Melasma,a photoaging disorder

Melasma is a common hyperpigmentary disorder. The impact on the quality of life of affected individuals is well demonstrated, demanding new therapeutic strategies. However, the treatment of melasma remains highly challenging. Melasma is often considered as the main consequence of female hormone stimulation on a predisposed genetic background. Although these two factors do contribute to this acquired pigmentary disorder, the last decade has revealed several other key players and brought new pieces to the complex puzzle of the pathophysiology of melasma. Here, we summarize the latest evidence on the pathophysiology of melasma, and we suggest that melasma might be a photoaging skin disorder affecting genetically predisposed individuals. Such data must be taken into consideration by clinicians as they could have a profound impact on the treatment and the prevention of melasma.     

Recent progress in melasma pathogenesis

Melasma is a common skin pigmentation condition. Given therapeutic difficulty as one of the biggest concerns, understanding of the etiology and pathogenesis of melasma becomes essential. UV irradiation, female sex hormones, and inflammatory processes are addressed as triggering factors with genetic predisposition. The mechanism of UV‐induced melanogenesis has been extensively investigated as a model system to study melasma pathogenesis. Hitherto, treatment modalities for melasma are similar to other hyperpigmentation disorders. However, individual triggering factors induce a separate pigmentation disease, whose pathogenic mechanisms and clinical phenotypes are different from the ones encountered in melasma. Fortunately, there have been ongoing updates on melasma pathogenesis with regard to major triggering factors. Presence of certain factors working independently of UV exposure and role of dermal factors and microRNAs are being identified as novel discoveries about melasma pathogenesis. In this review, the melasma pathogenesis is reviewed in association with updated and new findings.     

In vivo multiphoton microscopy of melasma

Melasma is a skin disorder characterized by hyperpigmented patches due to increased melanin production and deposition. In this pilot study, we evaluate the potential of multiphoton microscopy (MPM) to characterize non‐invasively the melanin content, location, and distribution in melasma and assess the elastosis severity. We employed a clinical MPM tomograph to image in vivo morphological features in melasma lesions and adjacent normal skin in 12 patients. We imaged dermal melanophages in most dermal melasma lesions and occasionally in epidermal melasma. The melanin volume fraction values measured in epidermal melasma (14% ± 4%) were significantly higher (p < 0.05) than the values measured in perilesional skin (11% ± 3%). The basal keratinocytes of melasma and perilesions showed different melanin distribution. Elastosis was predominantly more severe in lesions than in perilesions and was associated with changes in melanin distribution of the basal keratinocytes. These results demonstrate that MPM may be a non‐invasive imaging tool for characterizing melasma.     

Occupational skin diseases caused by solar radiation

UV radiation is present in sunlight and can be emitted from numerous artificial sources. Outdoor workers are exposed to sunlight in a wide variety of occupations like sailors, fishers, construction workers, farmers, and other. Presented are the skin diseases caused by sunlight exposure. They may be of little medical importance such as stigmata or create problems like photoaging, skin carcinoma, melanoma, phototoxic and photoallergic reactions. Shown are briefly data on skin cancer in the Rijeka region in outdoor occupations, the legislation and necessity for prevention. Psoriatic patients need particular caution because they are exposed to UVR, tars, and immunosuppressive drugs during the treatment.     

Polar lipids in cosmetics: recent trends in extraction,separation, analysis and main applications

Demand for active, natural, safe and biomimetic (similar to human molecules) plantderived cosmetic ingredients is always greater because consumers are increasingly suspicious of the potential toxicity of current ingredients. In this context, interest has increased for polar lipids like ceramides, sphingolipids or glycolipids that share structural properties with the skin lipids. In the same manner, processes to obtain such lipids should be driven by the principles of green chemistry and sustainable development. The identified needs are biodegradability, biocompatibility, efficiency, quality and profitability. In this research for new and novel natural or ‘green’ compounds, the development of bioactive lipids thanks to ecofriendly processes has obviously intensified, especially for cosmetic and agro-food industries. This paper reviews extraction methods for polar lipids (glycolipids and phospholipids), especially ecoprocesses (supercritical fluid extraction, microwaves, sonication, enzyme extraction…), and promising chromatographic methods like countercurrent chromatography, supercritical fluid chromatography or high performance chromatography coupled to mass spectrometry Interests of polar lipids for cosmetic industries are exemplified to show their broad applications mostly relying on their amphiphilic properties allowing them to play functional roles (liposome or micelle structures for example) or physiological roles (skin barrier function or anti-ageing effect).     

Role of flavonoids in controlling the phototoxicity of Hypericum perforatum extracts.

