Y Takema’s research while affiliated with Kao Corporation and other places

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Publications (25)


Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis
  • Article

June 2016

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64 Reads

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42 Citations

Journal of the European Academy of Dermatology and Venereology

S. Ito

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J. Ishikawa

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A. Naoe

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[...]

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Y. Takema

Background: Ceramide is a crucial lipid in the stratum corneum (SC) which maintains the barrier function and hydration of the skin. In atopic dermatitis (AD) patients who have defective skin barrier function, ceramide levels are altered. We previously reported that although the amount of total ceramide was lower in involved skin compared with uninvolved skin of AD patients and with healthy control skin, the amounts of smaller ceramide species of Cer[NS] (<40 total carbons, which are total carbons of both sphingoid base and amide-linked fatty acid), especially Cer[NS] with 34 total carbons (C34-Cer[NS]), were higher. However, the enzyme(s) that produces the higher levels of smaller ceramide species in involved skin of AD patients was unclear. Objective: To identify the enzyme(s) that produces higher levels of smaller ceramide species of Cer[NS] in the involved skin of AD patients. Methods: Eight female Caucasian subjects who were diagnosed with AD on their arms (age range: 21-45 years) were enroled in this study. We compared ceramide levels in the SC and the expression levels of enzymes involved in ceramide metabolism using real-time PCR and immunohistochemistry between involved and uninvolved skin of AD patients. Results: Level of mRNA encoding ceramide synthase 4 (CERS4), which is one of the enzymes that synthesize ceramide from a sphingoid base and an amide-linked fatty acid, was significantly higher in involved skin than in uninvolved skin (P < 0.01). Additionally, the protein expression level of CERS4 in the epidermis was also higher in involved skin compared with uninvolved skin. The expression level of CERS4 correlated with the amount of C34-Cer[NS] (P < 0.01) and the skin hydration value (P < 0.05). Conclusions: The elevated expression level of CERS4 contributes to the increase of C34-Cer[NS] and the impaired SC barrier function in involved skin of AD patients.


The relationship between skin aging and steady state ultraweak photon emission as an indicator of skin oxidative stress in vivo

November 2013

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42 Reads

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12 Citations

Ultraweak photon emission (UPE) is one potential method to evaluate the oxidative status of the skin in vivo. However, little is known about how the daily oxidative stress of the skin is related to skin aging-related alterations in vivo. We characterized the steady state UPE and performed a skin survey. We evaluated the skin oxidative status by UPE, skin elasticity, epidermal thickness and skin color on the inner upper arm, the outer forearm, and the buttock of 70 Japanese volunteers. The steady state UPE at the three skin sites increased with age. Correlation analysis revealed that the steady state UPE only from the buttock was related to skin elasticity, which showed age-dependent changes. Moreover, analysis by age group indicated that b* values of the inner upper arm of subjects in their 20s were inversely correlated with UPE as occurred in buttock skin. In contrast, photoaged skin did not show a clear relationship with steady state UPE because the accumulation of sun-exposure might influence the sensitivity to oxidative stress. These results suggest that steady state UPE reflects not only intrinsic skin aging and cutaneous color but also the current oxidative status independent of skin aging.


Keratins of the human occipital hair medulla: Androgenic regulation of in vitro hair keratin K37 expression

February 2013

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64 Reads

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6 Citations

British Journal of Dermatology

The medulla is the innermost structure of the mammalian hair fibre. Unlike most mammals, in man only androgen-dependent sexual hairs, i.e. beard, pubic and axillary hairs, are regularly medullated, while the frequency of medullation in scalp hairs varies among individuals and ethnicities(1,2) . Recently, we reported that out of the 54 human keratins,12 epithelial keratins [comprising members of the outer and inner root sheath (ORS, IRS), the companion layer (cl), and the almost ubiquitously expressed keratin K80(3) , as well as 12 hair cortex keratins] are present in the medulla of beard hairs(4) .


