Light-skinned Individuals Research Articles

Mechanisms of and variables affecting UVR photoadaptation in human skin.

Humans have been exposed to solar UV radiation since their appearance on Earth and evolution has enabled most individuals to adapt to this exposure, to some degree. UV radiation produces several deleterious effects in human skin and light-skinned individuals are at greatest risk for both acute and long-term negative effects such as DNA damage, sunburn, immune suppression and skin cancer. The benefits of photoadaptation, which leads to a decreased response after acclimatization, are that humans who have skin that is capable of photoadaptation can work and play in the sun with reduced fear of painful sunburn. However, the effects of photoadaptation on DNA damage and development of skin cancer are quite complex and less well-understood. In this article, we have reviewed the current state of knowledge of UVR photoadaptation in human skin. However, more studies are needed to explore the use of UVR photoadaptation to protect against critical endpoints, such as skin cancer.

Skin Tone: An Examination of Trustworthiness and Innocence Among College Students

Skin tone research often addresses the effects of skin tone on prejudice and discriminatory practices. Empirical research has persistently investigated skin tone and its effect on prejudice, discriminatory practices, and sentencing outcomes. Using college students as raters, the present study examined the relationship between skin tone, trustworthiness, and innocence. A total of 139 college students at a Southern University observed 417 photos of capital murderers of varying skin tones to determine whether they appeared to be trustworthy and innocent. The study results revealed that college student raters, regardless of race, were more likely to rate dark-skinned individuals higher on both the trustworthiness and innocence scales than light skin individuals. The current study demonstrated that college students, in comparison to other groups, may respond less negative to skin tone variations.

Juvenile melanomas: Western Australian Melanoma Advisory Service experience.

Juvenile melanoma (before 20 years of age) is a rare condition with poorly defined risk factors. We describe features of juvenile melanoma in Western Australia over the last two decades. A retrospective review of juvenile melanomas was conducted from prospectively maintained databases, reviewed for patients' characteristics, clinical information, histology, treatment, recurrence and survival data. Altogether 95 cases of juvenile melanoma were reported to the Western Australian Cancer Registry between 2000 and 2013. Of these, 27 patients were referred to the Western Australian Melanoma Advisory Service. Over 72% were aged between 13 and 19 years. The most common site for primary melanoma was the head and neck (31.8%). Eight patients (36.4%) had a pre-existing naevus, 13.6% reported 1-5 blistering sunburns in the past and 59.1% had a Fitzpatrick skin grade of 3 or less. Most (88%) were diagnosed with a primary invasive lesion at presentation. Superficial spreading melanomas predominated (27.3%). All but one patient had localised disease at presentation, with six patients undergoing further treatment, including chemotherapy and neck dissection for metastases. At the time of review, two patients had died, due to stroke and metastatic disease. Juvenile melanoma remains a rarity in Western Australia despite a very high incidence of adult melanoma. Unlike in adults, no definitive risk factors have been established. A significant proportion of this cohort had a pre-existing naevus and while most melanomas occurred in sun-exposed areas in light-skinned individuals the association between sunburn and melanoma was not strong.

Melanin reduction by peroxidase activity in lysosome-related organelle extracts from hen egg whites, HeLa cells, and Saccharomyces cerevisiae

Although melanin plays a biological role in the protection of underlying tissues from harmful ultraviolet radiations, yet large amounts of melanin in light-skinned individuals can make them susceptible to skin cancer. In this study, lysosome-related organelles extracts (LOE) from hen egg whites, HeLa cells, and Saccharomyces cerevisiae have been used to lower melanin color intensity. The results show 80% reduction in melanin upon daily treatment with 100 μg LOE for a period of 19 days. Additionally, the treatment with S. cerevisiae LOE showed the best melanin color reduction, which is consistent with the level of peroxidase activity. The treatment of LOE from S. cerevisiae with NH4Cl decreases melanin reduction activity and peroxidase activity compare to LOE from normal S. cerevisiae. Meanwhile, in contrast, the treatment with H2O2 showed a completely contrary pattern. The above results thus indicate that LOEs can be promising agents for use in cosmeceutical skin lightening as well as for the treatment of hyper pigmentation disorders.

