Cutaneous vessel features of sensitive skin and its underlying functions.

BACKGROUND: Following the sufficient studies of the effects of skin barrier impairment and heightened neural reaction on sensitive skin (SS), many scholars have paid great attention to the roles of superficial microvasculature in SS. METHODS: By questionnaire survey, lactic acid sting test, and capsaicin test, eligible subjects were classified as normal skin, only lactic acid sting test positive (LASTP), only capsaicin test positive (CATP), and both positive (both LASTP and CATP). D-OCT was used to photograph images for evaluating the cutaneous vessels features each group. RESULTS: Totally 137 subjects completed the study. Compared with LASTN group, the vascular vessels were closer to epidermis in LASTP group. Mesh and branching vessels were more popular in SS than normal skin. High blood vessel density was more prevalent in SS, while low density frequently presented in normal skin. The vascular depth had a closely negative correlation with face flushing and SSS, and vascular shapes had a good positive correlation with face flushing and SSB. CONCLUSIONS: Our study indicates that there is a significant difference in vascular depth, shape, and density between SS and normal skin which is valuable to explore SS pathologic mechanism and to further investigate cutaneous microvasculature functions in SS.

Revisit the 21-day cumulative irritation test - statistical considerations.

The 21-day cumulative irritation test is widely used for evaluating the irritation potential of topical skin-care products. This test consists of clinician's assessment of skin reaction of the patch sites and a classification system to categorize the test product's irritation potential. A new classification system is proposed which enables us to control the estimation error and provides a statistical confidence with regard to the repeatability of the classification.

Elicitation threshold of cobalt chloride: analysis of patch test dose-response studies.

BACKGROUND: Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. OBJECTIVE: To identify the dermatitis elicitation threshold levels in cobalt-allergic individuals. MATERIALS AND METHODS: Published patch test dose-response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose-response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED(10)) of a population was calculated with Fieller's method. RESULTS: On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm(2), corresponding to 30.8-259 ppm. CONCLUSIONS: Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy.

Safety and reliability of the drug tolerance test: our experience in 739 patients.

BACKGROUND: Drug tolerance tests (DTTs) are commonly used to find a safe therapeutic alternative for patients with previous type B adverse drug reactions (ADRs), but few studies on safety and reliability are available. METHODS: We retrospectively studied 739 subjects with previous ADRs who underwent DTTs; 12 months after the test, use of the tested drug(s) and occurrence of ADRs were investigated in 260 of them. RESULTS: ADRs to antibiotics and nonsteroidal anti-inflammatory drugs were the main reasons for which DTTs were requested. 925 DTTs were performed in the 739 patients, with 97 ADRs. Twelve months after the test, 125/260 patients interviewed had used the tested drug(s): 118 of them experienced no ADR, 4 experienced 'true' ADRs, and 3 reported predictable/unclear reactions. CONCLUSION: Our data show that DTTs are safe and reliable at 1 year, but patients and general practitioners do not trust them. It is strongly advisable to have better information on methods, benefits, risks and reliability of DTTs.

Coenzyme Q10 nanostructured lipid carriers as an inducer of the skin fibroblast cell and its irritability test in a mice model.

Background Coenzyme Q10 is a fat-soluble antioxidant that can help to prevent collagen and elastin damage and avoid wrinkles. Coenzyme Q10 has several disadvantages to be formulated in topical dosage forms, such as low water solubility and large molecular weight. These make coenzyme Q10 retained in the stratum corneum and cause low skin penetration, so proper formulation is required to get products that can penetrate the skin layer. A nanostructured lipid carrier (NLC) consists of a matrix of solid lipids and liquid lipids in a certain amount with nanoparticle size; it may help increase the penetration of active ingredients. Methods For the antiaging activity test, mice were grouped into four treatment groups and killed on the 14th day; then the back of the skin was stained with Masson trichrome staining. For the irritation test, the mice were grouped into three groups and killed after 24 h; then the back of the mice was stained with hematoxylin-eosin staining. Results The number of fibroblasts in mice with NLC coenzyme Q10 is highest from all test groups. The irritation test results after 24 h of application preparation showed that NLC coenzyme Q10 did not irritate the skin of the back of male mice. Conclusions One percent coenzyme Q10 loaded in NLC induced the number of fibroblast cells in the mice model and showed no irritability effect in histopathology preparations.

In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp.

Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities. However, until now, their antibacterial activity against Propionibacterium sp. has not been reported. To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay. Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria. The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively. In addition, the killing curve analysis showed that magnolol and honokiol killed P. acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml. The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT. In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent. In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes in THP-1 cells indicating the anti-inflammatory effects of them. When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test. Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.

In vivo investigation, in mice and in man, into the irritation potential of novel amphiphilogels being studied as transdermal drug carriers.

Amphiphilogels, gels that consist solely of non-ionic surfactants, are being developed as dermal/transdermal drug delivery vehicles in our laboratories. The irritation potential of two amphiphilogels was investigated on shaved mouse skin, in vivo, and compared to those of Aqueous Cream BP (a moisturiser) and 5% sodium lauryl sulphate (SLS) solution (a known irritant). The skin irritation potential of one of these gels was then investigated in human, using Aqueous Cream BP as a negative control. Skin irritation (following daily application of gels and of controls for 5 days) was assessed by laser Doppler velocimetry, a visual erythema scoring method, and histological evaluations of excised mice skin. We found that the amphiphilogels caused no significant increase in blood flow and in epidermal irritation. In contrast, the SLS solution caused significant perturbation to mouse skin. From this study we conclude that these amphiphilogels may be used as dermal/transdermal drug delivery vehicles.