Eucalyptus increases ceramide levels in keratinocytes and improves stratum corneum function

June 2011

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460 Reads

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29 Citations

International Journal of Cosmetic Science

Synopsis The objectives of this study were to identify a plant extract that would improve stratum corneum functions and to elucidate the mechanism(s) involved. Based on the information that stratum corneum functions depend on the level of ceramide in the stratum corneum, we identified a Eucalyptus extract that was able to increase the level of ceramide in human keratinocytes in culture and in human stratum corneum and that improves the stratum corneum water holding and barrier functions. Addition of the Eucalyptus extract to human keratinocytes in culture increased the level of ceramide in a dose‐dependent manner and also increased the biosynthesis of ceramide, glucosylceramide and sphingomyelin. Topical application of the Eucalyptus extract on the dry skin of human subjects induced by acetone and diethylether treatment resulted in a significant increase in ceramide level in the stratum corneum, a significant improvement in its water‐holding function and an improvement in its barrier function. The addition of macrocarpal A, one of the main components of the Eucalyptus extract, to human keratinocytes in culture increased the level of ceramide and the mRNA expression of serine palmitoyltransferase, acid sphingomyelinase, neutral sphingomyelinase, glucosylceramide synthase and glucocerebrosidase in a dose‐dependent manner. Our results indicate that the increased content of ceramides in the stratum corneum may underlie the therapeutic effect of the Eucalyptus extract. Our results also indicate the possibility that macrocarpal A is the key component that stimulates the synthesis of ceramide in the stratum corneum.


Real‐life use of underwear treated with fabric softeners improves skin dryness by decreasing the friction of fabrics against the skin

June 2011

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63 Reads

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11 Citations

International Journal of Cosmetic Science

Synopsis Scientific evaluation of fabric softener use on the friction of fabrics and on dry skin in real life is very limited. The coefficient of friction of fabrics was measured with a surface tester using model skin and cotton fabrics. The effects and safety of fabric softener-treated T-shirts on subjects with dry skin were evaluated in real-life conditions in the cold and arid environment. Twenty male volunteers with dry skin used T-shirts without softener for 1 week before day 0 and then wore softener-treated T-shirts for 14 days. Effects were evaluated by clinical grading, subjective symptoms, stratum corneum water content (SCWC) and transepidermal water loss (TEWL). A significant decrease in the coefficient of friction of fabrics was detected. A significant improvement in SCWC was observed on the torso, waist and shoulder, but no improvement was found on the inner forearm. There was a slight change in TEWL. The visual grading of dryness improved significantly at all sites, but no significant change was found in subjective symptoms. Our results suggest that fabric softener provides benefits to individuals with dry skin because of the decreased friction of the garments against the skin. It is possible that the softener treatment of fabrics contributes to the state of moisturization of the skin and may work in collaboration with the application of moisturizers. © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.



