Porokeratosis: An enigma beginning to unravel.

Porokeratosis is a keratinization disorder with unclear etiopathogenesis, varied clinical presentation and characteristic histopathology, and is usually unresponsive to current therapeutic options. Until now, it was considered to be a clonal disorder with immunity, ultra violet radiation and other factors playing important roles in etiopathogenesis. It is now known that abnormalities in the mevalonate pathway are responsible for this clonal keratinization abnormality. New variants of porokeratosis like eruptive bullous, pruriginous, lichen planus like, follicular variants and porokeratoma have been described. While the cornoid lamella is the classical histopathologic feature, dermoscopy and reflectance confocal microscopy make the diagnosis clearer. Development of malignancy in a few variants is a concern. Linear, disseminated superficial actinic and giant lesions are most prone to developing malignancies. Bowen's disease, squamous cell carcinoma, basal cell carcinoma and even melanoma have been reported in cases of long-standing porokeratosis. Newer modalities of therapy such as photodynamic therapy, ingenol mebutate and HMGCoA inhibitors may play a role in the future.

On-Demand Reversible UV-Triggered Interpenetrating Polymer Network-Based Drug Delivery System Using the Spiropyran-Merocyanine Hydrophobicity Switch.

A reversible switchable on-demand UV-triggered drug delivery system (DDS) based on interpenetrating polymer networks (IPNs) with silicone as the host polymer and spiropyran (SP)-functionalized guest polymer is designed and demonstrated. The photo-responsive IPNs provide a new triggered drug delivery concept as they exploit the change in intermolecular interactions (work of adhesion) among the drug, matrix, and solvent when the incorporated hydrophobic SP moieties transform into the hydrophilic merocyanine form upon light irradiation without degradation and disruption of the DDS. The change in how the copolymer composition (hydrophilicity and content) and the lipophilicity of the drug (log P) affect the release profile was investigated. A thermodynamic model, based on Hansen solubility parameters, was developed to design and optimize the polymer composition of the IPNs to obtain the most efficient light-triggered drug release and suppression of the premature release. The developed IPNs showed excellent result for dopamine, l-dopa, and prednisone with around 90-95% light-triggered release. The model was applied to study the release behavior of drugs with different log P and to estimate if the light-induced hydrophobic-to-hydrophilic switch can overcome the work of adhesion between polymers and drugs and hence the desorption and release of the drugs. To the best of our knowledge, this is the first time that work of adhesion is used for this aim. Comparing the result obtained from the model and experiment shows that the model is useful for evaluating and estimating the release behavior of specific drugs merocyanine, IPN, DDS, and spiropyran.

To determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol in a North Indian location.

BACKGROUND: Psoralen with ultraviolet A is an effective photochemotherapeutic modality. A subtype of this, PUVAsol, uses sunlight as the natural source of ultraviolet A. The amount of sunlight received and the consequent ultraviolet A exposure vary according to the month in the year, time of the day and geographical location of a place. AIM: The aim of this study is to determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol. MATERIALS AND METHODS: This was an observational study carried out at Postgraduate Institute of Medical Education and Research, Chandigarh (30.7333°N, 76.7794°E), India using a photometer. Ultraviolet A irradiance was recorded at a fixed place at 10 AM, once weekly for a period of 12 months. RESULTS: The irradiance of peak ultraviolet A was found to be 3.1 mW/cm2 in June 2016 while irradiance of 0.64 mW/cm2 was recorded in January 2017. The exposure time needed for therapeutic dose of 2 J/cm2 was 11 min 6 s in June 2016 while exposure time for achieving therapeutic dose of 2 J/cm2 was 52 min 5 s in January 2017. The duration of exposure was found to be significantly longer in the winter months. LIMITATION: The limitation of the study is not determining ultraviolet B radiation and infrared exposure. Other limitation of this study is that the irradiance was measured only at 10 am. This data cannot be used to determine irradiance at different time points in the day as the patient may expose himself/herself to sunlight anytime depending on his/her convenience. CONCLUSIONS: The study demonstrates the mean exposure time required for a given therapeutic dose of ultraviolet A in different months. The wide variation in ultraviolet A irradiance in natural sunlight over the year in different months also suggests that exposure times for PUVAsol should be based on the season and geographical location at the site of therapy and not based on uniform guidelines.

Efficient UV Filter Solubilizers Prevent Recrystallization Favoring Accurate and Safe Sun Protection.

Sun protection is a global concern, and maximizing sunscreen stability and efficacy depends partially on the prevention of UV filters recrystallization. We aimed to study the efficacy of hydrophobic solubilizers in preventing the recrystallization of solid hydrophobic UV filters in predissolutions, sunscreen formulations, and during simulated human use. Recrystallization of UV filters induced by ultrasonication, temperature variation, or simulated human application was analyzed by different methods. Maximum solubility of UV filters in solubilizers was determined. Surprisingly, the best solubilizer was not necessarily the best solvent to prevent recrystallization, suggesting there are different forces controlling these phenomena. Hydrophobic solubilizers tend to perform better than ethanol in predissolutions, but the presence of other components in final products may change their performance. Results suggest that some UV filters tend to form liquid clusters, which may behave as crystals and affect the desired even distribution of UV filters on the skin. UV filters were also found to respond differently to Hansen Solubility Parameters. Scanning electron microscopy supports the fact that recrystallization upon sunscreen application is an issue to be tested during development. A timesaving method to predict recrystallization of UV filters in clear systems was developed and is presented as a tool to enhance the efficacy of sunscreens.