Rosacea or Photodamage

The diagnosis of erythematotelangiectatic rosacea (ETR) is complicated by its resemblance to photodamage in light-skinned individuals. To better define

Russell W Brain and the aetiology of multiple sclerosis--a historical perspective

The contribution of British neurologist Russell Walter Brain (1895-1966) to the field of neurology is difficult to overestimate and his seminal work continues to influence modern neurological education and practice. In a landmark review published in the Quarterly Review of Medicine in 1930, he gives a critically important account summarising ideas of the time thought to underlie the then called 'disseminated sclerosis', a disease he notes to be, 'after syphilis, the most frequent disease of the nervous system' in the UK. Across a century and a half, vast progress has been made in attempting to elucidate the as yet unknown cause of MS, which is unravelling to be multifactorial, highly complex and likely dependent on both genetic and environmental risk factors. Brain's observations highlight the changing epidemiology of MS over the last century which are likely to provide the platform in striving towards elucidating MS causation, notably a seemingly reduced latitudinal gradient of MS incidence, an increasing female-to-male sex ratio and an increasing disease rate in dark-skinned compared to light-skinned individuals. In this report we aim to evaluate the relevance today of what we believe to have been an important review demonstrating a perspective on MS far ahead that of its time, with a focus on Brain's ideas on the aetiology of MS; many of which have stood the test of time.

Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment

Studies have established that pigmentation can provide strong, protective effects against certain human diseases. For example, angiogenesis-dependent diseases such as wet age-related macular degeneration and infantile hemangioma are more common in light-skinned individuals of mixed European descent than in African-Americans. Here we found that melanocytes from light-skinned humans and albino mice secrete high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems, including laser-induced choroidal neovascularization, growth factor-induced corneal neovascularization, wound healing, and Matrigel plug assays. Additionally, FMOD enhanced vascular sprouting during normal retinal development. Deletion of Fmod in albino mice resulted in a marked reduction in the amount of neovascularization induced by retinal vein occlusion, corneal growth factor pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for epidemiological differences between light-skinned individuals of mixed European descent and African-Americans. Furthermore, inhibition of FMOD in humans has potential as a therapeutic strategy for treating angiogenesis-dependent diseases.

Histological Basis of Substrate Color-Induced Melanization and Reversal of Melanization in Painted Turtles (Chrysemys picta marginata)

Abstract Crypsis can be facilitated by dynamic color changes that are mediated by chromatophores of the integument. The histological bases of dynamic color changes are well understood for some reptiles, such as lizards, but less so for turtles. We used pixel counts from digital images of tail-tip sections to study histological changes that occur during substrate color-induced melanization, and reversal of melanization, in Midland painted turtles (Chrysemys picta marginata) during 2 companion studies. Melanization in C. picta marginata can be induced in light-skinned individuals when placed on a dark substrate and can be reversed in dark-skinned individuals when placed on a white substrate but without the shedding of scutes. Therefore, we predicted that color change would involve variations in intracellular melanosome concentrations within melanophores, in the deepest living epidermal cells, or both. At hatching, and in individuals that were reared on a white substrate, mean pixel density was relatively lo...

Does artificial UV use prior to spring break protect students from sunburns during spring break?

Dark-skinned individuals are less likely than light-skinned individuals to become sunburned or develop skin cancer. Some have extrapolated this relationship and surmised that developing and maintaining a tan will reduce the risk of sunburns and melanoma. In order to examine whether this strategy indeed protects against sunburns, we surveyed college students about both their tanning habits prior to spring break and their spring break activities. Sorority and fraternity students were recruited after spring break. Analyses examined associations between potential risk factors and the development of one or more sunburns during spring break. As expected, the risk of obtaining a sunburn increased with: time spent in the sun during spring break; light complexion, as assessed by various sun-sensitivity factors; and lack of sunscreen use. We also found that tanning using an artificial UV source during the 10 weeks prior to spring break was not associated with reduced risk of sunburns during spring-break, but rather with a marginal increase in this risk. These data provide evidence that maintaining a tan may not provide protection from sunburns. Public health messages need to address this misconception, stating clearly that a tan does not protect against or reduce the chances of developing a sunburn.

Acromegalic cardiomyopathy in an extensively admixed population: is there a role for GH/IGF‐I axis?

