Evaluation of the anti-wrinkle effect of a lipophilic pro-vitamin C derivative, tetra-isopalmitoyl ascorbic acid.

BACKGROUND: Tetra-isopalmitoyl ascorbic acid (VC-IP), an oil-soluble vitamin C derivative, is known to be effective for treating photoaging skin caused by oxidative stress. In addition, it is known that morphological changes of the skin occur on the face with aging, and the main cause has been reported to be photoaging. AIMS: There have not been any published reports that examined the clinical effects of vitamin C derivatives on periorbital wrinkles. The purpose of this study was to characterize the potential anti-wrinkle effect of VC-IP. METHODS: A double-blind, randomized, placebo-controlled, split face clinical trial was performed on 3 groups of 23 female subjects each who used 1%, 2%, or 3% VC-IP creams versus a placebo cream to treat their facial wrinkles. VC-IP cream was applied on the periorbital area on one side of the face of each subject twice a day for 8 weeks and a placebo cream was applied on the other side. Anti-wrinkle effects were evaluated by visual wrinkle grading and topographic assessments. RESULTS: Periorbital wrinkles treated with VC-IP twice a day for 8 weeks showed marked or moderate improvements according to visual observations and grading of photographs. Moreover, topographic assessments confirmed the improving effects of VC-IP, and more interestingly, the appearance of those effects differed depending on the VC-IP concentration. In addition, sufficient improvement was observed in parameters reported to be associated with dermal structure at lower concentrations of VC-IP. CONCLUSIONS: These results indicate that topical application of VC-IP cream reduces periorbital wrinkles caused by skin aging.

SkinEthic™ HCE Eye Irritation Test: Similar performance demonstrated after long distance shipment and extended storage conditions.

Assessment of ocular irritation risk is an international regulatory requirement in the safety evaluation of products. In response to this need, L'Oréal developed the SkinEthic™ Human Corneal Epithelium (HCE) Eye Irritation Test (EIT) that has been included in OECD Test Guideline 492. SkinEthic™ HCE EIT is able to correctly and reliably identify chemicals not requiring classification versus labelling for eye irritation or serious eye damage according to UN GHS. In an effort to promote its global use, the performance of the method was evaluated after long-distance shipment and compared to European shipment conditions. Results obtained by Cosmos Technical Center (Japan) after extended tissues transit were compared to results obtained in L'Oréal (France). Thirty-nine out of 40 blinded chemicals, representing different functional chemical classes, were consistently classified in both laboratories. The SkinEthic™ HCE EIT test method was also evaluated for its performance after extended storage of the tissues. The performance was in agreement with the values reported in OECD TG 492, with an overall accuracy of 87.1% (based on 119 chemicals), sensitivity of 95.5% and specificity of 73.5%. The reliability and relevance of SkinEthic™ HCE EIT test method after long-distance shipment and extended storage remain in agreement with regulatory validation criteria.

Ethyl 2,4-dicarboethoxy pantothenate, a derivative of pantothenic acid, prevents cellular damage initiated by environmental pollutants through Nrf2 activation.

BACKGROUND: Recently, environmental pollutants have become a concern not only for respiratory organs but also for skin-related human health, because skin is localized at the border between the human body and the external environment and is easily influenced by environmental pollutants. OBJECTIVE: Here, we investigated the effects of a novel pantothenic acid (PA) derivative, ethyl 2,4-dicarboethoxy pantothenate (EDCEP), on a diesel particulate extract (DPE) as a representative environmental pollutant that generates reactive oxygen species (ROS) through the activation of aryl hydrocarbon receptor (AHR) signaling. METHODS: We characterized the effects of PA and EDCEP on normal human epidermal keratinocytes (NHEKs) exposed to DPE or H2O2 as a general oxidative stress stimulator. Cell viability and intracellular ROS levels were evaluated using the 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) assay, respectively. Further, we investigated the substantial effects and the underlying mechanism of EDCEP, which elicited a reduction of intracellular ROS. RESULTS: PA and EDCEP restored the decreases of cell viability induced by DPE and also repressed the up-regulation of CYP1A1 mRNA expression induced by DPE. Interestingly, the effects of PA and EDCEP on intracellular ROS levels showed different responses. EDCEP reduced intracellular ROS levels stimulated by DPE or by exposure to H2O2. EDCEP suppressed the secretion of tumor necrosis factor (TNF-α) and reduced the level carbonylated proteins in reconstructed human epidermal equivalents topically treated with DPE. EDCEP up-regulated the mRNA expression levels of nuclear factor E2-related factor 2 (Nrf2), γ-glutamyl cysteine synthase (γ-GCS), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and in addition, increased intracellular glutathione (GSH) levels. CONCLUSION: EDCEP reduces cellular damage initiated by environmental pollutants by stimulating the intracellular defense system against ROS through the activation of Nrf2, and by interfering with AHR signaling pathway activation.

Chimyl Alcohol Suppresses PGE2 Synthesis by Human Epidermal Keratinocytes through the Activation of PPAR-γ.