Probing the structure-function relationship of Mycobacterium leprae HSP18 under different UV radiations.

Ultraviolet radiation, an effective sterilizing source, rapidly kills the causative organism (Mycobacterium leprae) of leprosy. But, the reasons behind this quick death are not clearly understood. Also, the impact of UV radiation on the antigen(s) which is/are responsible for the survival of this pathogen is still unknown. Many reports have revealed that M. leprae secrets a major immunodominant antigen, namely HSP18, whose chaperone function plays an important role in the growth and survival of this pathogen under various environmental insults. However, the effect of UV radiation on its structure and chaperone function is still unclear. Therefore, we have taken a thorough attempt to understand these two aspects of HSP18 under different UV radiations (UVA/UVB/UVC; doses: 1-50 J/cm2). Our study revealed that its chaperone function is decreased significantly with increasing doses of various UV radiations. These different UV irradiations perturb only its tertiary structure and induce tryptophan and tyrosine photo-oxidation to N-formyl kynurenine, kynurenine and dityrosine. Such photo-oxidation promotes the subunit cross-linking within a HSP18 oligomer, lowers the surface hydrophobicity and thermostability of the protein. All these factors together damage/reduce the chaperone function of HSP18 which may be an important factor behind the rapid death of M. leprae under UV exposure.

Effects of air pollution on the skin: A review.

The increase in air pollution over the years has had major effects on the human skin. Various air pollutants such as ultraviolet radiation, polycyclic aromatic hydrocarbons, volatile organic compounds, oxides, particulate matter, ozone and cigarette smoke affect the skin as it is the outermost barrier. Air pollutants damage the skin by inducing oxidative stress. Although human skin acts as a biological shield against pro-oxidative chemicals and physical air pollutants, prolonged or repetitive exposure to high levels of these pollutants may have profound negative effects on the skin. Exposure to ultraviolet radiation has been associated with extrinsic skin aging and skin cancers. Cigarette smoke contributes to premature aging and an increase in the incidence of psoriasis, acne and skin cancers. It is also implicated in allergic skin conditions such as atopic dermatitis and eczema. Polyaromatic hydrocarbons are associated with extrinsic skin aging, pigmentation, cancers and acneiform eruptions. Volatile organic compounds have been associated with atopic dermatitis. Given the increasing levels of air pollution and its detrimental effects on the skin, it is advisable to use strategies to decrease air pollution.

The utility of dermoscopy in the diagnosis of evolving lesions of vitiligo.

BACKGROUND: Early lesions of vitiligo can be confused with various other causes of hypopigmentation and depigmentation. Few workers have utilized dermoscopy for the diagnosis of evolving lesions of vitiligo. AIM: To analyze the dermoscopic findings of evolving lesions in diagnosed cases of vitiligo and to correlate them histopathologically. METHODS: Dermoscopy of evolving lesions in 30 diagnosed cases of vitiligo was performed using both polarized light and ultraviolet light. RESULT: On polarized light examination, the pigmentary network was found to be reduced in 12 (40%) of 30 patients, absent in 9 (30%), and reversed in 6 (20%) patients; 2 patients (6.7%) showed perifollicular hyperpigmentation and 1 (3.3%) had perilesional hyperpigmentation. A diffuse white glow was demonstrable in 27 (90%) of 30 patients on ultraviolet light examination. Melanocytes were either reduced in number or absent in 12 (40%) of 30 patients on histopathology. CONCLUSION: Pigmentary network changes, and perifollicular and perilesional hyperpigmentation on polarized light examination, and a diffuse white glow on ultraviolet light examination were noted in evolving vitiligo lesions. Histopathological examination was comparatively less reliable. Dermoscopy appears to be better than routine histopathology in the diagnosis of evolving lesions of vitiligo and can obviate the need for a skin biopsy.

Discovery of low mucus adhesion surfaces.

