Increase In Skin Thickness Research Articles

Effect of Mold Temperature on Morphology and Mechanical Properties of Injection Molded HDPE Structural Foams

In this study, HDPE structural foams are produced by injection molding under different mold temperatures to study the effect of this variable on average cell dimension, cell density, and skin thickness ratio. Samples are also produced by setting independently the temperature of the fixed and moving plate of the mold to detect the sensitivity of foam structure to a temperature gradient in processing. The resulting foams are also characterized in terms of mechanical properties including impact and flexural tests. It has been found that for homogeneous mold temperatures, symmetrical skin thicknesses are obtained, which increase with decreasing mold temperature. On the other hand, by keeping one mold face at a constant temperature and varying the second one, asymmetric skin thicknesses are obtained. The degree of asymmetry is found to increase as the temperature difference between both molds increased. Furthermore, decreasing mold temperature produces a small increase in average cell sizes and reduced cell density. In general, both impact strength and flexural moduli of the structural foams increase with increasing skin thickness. For the particular case of asymmetric foams, the flexural moduli are slightly higher when the load is applied on the thicker skin; while much higher impact strength is obtained when the falling weight strikes the samples on the face having the smaller skin thickness.

Oral Administration of KTNG0345 Prepared from Red Ginseng Extracts Reduces UVB-induced Skin Wrinkle Formation in Hairless Mice

Chronic ultraviolet (UV) exposure is the major cause of photoaging that causes skin wrinkling, roughness, dryness, laxity, and pigmentation. Recently, increasing efforts are being made to understand the relationship between foods and skin health. Ginsenosides are present in ginseng (Ginseng Radix Rubra) extract, and are known to have biomedical properties, such as, anti-oxidant and anti-inflammatory effects. In this study, we investigated whether KTNG0345 prepared from red ginseng extracts delivered orally reduces skin wrinkling and ultraviolet B (UVB)-induced wrinkle formation in hairless mouse skin. KTNG0345 was administrated orally to the mice (5 times a week) during the period of UVB-irradiation (3 times a week) for 8 weeks at three different doses of 300 mg/kg, 500 mg/kg and 1000 mg/kg (w/v). UV doses were increased weekly by 1 MED (1MED = 75 <TEX>$mJ/cm^2)$</TEX> up to 4 MED and then maintained at this level. After the 8-week administration period, it was found that orally administered KTNG0345 significantly inhibited UVB-induced wrinkle formation in a dose-dependent manner. Increases in skin thickness caused by UVB were prevented by KTNG0345. Moreover, it also significantly inhibited matrix metalloproteinases (MMP) -13 and MMP-9 expressional inductions by UVB. In addition, KTNG0345 was observed to prevent UVB-induced water loss of epidermis in hairless mouse skin. Our results demonstrate that orally administered KTNG0345 has anti-wrinkling effects in hairless mouse skin, and suggest that dietary red ginseng and herbal mixture may be considered a functional beauty food for preventing UVB-induced skin wrinkles.

SAG/ROC2/RBX2 E3 ligase promotes UVB-induced skin hyperplasia, but not skin tumors, by simultaneously targeting c-Jun/AP-1 and p27

Sensitive to apoptosis gene (SAG)/regulator of cullins-2/RING box protein 2 is a stress-responsive RING component of Skp-1/Cullins/F-box protein E3 ubiquitin ligase. When overexpressed, SAG inhibits apoptosis induced by reactive oxygen species or hypoxia. Here, we report that SAG overexpression inhibits ultraviolet (UV) B-induced apoptosis in mouse JB6 epidermal cells. Using a transgenic mouse model, in which SAG expression was targeted primarily to epidermis by a K14 promoter, we showed that, at the early stage of UVB skin carcinogenesis (10 weeks post-UVB exposure), c-Jun, p27, p53, c-Fos and cyclin D1 were strongly induced. While having no effect on UVB-induced p53, c-Fos and cyclin D1, SAG-transgenic expression reduced the levels of c-Jun and p27 and inhibited AP-1 activity. The net outcome of SAG-mediated inhibition of c-Jun/AP-1 (pro-tumor promotion) and of p27 (antiproliferation) increased skin hyperplasia, with no apparent effect on apoptosis, as evidenced by increased skin thickness, and increased rate of DNA synthesis, but hardly any apoptosis. Although skin hyperplasia was promoted, SAG-transgenic expression had no significant effect on tumor formation in the later stage of UVB carcinogenesis. Thus, by simultaneously targeting c-Jun and p27, SAG accelerates UVB-induced skin hyperplasia, but not carcinogenesis.