Hypericum perforatum extracts are used mainly as oral antidepressants. Depending on source the extracts contain various amounts of phenylpropanes, flavonol derivates, biflavones, proathocyanidines, xanthones, phloroglucinoles, some amino acids, naphtodianthrones (hypericines) and essential oil constituents. The therapeutic use of Hypericum perforatum extracts however is limited by their phototoxic potential. It was the aim of the present study to investigate the phototoxic potential of 3 Hypericum perforatum extracts from different sources as well as some of its main constituents. In order to systematically study the phototoxic potential we established a modified neutral red assay utilizing an immortalized human keratinocyte cell line (HaCaT cells) as substrate and UVA irradiation. This modified neutral red assay was found to be a simple and reliable method for detecting phototoxic effects of reference agents and plant extracts. The validity of this method was demonstrated with known phototoxic compounds like chloropromazine and psoralenes like 5-MOP. Hypericum perforatum extracts demonstrated cytotoxicity and photocytotoxicity in a dose and UVA-dose dependent manner. Hypericine itself also evoked severe phototoxic effects and was thus identified as the main phototoxic constituent. Among the tested flavonoids quercitrin was found to be cytotoxic, while rutin unexpectedly demonstrated phototoxicity whereas quercitrin was effective to control the phototoxic activity of Hypericum perforatum extracts.     

Evaluation of chemically-induced phototoxicity to aquatic organism using Paramecium as a model

Phototoxicity evaluation using Paramecium aurelia as a model revealed that 4 out of 21 pesticides produced lethal toxicity to cells. Four commonly used synthetic dyes (bromophenol blue, rose bengal, benzanthrone and methylene blue) also exhibited toxicity. Well known phototoxic agents like hematoporphyrin, riboflavin, and anthracene produced positive phototoxic response. Psoralen, a DNA cross-linking agent, also produced phototoxicity to the cells. The results clearly demonstrate that the synergistic action of chemical agents and sunlight produce lethal effects to aquatic organism.     

Selection for skin color among the Japanese

A reflectance spectrophotometer was used to record the skin color on the inner side of the upper arm on a series of 421 Japanese students of both sexes aged 15 through 19. All geographic regions in the country, and the upper, middle and lower socioeconomic classes were represented. It was found that, as among most peoples previously studied, males are darker than females. Boys from northern Japan are, on average, a bit lighter than are those from the southwest, but there are no geographically based differences among the girls. In both sexes and all areas, the mean reflectance values of the upper class group are higher than in the middle and lower class groups, but the difference is most pronounced among the males. It is therefore concluded that social selection for light skin color has had some genetic effect.     

Phototoxic and photoallergic skin reactions

Indirect action of sun together with different exogenous agents (systemic medications and topically applied compounds) sometimes may result in phototoxicic and photoallergic reactions. Drug-induced photosensitivity reactions refer to the development of cutaneous disease as a result of the combined effects of a drug and light (mostly spectrum within the UVA and visible light range or UVB range). The aim of the review was to show the prominent features of phototoxic and photoallergic reactions, which occur in sun-exposed areas, including face, neck, hands and forearms. Phototoxic reactions are significantly more common than photoallergic reactions and mostly resemble to exaggerated sunburn. Photoallergic reactions appear only in a minority of individuals and resemble allergic contact dermatitis on sun-exposed areas, although sometimes may extend into covered areas. Generally, the physical examination and a positive patient's history of photosensitivity reactions on substances are of great importance for the diagnostics. The treatment of these reactions includes identification and avoidance of offending agent and application of anti-inflammatory dressings, ointments and corticosteroids.     

Immediate pigment darkening: its evolutionary roles may include protection against folate photosensitization

The evolution of dark human skin colors in tropical areas is possibly related to photoprotection of folates. However, natural folates absorb mainly UVB radiation, and too little UVB can penetrate down to folates in dermal vessels to cause serious damage. However, endogenous photosensitizers, like riboflavin and uroporphyrin, absorbing UVA and visible light, can cause photosensitization of folates. Immediate pigment darkening (IPD), generated by UVA, has an absorption spectrum covering those of the endogenous photosensitizers. IPD is most prominent for darker skin types, which were typical for populations living under tropical solar fluences. We here propose that the biological role of IPD is protection of folates against photodegradation, which would be of large evolutionary importance for early hominids.     