Mucus secretion from the body is ubiquitous, and finding materials that resist mucus adhesion is a major technological challenge. Here, using a high throughput platform with photo-induced graft polymerization, we first rapidly synthesized, screened and tested a library of 55 different surfaces from six functional monomer classes to discover porcine intestinal low mucus adhesion surfaces using a 1h static mucus adsorption protocol. From this preliminary screen, two chemistries, a zwitterionic ([2-(acryloyloxy)ethyl] trimethylammonium chloride) and a multiple hydroxyl (N-[tris(hydroxymethyl)methyl]acrylamide) surface, exhibited significantly low mucus adhesion from a Langmuir-type isotherm when exposed to increasing concentrations of mucus for 24 h. Apolar or hydrophobic interactions were likely the dominant attractive forces during mucus binding since many polar or hydrophilic monomers reduced mucus adhesion. Hansen solubility parameters were used to illustrate the importance of monomer polarity and hydrogen bonding in reducing mucus adsorption. For a series of polyethylene glycol (PEG) monomers with changing molecular weight from 144 g mol⁻¹ to 1100 g mol⁻¹, we observed an excellent linear correlation (R²=0.998) between relative amount adsorbed and the distance from a water point in a specialized Hansen solubility parameter plot, emphasizing the role of surface-water interactions for PEG modified surfaces.

Photodermatoses in India.

Photodermatoses are a group of disorders resulting from abnormal cutaneous reactions to solar radiation. They include idiopathic photosensitive disorders, drug or chemical induced photosensitivity reactions, DNA repair-deficiency photodermatoses and photoaggravated dermatoses. The pathophysiology differs in these disorders but photoprotection is the most integral part of their management. Photoprotection includes wearing photoprotective clothing, applying broad spectrum sunscreens and avoiding photosensitizing drugs and chemicals.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Need for a well-balanced sunscreen to protect human skin from both Ultraviolet A and Ultraviolet B damage.

Skin exposure to sunlight can cause many adverse effects. It is now recognized that both Ultraviolet A (UVA) and UVB wavelengths are responsible for the detrimental effects of solar radiation on skin. With our increasing knowledge on the harmful effects of UVA, the need for effective, well-balanced photoprotection has become more crucial. Numerous clinical studies showed that well-balanced sunscreen, with a SPF/UVAPF ratio ≤ 3, provide the most effective protection against pigmentation (especially on dark skin), DNA damage, UV-induced skin immunosuppression and photodermatoses. The calculation of UVA protection required in Asia revealed its particular importance in India, and gives clear evidence that the SPF value alone is not sufficient to evaluate the efficacy of a sunscreen.

The development of efficient sunscreens.

Skin exposure to acute or repetitive ultraviolet light induces risks which are now well identified. An efficient photoprotection is thus required for both UVB and UVA radiation. In particular, increasing evidence of the detrimental effects of UVA on skin has led to the development of a new generation of sunscreens that provide effective protection throughout the whole UV radiation spectrum. Many new UV filters have been introduced in the last decade, particularly UVA filters, with improved efficacy and safety. Sunscreen filters must be carefully combined to achieve esthetically pleasing products offering photostable and well-balanced photoprotection.

Cutaneous solar ultraviolet exposure and clinical aspects of photodamage.

Solar ultraviolet (UV) radiation reaching the earth is a combination of UVB (290-320 nm) and UVA (320-400 nm) wavelengths. Since UVA is less energetic than UVB, UVB has long been thought to be the factor responsible for the damaging effects of solar radiation. But with modern tools such as in vitro models, it has been proven that UVA plays a major role. The objective of this review is to show how skin may be exposed to UV light and to highlight the clinical aspects of UV-induced skin damages with the respective contribution of UVB or UVA. Even if UVA is less energetic than UVB, it is more abundant and penetrates deeper into the skin, reaching as far as the dermis. Various factors also influence skin exposure to UV light: the latitude, season, and time of the day. Acute as well as chronic sun exposure induces short- and long-term clinical damages. Erythema and pigmentation are immediate responses of normal human skin exposed to UV radiation. The long-term effects are photoaging and photocarcinogenesis. In particular, UVA appears to play a major role in the deterioration of dermal structure leading to the photoaged appearance of the skin.

The effect of H1 and H2 receptor antagonists on melanogenesis.

BACKGROUND: Histamine was found to stimulate melanogenesis in cultured human melanocytes specifically mediated by histamine H 2 receptors via protein kinase A activation. Based on this finding, the effect of topically applied H 2 antagonist on UVB-irradiated Guinea pigs' skin was examined and found to be suppressive on the post-irradiation melanogenesis. AIMS: In this study, we tried to explore the role of topically applied H 1 and H 2 receptor antagonists, in inhibition of UVB-induced melanization. METHODS: The effect of topically applied H 1 and H 2 receptor antagonists in inhibition of melanization was done clinically and histochemically using Fontana Masson and DOPA reactions compared with placebo. RESULTS: The post-irradiation pigmentation was found to be brownish/black instead of the original light brown color. This color change occurred below the shaved orange-red fur suggesting a switch of melanogenesis from pheomelanin to eumelanin. The induced pigmentation was suppressed by topically applied H 2 antagonist while both H 1 antagonist and vehicle had no effect. The microscopic examination showed that the keratinocytes in the H 2 antagonist-treated areas contained few melanosomes while the nearby dendrites are full of them. CONCLUSION: H 2 antagonists' inhibition of UVB-induced pigmentation is not only due to suppression of melanization but also due to a specific action on melanosomes' transfer.