A specific acromegaly-related cardiomyopathy has been described in the literature, largely in Caucasians, which is independent of other risk factors, mainly hypertension. This study assessed the cardiac changes in acromegalics of significant ethnic diversity and also the relevance of the aetiopathogenic factors involved, such as disease activity and hypertension. It is a cross-sectional study with a comparative control group. In this study, 37 acromegalic patients (20 Intermediate-skinned (IS), 14 Dark-skinned (DS) and three Light-skinned (LS) individuals) and 74 controls matched by age, gender and hypertension were evaluated. Cardiac morphology and function were addressed using echocardiography parameters. The mean age of patients was 46.9 ± 12.8 years, with 67.6% being women and 43.2% hypertensive. The prevalence of left ventricular hypertrophy (LVH) between acromegalics was 56.8% vs 10.8% in the controls (P < 0.001). About 86% of patients with LVH had active disease (P = 0.023). Logistic regression revealed that disease activity presented a stronger association (OR = 5.925; CI = 1.085-32.351; P = 0.040) with LVH than hypertension (OR = 3.237; CI = 0.702-14.924; P = 0.132). When DS acromegalics were compared with IS ones, no statistically significant differences were observed. Chronically hyperactive somatotropic axis remains as an independent and determining factor in the development of left ventricular hypertrophy, as it is more associated with this condition than hypertension in a largely admixed population with a high degree of African ancestry.

Lichen planus pigmentosus-inversus: Case report and review of an unusual entity

Lichen planus pigmentosus-inversus is a rare variant of lichen planus, with less than 20 cases reported in the medical literature. It presents as asymptomatic to mildly pruritic, hyperpigmented macules and/or patches involving intertriginous and flexural areas and skin folds in light-skinned individuals. The unique pattern of skin involvement, clinical features, and histology are distinctive. The combination of hyperpigmented lesion(s) isolated to non-sun exposed, intertriginous, and flexural areas with lichenoid histology is unique and separates it from other similar entities, such as lichen planus actinus and erythema dyschromicum perstans/ashy dermatosis. The case well highlights this unusual condition and represents the first case reported in the United States.

Vitamin D in the New Millennium

The incidence of vitamin D deficiency is rising worldwide, yet in the vast majority of patients, the condition remains undiagnosed and untreated. Current evidence overwhelmingly indicates that supplemental doses greater than 800IU/day have beneficial effects on the musculoskeletal system, improving skeletal homeostasis, thus leading to fewer falls and fractures. Evidence is also accumulating on the beneficial effects of vitamin D on extraskeletal systems, such as improving immune health, autoimmune disorders, cancer, neuromodulation, diabetes, and metabolic syndrome. The cause-effect relationship of vitamin D deficiency with increasing incidences of nonskeletal disorders is being investigated. Published reports support the definition of sufficiency, serum levels of 25-hydroxyvitamin D [25(OH)D] greater than 30ng/mL (75nmol/L). To achieve this, most people need vitamin D supplementation ranging from 600 to 2000IU/day; consumption up to of 5000 international units (IU) per day of vitamin D is reported as safe. Although light-skinned individuals need 1000IU/day of vitamin D, elderly and dark-skinned individuals are likely to need approximately 2000IU/day to maintain serum 25(OH)D levels greater than 30ng/mL. Other vulnerable patients, such as the obese, those who have undergone bariatric surgery, and those with gastrointestinal malabsorption syndromes, may require higher doses of vitamin D to maintain normal serum levels and be healthy.

Blurred Borders for Some but Not “Others”: Racialization, “Flexible Ethnicity,” Gender, and Third-Generation Mexican American Identity

How are the lives of middle-class third-generation Mexican Americans both racialized and gendered? Third-generation Mexican Americans in California experience a racialization process continuum that extends from “flexible ethnicity,” the ability to be considered an “insider” in different racial/ ethnic communities, to racialization as nonwhite that is enforced through the deployment of negative stereotypes. Using interview data, the author finds that women are afforded more “flexible ethnicity” than men. Accordingly, men are more rigorously racialized than women. Women are racialized through exoticization, whereas men are racialized as threats to safety. Lighter-skinned individuals escaped consistent racialization. These findings have consequences for the incorporation possibilities of later-generation Mexican Americans, as women and light-skinned (often multiracial) individuals are more frequently granted “flexible ethnicity” and less strongly racialized than men and dark-skinned (often monoracial) individuals. Even among the structurally assimilated, contemporary racial and gender hierarchies limit the voluntary quality of ethnicity among third-generation Mexican Americans.