Figure 1 Immunocytochemistry on human epidermis 7 days after transduction with pseudotyped HIV-based vectors expressing b-galactosidase. Each vector was administered twice and xenografts were analyzed by immunocytochemistry 7 days after the last injection. (a) and (b) VSV-G, (c) and (d) EboZ, (e) and (f) MuLV, (g) and (h): LCMV, (i) and (j) Rabies, (k) and (l) Mokola, and (m) and (n) Ad-LacZ. Immunocytochemistry staining of the grafted human skin was performed with a rabbit polyclonal antibody recognizing the E. coli b-galactosidase (red) (a, c, e, g, i, k and m) and merged with a monoclonal antibody specific for human involucrin (green) (b, d, f, h, j, l and n) as detailed in 'Materials and methods'. Bar ¼ 50 mm.
Figure 2 Immunocytochemistry on human dermis 7 days post-transduction with pseudotyped HIV-based vectors expressing b-galactosidase. Each vector was administered twice and xenograft was analyzed by immunocytochemistry 7 days following the last injection. (a-c) VSV-G, (d-f) EboZ, (g-i) MuLV, and (j-l) adenovirus. Immunocytochemistry staining of grafted human skin was performed with a rabbit polyclonal antibody recognizing the E. coli b-galactosidase (red) and a monoclonal antibody specific for human fibroblast (green) as detailed in 'Materials and methods'. Merging images were presented in (c), (f), (i) and (l). Bar ¼ 50 mm.
Figure 3 b-Galactosidase expression is observed in column in epidermis treated with VSV-G-, EboZ-, or MuLV-pseudotyped lentiviral vectors 4 week after the second injection. (a) and (b) VSV-G, (c) and (d) EboZ, (e) and (f) MuLV, and (g) and (h) adenovirus. Immunofluorescence staining of grafted human skin intradermally injected with pseudotyped HIV vectors encoding E. coli b-galactosidase 4 week after the second injection was performed with a rabbit polyclonal antibody that recognizes E. coli b-galactosidase (red) and a monoclonal antibody specific for human involucrin (green) (a, c, e and g) or a monoclonal antibody specific for human integrin b1 (green) (b, d, f and h) as detailed in 'Materials and methods'. Bar ¼ 50 mm.
Figure 4 Hematoxylin nuclei staining of EboZ-or LCMV-pseudotyped vector treated human skin. Grafted human skin intradermally injected with HIV vector pseudotyped with VSV-G (a), EboZ (b) or LCMV (c) expressing b-galactosidase were embedded in paraffin and analyzed following hematoxylin and eosin staining 28 days after the last injection. Tissue degenerations in the architecture of the dermis are visible as dark red areas. Bar ¼ 100 mm.
Figure 5 b-galactosidase staining of human skin xenografts transduced with HIV-based vector pseudotyped with different envelope glycoproteins. (a) and (b) PBS, (c) and (d) VSV-G, (e) and (f) EboZ, and (g) and (h) MuLV. b-galactosidase staining of grafted human skin was performed 24 h post-intradermal injection. Bars ¼ 3 mm in a, c, e, and g (top views) and bars ¼ 1 mm in b, d, f, and h (side views).

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Gene transfer in human skin with different pseudotyped HIV-based vectors
  • Article
  • Full-text available

May 2007

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99 Reads

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30 Citations

Gene Therapy

Pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. In this study, the modification of HIV vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (VSV), the Zaire Ebola (EboZ) virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), Rabies or the rabies-related Mokola virus encoding LacZ as a reporter gene was evaluated qualitatively and quantitatively in human skin xenografts. High transgene expression was detected in dermal fibroblasts transduced with VSV-G-, EboZ- or MuLV-pseudotyped HIV vector with tissue irregularities in the dermal compartments following repeated injections of EboZ- or LCMV-pseudotyped vectors. Four weeks after transduction, double-labeling immunofluorescence of beta-galactosidase and involucrin or integrin beta1 demonstrated that VSV-G-, EboZ- or MuLV-pseudotyped HIV vector effectively targeted quiescent epidermal stem cells which underwent terminal differentiation resulting in transgene expression in their progenies. Among the six different pseudotyped HIV-based vectors evaluated, VSV-G-pseudotyped vector was found to be the most efficient viral glycoprotein for cutaneous transduction as demonstrated by the highest level of beta-galactosidase expression and genome copy number evaluated by TaqMan PCR.

