Procyanidin B-3, isolated from barley and identified as a hair-growth stimulant,has the potential to counteract inhibitory regulation by TGF-beta1

With the aim of identifying natural products, which possess hair-growing activity, we examined more than 1000 plant extracts with respect to their growth-promoting effects on hair epithelial cells. We discovered intensive growth-promoting activity, about 140% relative to controls, in barley extract. Our strategy for identifying active compounds in barley extract involved subjecting it to column chromatography using HP-20 resin columns, an LH-20 resin column, and preparative high-performance liquid chromatography (HPLC) using an ODS column. The 60% (v/v) aqueous methanol eluted fraction from the HP-20 column and the 75% (v/v) aqueous methanol eluted fraction from the subsequent LH-20 column showed high hair-growing activity in vivo. We isolated two major substances from the LH-20 active fraction using preparative HPLC. By means of mass spectrometry, 1H-NMR, and 13C-NMR analyses, one substance was revealed to be procyanidin B-3 and the other substance was identified as (+)-catechin. Purified procyanidin B-3 showed high hair-growing activity in the form of in vitro hair epithelial cell growth-promoting activity and in vivo anagen-inducing activity; however (+)-catechin showed no hair-growing activity. For the purpose of examining the hair-growing mechanisms of procyanidin B-3, we examined its relationship to the TGF-beta signal pathway, which is known to be a regulator of catagen induction. Addition of TGF-beta1 to hair epithelial cell cultures dose-dependently decreased the cell growth, and addition of procyanidin B-3 to the culture neutralized the growth-inhibiting effect of TGF-beta1. From these results, it is concluded that procyanidin B-3 can directly promote hair epithelial cell growth in vitro, has the potential to counteract the growth-inhibiting effect caused by TGF-beta1 in vitro, and has potential to stimulate anagen induction in vivo.     

分子靶向抗肿瘤药物皮肤不良反应研究进展

近年来靶向抗肿瘤药物的使用在恶性肿瘤治疗中逐渐广泛,显著提高了患者生存率,但其引起的皮肤不良反应十分常见.根据作用靶点的不同对靶向药物不良反应进行分类分析,可找出其中的共性与个性,为皮肤科及肿瘤科医生提供诊疗的新思路.本文将分别从细胞膜相关抑制剂、胞内信号通路抑制剂及免疫检测点抑制剂三个方面综述临床上较为常见的靶向药物...     

UV transmission and UV protection factor (UPF) measured on split skin following exposure to UVB radiation — correlation with the minimal erythema dose (MED)

In this study the ultraviolet (UV) transmission of split skin exposed to UVB radiation and of non-exposed skin was compared in the 280-390 nm wavelength range and quantified. In addition, the correlation between the increase in the minimal erythema dose (MED) associated with a defined exposure to UVB and the ultraviolet protection factor (UPF) calculated from the transmission data was investigated. The study population consisted of 12 patients. Two pieces of split skin of the same thickness (0.3 mm) were taken from the right thigh of each patient. One specimen was removed from an area of non-exposed healthy skin and the other from an area which had been exposed to UVB radiation for a period of 12 days in which the initial dose of 1/3 MED was raised by 1/3 MED every 4 days. The split skin specimens were stretched over a special frame; subsequently, the UV transmission was determined with a spectrophotometer. The mean values obtained for UV transmission were all significantly below the initial data for non-exposed split skin. In the UV range of 280--390 nm, the transmission measured in the exposed specimens was 49.1% of the value measured in the non-exposed split skin (P<0.05). The corresponding values for the UVA range (315--390 nm) and the UVB range (280--315 nm) were 50.1% and 29.5%, respectively (P<0.05), based on the initial transmission data obtained from non-exposed skin. The clinical determination of MED after 12 days of exposure to UVB yielded mean values that were 3.2 times the initial values. Moreover, the mean UPFs calculated from the transmission data measured at the end of the 12-day exposure period were also about three times the initial values. The present study has thus established a significant correlation between the clinical MED values and the UPFs calculated from the transmission data measured following exposure to UVB.     

胎鼠真皮成纤维细胞皮内注射对UV诱导小鼠皮肤光老化的改善作用

目的: 探索体外培养胎鼠真皮成纤维细胞(fibroblasts,FBs)皮内注射对小鼠背部光老化皮肤的改善作用.方法: 分离培养10只第18.5天(E18.5)BALB/c胎鼠皮肤,体外培养FBs两天;用CM-Dil荧光染料进行活细胞标记,以示FBs注射后在体内存活情况.取BALB/c雄性小鼠20只,随机分为:未处理组...     