Skin Malignancies Associated with HYDROXYUREA Use in MYELOPROLIFERATIVE DISORDERs and Sickle Cell Patients: Incidence and Significance.

Abstract 4969 BACKGROUNDHydroxyurea (HU) is one of the mainstay agents used to treat myeloproliferative disorders as well as sickle cell anemia. There has been lately increasing reports of secondary skin malignancies in patients receiving Hydroxyurea therapy but the literature consists essentially of case reports. Current incidence of melanoma skin cancer in the general population in the United States is 15 per 100 000 person, and of non melanoma skin cancer is 230 per 100 000 lightly pigmented individuals and 3.4 per 100 000 darkly pigmented individuals. METHODSWe reviewed 292 charts of patients treated with HU in our institution. 237 patients carried a diagnosis of myeloproliferative disorder, 14 patients were treated for sickle cell anemia and 41 patients were being treated with HU for HIV as part of a regimen to decrease viral load. Charts were reviewed looking for development of skin malignancies. RESULTSAmong the patients with sickle cell anemia, the incidence of skin cancer was nil. Among the patients with HIV there were 2 cases of non melanoma skin cancer. Among patients with myeloproliferative disorders, there were 16 cases of skin cancer. The pathology was non-melanoma skin cancer. Subgroup analysis based on skin phenotype revealed that the incidence was higher than the general population in both dark and light-skinned individuals: the rate was 0.9434 per 100 among the dark skinned individuals, statistically significant when compared to the established rate of 0.0034 per 100 dark-skinned individual in the general population. Similarly among light-skinned individuals, the calculated rate was 12.0968 per 100-person, which is statistically significant compared to the rates in light-skinned individuals in the general population of 0.2300 per 100 person with a p-value of 0.001. CONCLUSIONOur study showed a significantly higher incidence of non-melanoma skin cancer among patients treated with HU. While HU is well known to have cutaneous side effects in terms of hyperpigmentation, skin ulcers, scaling or skin atrophy, its implication in skin cancers had only been in the form of case reports. Our study thus highlights a true risk of skin malignancies with HU. It is worth noting though that there were only non-melanoma skin cancers, which are non-aggressive, localized and treatable. Thus this heightened incidence of skin cancer does not appear to bear a mortality or morbidity burden on patients treated with HU. DisclosuresNo relevant conflicts of interest to declare.

Volar Melanotic Macules in a Gardener: A Case Report and Review of the Literature

Volar melanotic macules are asymptomatic, tan-brown to brownish-black macules found on the palms, fingers, soles, and/or toes of dark-skinned individuals and are infrequently reported in light-skinned individuals. Herein, we report the acquisition of multiple, brownish-black volar digital macules in a 63-year-old white woman and avid gardener that were noted after the onset of pruritic, chronic hand dermatitis over a 10-month period. She was healthy without any medical conditions or medications. No family history of intestinal polyposis or mucosal melanosis existed. At presentation, she had less than 20 brownish-black, 2- to 10-mm irregular macules over the volar aspect of the thumbs and index fingers, left greater than right hand, associated with erythema, scale, and a negative potassium hydroxide examination. In addition, she had melanotic macules of her lips, buccal mucosa, and conjuctiva. No nail or anogenital macules were found. Biopsy demonstrated a region of epidermal hyperplasia, hyperkeratosis, and interface dermatitis associated with melanophages and sparse lymphocytic infiltrate. Melanin staining revealed diffuse pan-epidermal hypermelanization, dermal melanin, and dendritic melanocytes, which expressed HMB-45. After 1-year follow-up and treatment with topical corticosteroid, the volar macules have faded to tan brown. Based on the location, avocation, and coexisting mucosal melanotic macules, an irritant phytodermatitis with postinflammatory hyperpigmentation was diagnosed in the setting of Laugier-Hunziker syndrome-a disorder denoted by macular hyperpigmentation of nail, volar, and/or mucosal surfaces in healthy adults. Volar melanotic macules can also complicate 5-flourouracil therapy, tinea pedis, and other inflammatory disorders; be associated with acral melanomas; or represent a cutaneous manifestation of systemic disease such as Addison disease, Peutz-Jegher syndrome, Leopard syndrome, Carney syndrome, AIDS, and neurofibromatosis.