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Figure 2 Immunocytochemistry on human dermis 7 days post-transduction with pseudotyped HIV-based vectors expressing b-galactosidase. Each vector was administered twice and xenograft was analyzed by immunocytochemistry 7 days following the last injection. (a-c) VSV-G, (d-f) EboZ, (g-i) MuLV, and (j-l) adenovirus. Immunocytochemistry staining of grafted human skin was performed with a rabbit polyclonal antibody recognizing the E. coli b-galactosidase (red) and a monoclonal antibody specific for human fibroblast (green) as detailed in 'Materials and methods'. Merging images were presented in (c), (f), (i) and (l). Bar ¼ 50 mm.
Figure 4 Hematoxylin nuclei staining of EboZ-or LCMV-pseudotyped vector treated human skin. Grafted human skin intradermally injected with HIV vector pseudotyped with VSV-G (a), EboZ (b) or LCMV (c) expressing b-galactosidase were embedded in paraffin and analyzed following hematoxylin and eosin staining 28 days after the last injection. Tissue degenerations in the architecture of the dermis are visible as dark red areas. Bar ¼ 100 mm.
Figure 5 b-galactosidase staining of human skin xenografts transduced with HIV-based vector pseudotyped with different envelope glycoproteins. (a) and (b) PBS, (c) and (d) VSV-G, (e) and (f) EboZ, and (g) and (h) MuLV. b-galactosidase staining of grafted human skin was performed 24 h post-intradermal injection. Bars ¼ 3 mm in a, c, e, and g (top views) and bars ¼ 1 mm in b, d, f, and h (side views).
Figure 6 The integrated E. coli b-galactosidase copy number and b-galactosidase activity is the highest in the skin treated with VSVG-pseudotyped lentiviral vector compared to the rest of viral vectors. (a) The integrated E. coli b-galactosidase copy number was analyzed after genomic DNA was extracted from each tissue using a DNeasy kit as detailed in 'Materials and methods'. The values represent mean7s.d. of integrated copy number per 100 ng of total DNA from three to four individual grafted skins. (b) b-galactosidase activity was evaluated after pulverized biopsies were lysed in buffer for b-galactosidase assay as detailed in 'Materials and methods'. The values represent the mean7s.d. from three to four individual grafted skins. The activity in the skin treated with VSV-Gpseudotyped lentiviral vector was significantly (Po0.05) higher than those of the rest of viral vectors and the activities in the skin treated with EboZ-and MuLV-pseudotyped lentiviral vector were also significantly (Po0.05 and Po0.01, respectively) higher than the PBS control.
Gene transfer in human skin with different pseudotyped HIV-based vectors

April 2007

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88 Reads

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12 Citations

Gene Therapy

Pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. In this study, the modification of HIV vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (VSV), the Zaire Ebola (EboZ) virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), Rabies or the rabies-related Mokola virus encoding LacZ as a reporter gene was evaluated qualitatively and quantitatively in human skin xenografts. High transgene expression was detected in dermal fibroblasts transduced with VSV-G-, EboZ- or MuLV-pseudotyped HIV vector with tissue irregularities in the dermal compartments following repeated injections of EboZ- or LCMV-pseudotyped vectors. Four weeks after transduction, double-labeling immunofluorescence of β-galactosidase and involucrin or integrin β1 demonstrated that VSV-G-, EboZ- or MuLV-pseudotyped HIV vector effectively targeted quiescent epidermal stem cells which underwent terminal differentiation resulting in transgene expression in their progenies. Among the six different pseudotyped HIV-based vectors evaluated, VSV-G-pseudotyped vector was found to be the most efficient viral glycoprotein for cutaneous transduction as demonstrated by the highest level of β-galactosidase expression and genome copy number evaluated by TaqMan PCR.


Age-related changes in the three-dimensional morphological structure of human facial skin