Alkyl glyceryl ethers (AKGs) are widely used as emulsion stabilizers, and their anti-inflammatory effects are well known. Daily exposure to environmental stresses, such as chemicals, low humidity and ultraviolet light (UV), can initiate and promote the development of various skin problems. Among those stresses, it has been established that UV induces skin pigmentation and accelerates premature skin aging due to the inflammation that results. Here, we investigated whether chimyl alcohol (CA), which is an AKG, suppresses the inflammatory process. The suppression of cell damage and the reduction of intracellular levels of reactive oxygen species (ROS) in normal human epidermal keratinocytes (NHEKs) after UVB exposure was evaluated using the Neutral red (NR) and the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) assays, respectively. Moreover, the expression levels of mRNAs and proteins related to inflammation were evaluated by Real-time RT-PCR and ELISA assays, respectively. CA suppressed prostaglandin E2 (PGE2) production in UVB-exposed NHEKs according to the down-regulated expression level of cyclooxygenase-2 (COX-2) mRNA. Furthermore, CA up-regulated the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-γ, nuclear factor E2-related factor 2 (Nrf2) and γ-glutamyl cysteine synthase (γ-GCS) in NHEKs. Finally, we examined the effects of CA on siPPAR-γ transfected NHEKs. siPPAR-γ transfection of NHEKs abolished the mRNA expression levels of Nrf2 and UVB-stimulated PGE2 secretion that were regulated by CA. Hence, CA suppresses the UVB-induced COX-2 mRNA expression and PGE2 production through PPAR-γ as an agonist. We conclude that CA provides useful protection and/or alleviation against UV damage.

Dihydroresveratrol cellobioside and xylobioside as effective melanogenesis activators.

Dihydroresveratrol cellobioside and xylobioside, whose structures were designed based on that of the naturally occurring melanogenesis-controlling agent dihydroresveratrol glucoside, were synthesized via Schmidt glycosylation as the key step. Both analogues stimulated melanogenesis with efficacies comparable to that of 8-methoxypsoralen, a well-known melanogenesis activator. This suggests that diglycosyl modification of the 4'-OH on the dihydroresveratrol skeleton leads to the activation of melanogenesis, both with and without hydroxymethyl groups in the sugar moieties.

Synthesis of dihydroresveratrol glycosides and evaluation of their activity against melanogenesis in B16F0 melanoma cells.

Dihydroresveratrol glucoside 1 isolated from Camellia oleifera and its xyloside derivative 2 were synthesized for the first time in 5 steps from TBS-protected aldehyde 4. Natural product 1 is a potent melanogenesis inhibitor in B16F0 melanoma cells (approximately 40 fold more potent than kojic acid). In contrast, the synthetic product 2 stimulates melanogenesis, suggesting that a single hydroxymethyl group in the glycoside substituent of dihydroresveratrols is responsible for inhibition or activation of melanogenesis.

The possible involvement of skin dryness on alterations of the dermal matrix.

Moisturization of the skin plays an important role in maintaining skin homeostasis. Although it is understood that skin dryness initiates the formation of fine wrinkles, there are few objective reports to support that understanding. The purpose of this study was to establish an in vitro dry epidermal model using reconstructed human epidermal equivalents (RHEEs) and to elucidate the relationship between skin dryness and alterations of the dermal matrix which is one of the causes for the formation of wrinkles. An in vitro dry epidermal model was prepared by loading a CaCl2 -filled ampoule on the surface of an RHEE. To evaluate whether the in vitro model reproduced the characteristics of in vivo skin dryness, histological studies and biological assays using a protein array were carried out. Histologically, a distinct fluorescence which originated from carbonylated protein was observed in the stratum corneum. In addition, conditioned medium from RHEEs cultured under dry conditions for 24 h revealed the secretion of several proteins, such as IL-1α, IL-1ra, IL-8, MMP-9, VEGF, M-CSF and IGFBP-2 and IGFBP-3, galectin-1, Cys-C, FGF-6, OPG, Glc and TSP4 compared with normal RHEEs. It has been reported that an increase in IL-1α and the accumulation of carbonylated proteins are observed in the intact stratum corneum in the low humidity winter season. Thus, the in vitro dry epidermal model expresses the features of in vivo skin dryness observed in the winter season. Furthermore, the conditioned medium from RHEEs cultured under dry conditions enhanced MMP-1 secretion by normal human dermal fibroblasts. Taken together, we propose the hypothesis that skin dryness contributes to alterations of the dermal matrix through the elevation of MMP-1 secretion.

Women's impressions of their inpatient birth care as provided by family physicians in the Shizuoka Family Medicine Training Program in Japan.

BACKGROUND: Even though Japan faces serious challenges in women's health care such as a rapidly aging population, attrition of obstetrical providers, and a harsh legal climate, few family medicine residency training programs in Japan include training in obstetrics, and the literature lacks research on women's views of intra-partum pregnancy care by family physicians. FINDINGS: In this exploratory study, we conducted semi-structured qualitative interviews with five women who received their admission, intrapartum, delivery and discharge care from family medicine residents in the obstetrics ward of a community training hospital. Four women had vaginal births, and one had a Cesarean section. Three were primiparous, and two multiparous. Their ages ranged from 22-33. They found value in family physician medical knowledge and easy communication style, though despite explanation, some had trouble understanding the family physician's scope of work. These women identified negative aspects of the hospital environment, and wanted more anticipatory guidance about what to expect physically after birth, but were enthusiastic about seeing a family doctor after discharge. CONCLUSIONS: These results demonstrate the feasibility of family medicine residents providing inpatient birth care in a community hospital, and that patients are receptive to family physicians providing that care as well after discharge. Women's primary concerns relate mostly to hospital environment issues, and better understanding the care family physicians provide. This illustrates-areas for family physicians to work for improvements.