Ultraviolet Radiation Exposure, Vitamin D, and Cancer

This paper reviews briefly the evidence for an association between various measures of UV radiation (UVR) exposure and the development of cancer. Issues such as data quality, study design, measurement variation, comparability of studies, and quantification of UV exposure in relation to skin cancer are discussed. A range of exposure, based on skin type, might be appropriate: from 5 min a day three times a week for light-skinned individuals and 10 min a day three times a week for darker-skinned individuals. These exposures translate into 13 h per year, for a light-skinned individual, leading to 650 h of exposure from birth to age 50.

Can diet prevent nonmelanoma skin cancer progression?

Nonmelanoma skin cancer is the most prevalent malignant disease among light-skinned individuals in the USA, accounting for approximately 1 million new cases annually. Solar ultraviolet radiation is known to be the major cause of skin cancer. The idea that diet, particularly dietary fat, may play a role in modulating cancer incidence has been based largely upon indirect epidemiologic evidence. However, few studies have found correlations of dietary fat intake with skin cancer incidence. Nevertheless, a large body of evidence with experimental animals and one clinical intervention trial, the latter avoiding the pitfalls of many epidemiologic investigations, clearly demonstrate that the level of dietary fat intake can have a significant influence on the occurrence of skin cancer in individuals at high risk.

Evaluation of single versus multiple cryogen spray cooling spurts on in vitro model human skin

Many commercially available dermatologic lasers utilize cryogen spray cooling for epidermal protection. A previous tissue culture study demonstrated that single cryogen spurts (SCS) of 80 ms or less were unlikely to cause cryo-injury in light-skinned individuals. More recently, multiple cryogen spurts (MCS) have been incorporated into commercial devices, but the effects of MCS have not been evaluated. The aim was to study an in vitro tissue culture model and the epidermal and dermal effects of SCS vs patterns of shorter MCS with the same preset total cryogen delivery time (Deltat(c)) and provide an explanation for noted differences. Four different spurt patterns were evaluated: SCS: one 40-ms cryogen spurt; MCS2: two 20-ms cryogen spurts; MCS4: four 10-ms cryogen spurts; MCS8: eight 5-ms cryogen spurts. Actual Deltat(c) and total cooling time (Deltat(Total)) were measured for each spurt pattern. RAFT tissue culture specimens were exposed to cryogen spurt patterns and biopsies were taken immediately and at days 3 and 7. Actual Deltat(c) was increased while Deltat(Total) remained relatively constant as the preset Deltat(c) of 40 ms was delivered as shorter MCS. Progressively more epidermal damage was noted with exposure to the MCS patterns. No dermal injury was noted with either SCS or MCS. For a constant preset Deltat(c) of 40 ms, delivering cryogen in patterns of shorter MCS increased the actual Deltat(c) and consequently the observed epidermal cryo-injury as compared to an SCS.

DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency

Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.

Gli proteins up-regulate the expression of basonuclin in Basal cell carcinoma.

Tumorigenesis is frequently accompanied by enhanced rRNA transcription, but the signaling mechanisms responsible for such enhancement remain unclear. Here, we report evidence suggesting a novel link between deregulated Hedgehog signaling and the augmented rRNA transcription in cancer. Aberrant activation of the Hedgehog pathway in keratinocytes is a hallmark of basal cell carcinoma (BCC), the most common cancer in light-skinned individuals. We show that Gli proteins, downstream effectors of the Hedgehog pathway, increase expression of a novel rRNA gene (rDNA) transcription factor, basonuclin, whose expression is markedly elevated in BCCs. The promoter of the human basonuclin gene contains a Gli-binding site, which is required for Gli protein binding and transcriptional activation. We show also that the level of 47S pre-rRNA is much higher in BCCs than in normal epidermis, suggesting an accelerated rRNA transcription in the neoplastic cells. Within BCC, those cells expressing the highest level of basonuclin also exhibit the greatest increase in 47S pre-rRNA, consistent with a role for basonuclin in increasing rRNA transcription in these cells. Our data suggest that Hedgehog-Gli pathway enhances rRNA transcription in BCC by increasing basonuclin gene expression.