October 2006

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31 Reads

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39 Citations

Background/aims The human face shows morphological changes with age. Although these changes are generally recognized as wrinkle formation, there have been no quantitative studies of three‐dimensional morphological changes with age in each area of the face. The object of the present study, therefore, was to evaluate age‐related three‐dimensional morphological changes in each area of the face. Methods We obtained replicas using a silicon impression material from eight areas of the face (forehead, eye corners, upper eyelids, lower eyelids, glabella, cheeks, mouth angles, and nasolabial groove) of 136 healthy women, and performed morphological evaluations using a small object type three‐dimensional surface morphology measurement system (Voxelan, NKK Co. Ltd., Japan). Results All parameters examined, with the exception of sWv in the cheeks, increased with age. The correlation between sWp and age was high in the following order: eye corners > mouth angles > glabella > nasolabial groove > upper eyelids > lower eyelids > forehead > cheeks. sWp in all areas except the eye corners was similar to the mean value in the cheeks in the group aged 18‐20 years. However, in the group aged 71‐83 years, marked differences were observed among the eye corners, glabella, mouth angles, nasolabial groove, and upper eyelids. Conclusion: Although sunlight is important in the development of three‐dimensional changes in surface morphology (wrinkles) in the face, other factors seem to play important roles for the progression of these changes.


The formation of wrinkles caused by transition of keratin intermediate filaments after repetitive UVB exposure

March 2005

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60 Reads

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29 Citations

Archives of Dermatological Research

It has been reported that the formation of wrinkles involves changes in the elastic properties of the dermis due to the denaturation of elastic fibers. Several studies have shown that the hydration condition of the stratum corneum is also important in wrinkle formation. It is, however, still unclear how the stratum corneum contributes to wrinkle formation. Here we investigated the relationship between the formation of wrinkles and changes in the physical properties and condition of the skin after repetitive ultraviolet B (UVB) irradiation of hairless mice (HR/ICR). Repetitive UVB irradiation caused wrinkles on the dorsal skin of the mice. The elasticity (E') of the stratum corneum of UVB-irradiated mice was significantly lower than that of age-matched control (unirradiated) mice. UVB exposure also caused a deterioration of the fibrous ultrastructure of keratin intermediate filaments (KIFs) in the skin. We conclude that the deterioration of KIFs in the stratum corneum caused by repetitive UVB irradiation decreases the elastic properties of the stratum corneum, resulting in the formation of wrinkles.


Citations (19)


... We next investigated the association between the mRNA expression of specific ceramide synthesis-related enzymes and the levels of the corresponding lipids. Five types of ceramide synthase 2-6 (CERS 2-6) have been identified in human keratinocytes and are known to be involved in the skin barrier alteration associated with AD (Ito et al., 2017). Figure 4 displays the gene expression of CERS3, 4, and 6, which are involved in the synthesis of the Cer [NS] class, and the abundance profile of their corresponding member with specific FA chain lengths (Park et al., 2010;Cingolani et al., 2016). ...

Reference:

Effects of Th1/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes
Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis
  • Citing Article
  • June 2016

Journal of the European Academy of Dermatology and Venereology

... Biological autoluminescence (BAL) is known to be generated by electronically excited states of molecules in biosystems (Burgos et al. 2017;Wang et al. 2015;Gabe et al. 2014;Cilento and Adam 1995;Van Wijk 1992;Nakamura and Hiramatsu 2005;Okano et al. 2001;Rastogi and Pospísil 2011;Cifra and Pospíšil 2014;Cadenas and Sies 1984;Boveris et al. 1980;Nakano 1989). The typical intensity is <1000 photons•s -1 •cm -2 . ...

The relationship between skin aging and steady state ultraweak photon emission as an indicator of skin oxidative stress in vivo
  • Citing Article
  • November 2013

... The averages of normalized transcripts of THBD, THEMIS2, SERPINA1, PIK3CG, and VAV1 were used as an estrogen response proxy. Androgen levels were estimated using the transcript levels of KRT37 as a proxy [126]. Sperm-associated HSP levels were calculated by averaging the three normalized transcripts of sperm HSPs, including HSPA6, HSP90B1, and DNAJB1 [58,59]. ...

Keratins of the human occipital hair medulla: Androgenic regulation of in vitro hair keratin K37 expression
  • Citing Article
  • February 2013

British Journal of Dermatology

... Notably, the most representative phenomena of aging is wrinkles, and wrinkles, especially around the eyes, are the first to occur during aging [14,15]. The early occurrence of wrinkles near the eyes is attributed to the fact that the periorbital skin is the thinnest facial skin, experiences constant movement caused by blinking, has reduced subcutaneous fat, and is exposed to ultraviolet rays [14,16]. ...