Photosensitivity of murine skin greatly depends on the genetic background: clinically relevant dose as a new measure to replace minimal erythema dose in mouse studies

Artificial UV irradiation of murine skin is a frequently used method for testing photosensitivity, study carcinogenesis and photoprotective effects of different compounds. However, doses of UV radiation and mouse strains used in experiments vary greatly. The genetic background of mice may influence the photosensitivity as melanin content, pigmentation and hair cycle parameters are dissimilar. Doses of UV are often expressed in relation to the minimal erythema dose (MED) that was not necessarily determined for the given strain. We set out to standardize the method of measuring photosensitivity in three commonly used mouse strains, C57BL/6N, Balb/c and SKH‐1. We found that MED may not be determined for some strains as erythema development in mice with diverse genotypes differs greatly. We measured the oedema response in vivo and ex vivo by using OCT. Given the strain‐specific variability of erythema, we introduced Clinically Relevant Dose (CRD) as a new term to replace MED in experiments, to describe the lowest dose that triggers a perceptible skin reaction in mice. Not only the CRD but the proportion of erythema and oedema were different in strains examined. C57BL/6N mice display skin reactions at the lowest UVB dose, while SKH‐1 hairless mice show changes, mostly oedema, after higher doses of UVB. The cellular composition and skin thickness were examined by histopathology. IL‐1beta and IL‐6 levels in skin correlated with the increasing doses of UVB. Despite the variations in the degree of erythema and oedema, no major differences in cytokine expressions were seen among various strains of mice.     

Cultured skin fibroblasts derived from three patients with disseminated superficial actinic porokeratosis (DSAP) are hypersensitive to the lethal effects of X-radiation but not to those of ultraviolet (UV) light

Abstract Disseminated superficial actinic porokeratosis (DSAP), skin lesions of which are known to be induced by ultraviolet (UV) light, does not develop into skin cancer as frequently as other types of porokeratosis (PK) To establish the cellular basis of this characteristic of DSAP. we examined the colony-forming ability of UVC light- or X-ray-irradiated cultured fibroblasts derived from DSAP patients' skin. Sensitivity to the lethal effects of UV light was not significantly different between 3 DSAP and 5 control cell strains. In contrast, DSAP cell strains were significantly hypersensitive to the lethal effects of X-radiation, although the sensitivity was less than that of cell strains from other types of PK patients. The results indicate that the actinic character of DSAP is not reflected in the cellular response to the lethal effects of UV light, but suggest that DSAP shares X-ray sensitivity, which is probably associated with the cancer-prone nature of PK.     

Occupational exposure to non‐artificial UV‐light and non‐melanocytic skin cancer – a systematic review concerning a new occupational disease

Background: Although UV exposure is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), a systematic review analyzing the risk of occupational UV exposure is missing. Methods: Based on a systematic literature search in PubMed (until 05/2009) supplemented by hand search, the association between occupational UV exposure and SCC and BCC was analyzed. Literature search and data abstraction was done independently by 2 reviewers. The association between occupational UV exposure and cancer risk is presented as odds ratios (OR). Results: We identified 25 relevant epidemiologic studies (5 cohort studies, 17 case‐control studies, 3 cross‐sectional studies). 12 studies described a positive association between occupational UV exposure and risk of SCC with OR > 3 in 6 studies and OR 1.5–2.0 in another 6 studies. 3 studies did not find a relevant association (OR: 1.0–1.4). A significant positive association between occupational UV exposure and BCC was reported in 5 studies; 11 studies did not find a significant association. Conclusions: The association between occupational UV exposure and SCC is well and consistently documented epidemiologically (approximately 2‐fold increased risk), so that the criteria for a new occupational disease are fulfilled. The association with BCC is unclear due to significant methodological limitations in the published studies.     

Age-dependent response of energy metabolism of human skin to UVA exposure: an in vivo study by 31P nuclear magnetic resonance spectroscopy

Purpose The aim of our study was to evaluate the in vivo energy metabolism of human skin as a function of age, in conditions of rest and after a mild stress caused by a suberythemal UVA irradiation. Methods The kinetics of UVA-induced modifications in high-energy phosphorylated metabolites of young and old skins were non-invasively monitored over a period of 24 h using ³¹P nuclear magnetic resonance spectroscopy. In vivo³¹P spectra were obtained on the ventral aspect of the wrist, using a NMR Imaging Spectrometer equipped with a double-tuned surface coil. Concentrations of phosphocreatine, inorganic phospate, adenosine tri-phosphate, phosphomono and phosphodiesters were calculated from the spectra and results were expressed as relative concentrations. A total of 20 subjects were enrolled in this study (n = 10 for the age group below 25 years and n = 10 for the age group above 55 years). A second experiment was then performed on 10 old subjects (mean age 60) who were treated on one wrist, twice a day for one month prior to UVA irradiation, with a product that contained active ingredients to restore barrier function and modulate the inflammatory response, the other wrist being an untreated control. Results Baseline levels of phosphorylated metabolites were similar in young and old skins. A suberythemal dose of UVA (6 J.cm⁻²) led to a significant decrease in the PCr/Pi ratio (index of energy status) and a significant increase in the PME/PDE ratio (index of cellular turnover rate of lipid-related metabolites) within 1 h. The observed variations were transient and the recovery was complete at T + 24 h post-UVA, although recovery was significantly slower in the older group. The disturbances were significantly reduced after treatment of the older skin with a formula that restored barrier function of the stratum corneum and modulated the inflammatory response. Conclusion (i) baseline levels of energy metabolites in skin do not seem to vary with age; (ii) low dose UVA irradiation induces a rapid response in the energy metabolism of the skin; (iii) the kinetics of the response and recovery after an aggression by UVA suggest that older skin has significantly less energy rebound after a stress situation than younger skin; (iv) the energy reserve in older skin can be protected efficiently against UVA-induced stress by restoring barrier function and modulating the inflammatory response.