Einsatz biophysikalischer Messverfahren zur Untersuchung der hautphysiologischen Wirkung injizierbarer Hyaluronsäure

To evaluate the effects of intradermal injection of native hyaluronic acid on physiology of aged skin using bioengineering methods. 10 female patients aged 44-69 were included. Study duration was 24 weeks. Each patient received 3 treatments (at week 0, 2 and 4) with native hyaluronic acid (Hyalsystem Merz Pharmaceuticals, Frankfurt/Main, Germany) and 4 examinations (week 0, 4, 12 and 24). Biophysical properties assessed were skin elasticity and surface roughness, as well as skin thickness and density. Skin elasticity increased while skin surface roughness was reduced. High frequency ultrasound revealed an increase of skin thickness, whereas skin density decreased during treatment and slightly increased above baseline at week 24. The evaluation of the effects of an intradermal injection of hyaluronic acid on aged skin showed an improvement of skin elasticity and skin surface roughness.

Activity of a cationic carotenoid derivative in a mouse model of protoporphyria

Prior work using cell culture has shown that certain synthetic carotenoid derivatives are more effective than natural carotenoids in preventing photosensitized cell killing. These carotenoid derivatives are either cationic or are weak bases. We have now found that of one of these derivatives, the Girard’s reagent T derivative of β-apo-8′-carotenal (GRT-carotenal) decreases acute photosensitivity in a mouse model of protoporphyria. When GRT-carotenal was added to the diet of SKH1 mice, both GRT-carotenal and its metabolites accumulated in the skin of the mice. Protoporphyria was induced in SKH1 mice by adding collidine to their diet. When the porphyric mice were exposed to 400 nm light (2.6 ± 0.1 mW cm −2) for a period of 2 h, the skin on the backs of these animals increased in thickness. Increased vascularity also developed in the skin of the mouse ears. Animals, that were fed a diet containing both collidine and GRT-carotenal and then exposed to light, had significantly smaller increases in skin thickness and less prominent increases in the vascular pattern on their ears.

Clinical and echographic analysis of photodynamic therapy using methylaminolevulinate as sensitizer in the treatment of photodamaged facial skin

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) has been previously investigated in the treatment of photodamaged skin. The aim was to assess efficacy and tolerability of methylaminolevulinate (MAL) as a substitute for ALA in PDT treatment of actinic keratosis (AK) and photoaging. Twenty patients with multiple (n = 137) AKs and severe photodamage of the face were treated. Metvix (Galderma, France) was applied under occlusion for 3 hours before exposure to 37 J/cm(2) of red light (Aklilite CL 128, Photocure, Norway). Two treatments were given at monthly intervals. The clearance rate of AKs was 88.3%, and global score which we use to rate photoaging, mottled hyperpigmentation, fine lines, roughness, and sallowness of the skin showed improvement, but deep wrinkles, teleangiectasia, facial erythema, and sebaceous gland hypertrophy did not change. The treatments were well tolerated. High-resolution echography showed an increase in skin thickness, pixels count and area, as well as a reduction of the subepidermal low-echogenic band (SLEB) thickness. MAL-PDT is an effective treatment for multiple AKs. In addition, it improves clinical signs of photodamage of the surrounding skin.