Age-related changes in the three-dimensional morphological structure of human facial skin
  • Citing Article
  • October 2006

... Chung et al. (2001), reported that women have a greater risk of developing wrinkles than men after controlling for sun exposure and smoking, and considered post-menopausal decreases in female hormones as a contributory factor. Female hormonal decreases heighten the UV sensitivity of the skin and wrinkle progression is significantly increased with long-term UV exposure, suggesting that female hormones may suppress UV-induced increases in wrinkle development (Tsukahara et al., 2004). ...

Ovariectomy is sufficient to accelerate spontaneous skin aging and to stimulate UV-induced photoaging of murine skin
  • Citing Article
  • November 2004

British Journal of Dermatology

... Compared with chemically synthesized cosmetics, natural active substances extracted from natural plants, herbs, marine organisms, etc., have the advantages of being more natural, pure, and hypoallergenic. In particular, they have strong beneficial effects on the skin, such as UV radiation protection, antioxidant activity (14)(15)(16), regulating epidermal protection barrier (17-19) and maintaining water-ion balance (20, 21). Natural active substances, including aloin (22,23), ginsenosides (24,25), hydroxycinnamic acids (26,27), and astaxanthin (ASX) (28, 29) have been proven to effectively solve a series of skin problems. ...

Eucalyptus increases ceramide levels in keratinocytes and improves stratum corneum function
  • Citing Article
  • June 2011

International Journal of Cosmetic Science

... AE 3.0 a.u., respectively (Table I). These values are consistent with those of healthy subjects reported in previous studies [30][31][32][33], which confirmed that all subjects in this study had healthy skin. We examined the relationships of the baseline, initial peak, Slope-MAX (maximum change in SkBF) and nadir (Fig. 1A to D), which are indices based on SkBF changes during local warming, with capacitance and with TEWL. ...

Real‐life use of underwear treated with fabric softeners improves skin dryness by decreasing the friction of fabrics against the skin
  • Citing Article
  • June 2011

International Journal of Cosmetic Science

... For this purpose carriers equipped with penetrating peptides or viral vectors seems to be more adequate. For example, Hachiya et al. [80] evaluated the feasibility of gene transfer to follicular stem cells using HIV-based vectors and, in an experiment by Zhao et al. [81], the cutaneous delivery of the tyrosinase-gene pLme/SN by means of retrovirus resulted in melanin production in albino rats. Gene transfer to hair follicle cells has also been used to treat pigmentation and hair growth disorders [76]. ...

Gene transfer in human skin with different pseudotyped HIV-based vectors

Gene Therapy

... Skin biomechanical evaluation is performed by a Cutometer® dual MPA 580 (Courage + Khazaka Electronic GmbH, Koln, Germany) using a 2-mm-diameter probe [29]. This system is used to measure elasticity and firmness of the skin using negative pressure, which deforms the skin mechanically. ...

Age-related changes in the elastic properties and thickness of facial skin
  • Citing Article
  • December 1994

British Journal of Dermatology

... Facial wrinkles and folds are a result of the ageing process. Pathophysiology of ageing is due to the degeneration of collagen fibres and accumulation of altered elastic fibers in the dermis. 1 There are many intrinsic and extrinsic factors that trigger facial ageing: sun exposure, hereditary, nutritional, stress, alcoholism, smoking, drug abuse, pollution etc. 2,3 Age-related changes in the face like dermal dystrophy, dermal thickening, facial soft tissue loss, loss of subcutaneous tissue and redistribution of fat will contribute to facial folds. Crow's feet and nasolabial folds are the first sign of facial ageing. ...

The Effects of UVA and UVB Irradiation on the Viscoelastic Properties of Hairless Mouse Skin in vivo
  • Citing Article
  • February 1998

Dermatology