Skin permeation enhancement effect and skin irritation of saturated fatty alcohols.

Though the skin permeation enhancement effect of chemical penetration enhancers has been studied extensively, their skin irritation potential has not been adequately investigated. The objective of this study was to evaluate the skin permeation enhancement effect and skin irritation of saturated fatty alcohols using melatonin as a model compound. A saturated solution of melatonin in a mixture of water and ethanol (40:60) containing 5% w/v of saturated fatty alcohol was used in the skin permeation studies using Franz diffusion cells. For skin irritation studies, 230 microl of fatty alcohol solution was applied on the dorsal surface of the hairless rats using Hill top chamber. The skin irritation was evaluated by visual scoring method and bioengineering methods such as measurement of transepidermal water loss (TEWL) and skin blood flow. The flux of melatonin across hairless rat skin was found to be dependent on the carbon chain length of the fatty alcohols, with decanol showing the maximum permeation of melatonin. All fatty alcohols increased the TEWL and skin blood flow significantly compared with the vehicle. The fatty alcohols (decanol, undecanol and lauryl alcohol), which showed greater permeation of melatonin, also produced greater TEWL, skin blood flow and erythema. Tridecanol and myristyl alcohol showed lower permeation enhancement effect but caused greater skin irritation. Octanol and nonanol may be the most useful enhancers for the transdermal delivery of melatonin considering their lower skin irritation and a reasonably good permeation enhancement effect. However, further studies are needed to ascertain their safety as skin penetration enhancers. Skin permeation and skin irritation in experimental animals such as rats are generally higher compared with human skin. Further studies in human volunteers using fatty alcohols at the concentrations of 5% or lower may provide useful information on the utility of these fatty alcohols as permeation enhancers.

Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin.

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers.

[Analysis on skin allergy of rural residents in Anqing area].

To investigate the allergy reaction of rural residents against 12 categories sensibiligen, 9,232 sensibiligen peasants from rural areas of Anqing were observed by 12 categories sensibiligen in skin(methods: point thron). If the diameter of papule erygthema was bigger than that of histamines of control, the reaction was considered to be positive. All cata was analyzed by sas software. The results showed that the allergy reaction degrees were different among the groups with different genders and ages. Family susceptibility was noticed.

Skin irritation: prevalence, variability, and regulatory classification of existing in vivo data from industrial chemicals.

In vivo rabbit data for skin irritation registered in the European New Chemicals Database (NCD) and an ECETOC Database were evaluated to characterise the distribution of irritation potential among chemicals and to assess the variability of the animal test. These databases could be used to determine experimental and rudimentarily within-laboratory variability, but not between-laboratory variability. Our evaluation suggests that experimental variability is small. Using two classification systems--the system currently used in Europe and the Globally Harmonised System (GHS)--the prevalence of skin irritation data obtained from NCD was analysed. This analysis revealed that out of 3121 chemicals tested, less than 10% showed an irritation potential in rabbits which would require an appropriate hazard label and 64% did not cause any irritation. Furthermore, it appears that in practical use the European classification system introduces bias towards overclassification. Based on these findings, we conclude, that the classification systems should be refined taking prevalence into account. Additionally, prevalence should be incorporated into the design and analysis of validation studies for in vitro test methods and in the definition of testing strategies.

Reconstructed skin kits: reproducibility of cutaneous irritancy testing.

The aim of this study was to determine the reproducibility of data obtained from in vitro irritation testing using three industrial reconstructed human epidermis models, EpiDerm, Episkin and SkinEthic, and one in-house model developed at Wella/Cosmital. A common protocol was established based on the measurement of cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and of extracellular release of proinflammatory mediators and cytosolic enzymes after a range of exposure times to sodium lauryl sulfate (SLS). This time course protocol was applied to 6 different batches of each skin model using triplicate tissue cultures per test condition. The parameters analyzed for intra- and inter-batch reproducibility were the cell viability determined as MTT reduction capacity and the ET-50 values in the 6 batches, as well as the release of the cytokine IL-1alpha and of the cellular enzymes LDH and GOT in 3 batches only. The MTT viability results showed that EpiDerm was the most resistant to the SLS treatment and at the same time the most reproducible model, SkinEthic was the most sensitive to SLS and the least reproducible, and Episkin and the Cosmital model were intermediate. Measurements of IL-1alpha release showed a relatively high intra- and inter-batch variability in all the skin models. It was not possible to detect the extracellular release of the enzymes LDH and GOT in the Episkin assay medium. With the 3 other models, the release of LDH and GOT varied in about the same range as that of IL-1alpha. For all the parameters in this study, the inter-batch variability was generally greater than the intra-batch variability. A possible reduction in the number of batches and replicates for future applications in routine irritancy testing is discussed on the basis of the results obtained using 6 batches in triplicate.