Cutaneous Gene Expression by DNA Microarray in Murine Sclerodermatous Graft-Versus-Host Disease, a Model for Human Scleroderma

The molecular mechanisms governing skin fibrosis in murine sclerodermatous graft-versus-host disease (Scl GVHD) are not known. We used Affymetrix DNA microarrays representing >14,000 mouse genes to characterize global gene expression in skin during development of Scl GVHD in lethally irradiated BALB/c (H-2d) mice transplanted with B10.D2 (H-2d) bone marrow and spleen cells. These mice develop skin thickening, whereas control mice transplanted with syngeneic BALB/c (H-2d) bone marrow and spleen cells do not develop disease. We found consistent differences between mice with Scl GVHD and controls in cytokine messenger RNAs (mRNAs) for both Th1-like (IFN-gamma) and Th2-like (IL-6, Il-10, and IL-13) inflammatory patterns. mRNAs for chemokines CCL2, CCL5, CCL17, IFN-gamma inducible chemokines (CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC), and for growth factors such as platelet-derived growth factor-c, connective tissue growth factor, fibroblast growth factor 1, epidermal growth factor, nerve growth factor-beta, vascular endothelial growth factor (VEGF)-alpha, and VEGF-beta were elevated, similar to human scleroderma. mRNAs for cell adhesion molecules, such as L-selectin (selectin lymphocyte), P-selectin (selectin platelet), E-selectin (selectin endothelium), and vascular cell adhesion molecule 1, were also upregulated. In separate experiments, we confirmed the increased synthesis of IFN-gamma and IL-2, unchanged IL-10, and absence of tumor necrosis factor-alpha, and IL-4 proteins by flow cytometry of isolated skin T cells. These constellations of immunologic changes provide a "fingerprint" for fibrosing autoimmune disease. They are useful to understand the pathogenesis of Scl GVHD, to identify markers for early diagnosis of disease, and to devise more effective strategies for intervention in early scleroderma and Scl GVHD.

Effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators

Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens prevent skin aging. They increase skin thickness and improve skin moisture. Beneficial effects of hormone replacement therapy (HRT) on skin aging have been well documented, but HRT cannot obviously be recommended solely to treat skin aging in menopausal women. Topical estrogen application is highly effective and safe if used by a dermatologist with expertise in endocrinology. The question of whether estrogen alternatives such as phytoestrogens and selective estrogen receptor modulators are effective estrogens for the prevention of skin aging in postmenopausal women remains unanswered. However, preliminary data indicate that such treatment may be of benefit for skin aging treatment.

Safety and Efficacy of Poly-L-lactic Acid Injections in Persons with HIV-Associated Lipoatrophy

BACKGROUND With the introduction of highly active antiretroviral therapy (HAART), HIV/AIDS has become a more chronic disease. This increase in survival, however, has been accompanied by the occurrence of metabolic and morphologic changes known collectively as HIV-associated lipodystrophy. OBJECTIVE The objective was to evaluate the quantifiable improvement in facial wasting (lipoatrophy) after serial injections of poly-L-lactic acid (PLLA) as well as the long-term safety and durability of this material. METHODS AND MATERIALS A single-site, open-label study in which patients received up to six treatment sessions of injectable PLLA. Patients were followed for 12 months after treatment. Patients were evaluated for increase in total cutaneous thickness by skin calipers. Serial photographs and patient satisfaction and patient well-being questionnaires were undertaken throughout the study period. RESULTS Patients at the end of treatment exhibited a mean increase in skin thickness of 65.1% compared with baseline values. This correction was maintained throughout the 12-month follow-up period (68.8% at 6 months and 73% at 12 months). On a one to five scale, patient satisfaction was 4.5 at the end of treatment and increased to 4.8 at 12-month follow-up. No serious adverse events were reported. CONCLUSION PLLA is a safe and well-tolerated treatment option for HIV-associated lipoatrophy.

Safety and Efficacy of Poly-l-lactic Acid Injections in Persons with HIV-Associated Lipoatrophy: The US Experience

With the introduction of highly active antiretroviral therapy (HAART), HIV/AIDS has become a more chronic disease. This increase in survival, however, has been accompanied by the occurrence of metabolic and morphologic changes known collectively as HIV-associated lipodystrophy. The objective was to evaluate the quantifiable improvement in facial wasting (lipoatrophy) after serial injections of poly-L-lactic acid (PLLA) as well as the long-term safety and durability of this material. A single-site, open-label study in which patients received up to six treatment sessions of injectable PLLA. Patients were followed for 12 months after treatment. Patients were evaluated for increase in total cutaneous thickness by skin calipers. Serial photographs and patient satisfaction and patient well-being questionnaires were undertaken throughout the study period. Patients at the end of treatment exhibited a mean increase in skin thickness of 65.1% compared with baseline values. This correction was maintained throughout the 12-month follow-up period (68.8% at 6 months and 73% at 12 months). On a one to five scale, patient satisfaction was 4.5 at the end of treatment and increased to 4.8 at 12-month follow-up. No serious adverse events were reported. PLLA is a safe and well-tolerated treatment option for HIV-associated lipoatrophy.

