evaluated UVR-induced erythema in previously unexposed buttock skin of volunteers of skin types I, II, III, and IV. Studies were done with solar-simulated radiation (SSR), UVB, and UVAI and we determined the just perceptible minimal erythema dose (MED) and, in some cases, quantified erythema with a reflectance device. The results show that there is a trend for increased SSR MED with skin type, with the MED of skin type IV being approximately twice that of skin type I, a smaller difference than one might have expected. However, there is a very considerable overlap of MED between skin types which shows that MED is a very poor indictor of skin type. Quantitative dose-response and time course studies with SSR and UVAI showed broadly similar responses when comparable MED-based exposures were given. We used our data to test the new concept of the standard erythema dose (SED) with two different erythema action spectra, and confirmed that the SED approach works with the different UVR sources that we studied.
Dose-Response Relationship, Radiation↗
Effects of solar simulated radiation on the human immune system: influence of phototypes and wavebands.
We have shown that skin-types I/II are much more susceptible to UVR-induced suppression of the induction phase of contact hypersensitivity than skin-types III/IV. Studies with a UVB sunscreen have provided indirect evidence that UVA is more immunosuppressive than it is erythemogenic. Overall, our studies show a lack of direct correlation between erythema and immunosuppression.
Humans↗
The sunburn cell revisited: an update on mechanistic aspects.
The sunburn cell (SBC), with its pyknotic nucleus and eosinophilic cytoplasm, is characteristic of mammalian epidermis after exposure to UVC and UVB radiation or UVA radiation in the presence of psoralens. SBC may be regarded as an example of apoptosis: controlled individual cell death. Since the discovery of apoptosis over thirty years ago, there has been a considerable increase in the knowledge of mechanisms involved in this process. DNA damage has been shown to be a major determinant of SBC production both in a p53-dependent and -independent manner. Extranuclear events such as activation of membrane bound death receptors also contribute to SBC formation. The development of new technologies and techniques has resulted in a better understanding of the mechanisms and machinery involved in apoptosis, triggered by various stimuli and in different cell types. Of particular importance has been the elucidation of regulatory molecules such as caspases, inhibitor of apoptosis proteins (IAP) and the role of mitochondria as key to the process of apoptosis and consequent production of SBC. This review attempts to give an update on those mechanisms involved and the occurrence and relevance of SBC in mammalian skin are discussed.
Animals↗