Efficacy of hydroquinone in the treatment of cutaneous hyperpigmentation in hairless descendants of Mexican hairless dogs (Xoloitzcuintli)

The skin of adult hairless dogs is clinically nonpigmented, clinically lightly pigmented, or clinically hyperpigmented (spotty pigmented). The pigment noted clinically is attributable to melanin granules in the epidermis. Spotty pigmentation in the skin of adult hairless dogs was treated by administration of the depigmenting agent (3% hydroquinone, HQ) for 1 month. Depigmenting effects were examined by use of three methods: skin color, dihydroxyphenylalanine (DOPA)-positive melanocyte count, and histologic evaluation. The treated skin of hairless dogs began to become depigmented after application of HQ for 1 week. After 1 month of treatment with HQ, depigmentation spread over a quarter of the body. The number of DOPA-positive melanocytes in the HQ-treated sites decreased to less than approximately a fifth of that before treatment. In HQ-treated skin, histologic staining by use of Fontana-Masson's (FM) method revealed complete absence of melanin pigment. These results suggested that hairless dogs should be a useful animal model for investigating the effects and cutaneous toxicity of depigmenting agents.     

Drug-induced photosensitivity: phototoxic and photoallergic reactions--a few molecular aspects

Drug-induced photosensitivity involves mainly phototoxic and photoallergic reactions. The main features of phototoxic and photoallergic reactions are presented and some molecular aspects involved in the mechanisms leading to an adverse skin response are illustrated with examples.     

Size reduction associated with brachymesophalangia-5: a possible selective advantage

The skin reflectance characteristics of a group of Quechua Indians have been described with an emphasis upon the effects of varying degrees of hybridization, sex and age. This group of Peruvian Indians occupied a reflectance range common to that of all other reported groups of South American Indians. Miscegenation with European Whites had a statistically significant although small influence upon skin color. In general males were consistently darker than females on the three body sites measured. A significant darkening on unexposed body areas occurred in both sexes during early adolescence which may have been caused by the high activity level of the pituitary gland at that stage of the growth cycle.     

Chemical and instrumental approaches to treat hyperpigmentation

Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. Depigmenting compounds should act selectively on hyperactivated melanocytes, without short- or long-term side-effects, and induce a permanent removal of undesired pigment. Since 1961 hydroquinone, a tyrosinase inhibitor, has been introduced and its therapeutic efficacy demonstrated, and other whitening agents specifically acting on tyrosinase by different mechanisms have been proposed. Compounds with depigmenting activity are now numerous and the classification of molecules, based on their mechanism of action, has become difficult. Systematic studies to assess both the efficacy and the safety of such molecules are necessary. Moreover, the evidence that bleaching compounds are fairly ineffective on dermal accumulation of melanin has prompted investigations on the effectiveness of physical therapies, such as lasers. This review which describes the different approaches to obtain depigmentation, suggests a classification of whitening molecules on the basis of the mechanism by which they interfere with melanogenesis, and confirms the necessity to apply standardized protocols to evaluate depigmenting treatments.     

Geographic distribution of human skin colour: A selective compromise between natural selection and sexual selection?

Modern humans have been shaped by the cumulative action of natural selection, non-adaptive random change, and sexual selection. The last of these is not universal and has prevailed in one of two circumstances: (1) A surplus of females due to high male mortality, combined with ecological constraints on female participation in food procurement which discourage males from taking second wives; (2) A surplus of single males due to generalized polygyny with relatively low male mortality. These circumstances are most likely to occur in (1) Arctic tundra environments, specifically the vast expanse of tundra covering most of Europe up to 10,000 B.P., and in (2) regions dominated by generalized polygyny, notably sub-Saharan Africa. Sexual selection often acts on existing sex differences, including perhaps sexual dimorphism in human skin colour. Whereas women are universally fairer in complexion, men are browner and ruddier; parallel to this, most human societies see lighter skin as more feminine and darker skin as more masculine. Hence, sexual selection should favour lighter pigmented women when a surplus of single females must compete for a mate. Since skin colour is only mildly sex-linked, both sexes would lighten in pigmentation within the population in question. Similarly, when a surplus of single males must compete for a mate, both sexes would darken. Geographic variation in human skin colour may thus represent a selective compromise between two counterbalancing forces: natural selection, as determined by latitudinal variation in sunlight; and sexual selection, as determined by variations in the following: male mortality rates, incidence of polygyny, and ecological constraints on female participation in food procurement.     

我院2010年度药物不良反应分析

目的分析药物不良反应(ADR)发生的特点与规律,促进临床合理用药。方法回顾性分析2010年1~12月我院上报的401份ADR报告,按患者年龄、性别、给药途径、引起ADR的药品种类、涉及器官或系统以及临床表现等进行统计、分析。结果静脉给药较其他给药途径更易发生ADR(336例,占83.89%);抗感染药物引发ADR的比例最高(159例,占39.65%),其次为营养药、消化系统药物及抗肿瘤药物;头孢菌素类药物是引发ADR的主要抗菌药物(15种,28.85%),其次为青霉素类(10种,19.23%)。ADR主要累及皮肤及附件损害为主,其次涉及到消化系统以及神经系统损害。结论临床科室应重视ADR监测,减少ADR的发生,提高合理用药水平。