Inflammatory Murine Skin Responses to UV-B Light Are Partially Dependent on Endothelin-1 and Mast Cells

Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assessed skin responses to ET-1 injections, we observed prominent mast cell degranulation and mast cell-dependent inflammation. Since mast cells also critically contributed to UV-induced inflammation, we determined the ET-1-dependent inflammatory response to UV in the absence and presence of these cells. Interestingly, ETA blockade did not decrease UV-induced inflammation in mast cell-deficient mice, unless these mice had been adoptively transferred with mast cells before irradiation. This indicates that skin inflammation due to UV irradiation is caused in part by ET-1 acting on skin mast cells.

Effects of hormone replacement therapy and tıbolone on skın thıckness and bone ın postmenopausal women

Effects of hormone replacement therapy and tıbolone on skın thıckness and bone ın postmenopausal women

Prevention of UV Radiation‐Induced Premature Skin Aging in Hairless Mice by the Novel Compound Melanocin A

Repetitive exposure of the skin to UV radiation induces various harmful changes, such as thickening, wrinkle formation, inflammation and carcinogenesis. A variety of natural compounds and synthetic compounds have been studied to determine whether they can prevent UV-induced harmful effects. In this study, we investigated the effect of a novel compound, Melanocin A, which was isolated from Eupenicillium shearii F80695, on UV-induced premature skin aging. First, we studied the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT, in vitro. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated the effect of Melanocin A on UV-induced skin changes in hairless mice in vivo. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. Taken together, these results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging.

A novel analytical solution for a slug test conducted in a well with a finite-thickness skin

An aquifer containing a skin zone is considered as a two-zone system. A mathematical model describing the head distribution is presented for a slug test performed in a two-zone confined aquifer system. A closed-form solution for the model is derived by Laplace transforms and Bromwich integral. This new solution is used to investigate the effects of skin type, skin thickness, and the contrast of skin transmissivity to formation transmissivity on the distributions of dimensionless hydraulic head. The results indicate that the effect of skin type is marked if the slug-test data is obtained from a radial two-zone aquifer system. The dimensionless well water level increases with the dimensionless positive skin thickness and decreases as the dimensionless negative skin thickness increases. In addition, the distribution of dimensionless well water level due to the slug test depends on the hydraulic properties of both the wellbore skin and formation zones.

In Vivo Nitric Oxide Production and iNOS Expression in X-Ray Irradiated Mouse Skin

Inducible nitric oxide synthase (iNOS) and NO have been suggested to be involved in acute radiation response in tissues such as the liver, intestine, colon, and brain. However, direct measurement of NO and iNOS in ionizing radiation-induced skin inflammatory reactions is not reported yet. We show here for the first time, by in vivo experiments, that X-ray irradiated mouse skin generates NO with concomitant expression of iNOS at both the mRNA and protein levels. When irradiated at 50 Gy, iNOS mRNA appeared at day 8 post-irradiation, whereas iNOS protein could be detected only at day 14. No iNOS protein was detectable however for the mice receiving 5 or 15 Gy irradiation, even at day 14. Skin inflammatory reactions were observed at day 8 post-irradiation as an increase in skin thickness, which increased further by day 14. Histological observations showed acute inflammatory responses. The parallel relationship between iNOS induction and the onset of skin inflammatory reactions suggests the involvement of iNOS and NO in the skin damage. Immunohistochemical staining showed the localization of iNOS at skin erosion areas, exudate and infiltrating cells. Taken together, these findings suggest that iNOS induction and NO production in X-irradiated skin are relatively early events in skin inflammatory reactions and are probably secondary rather than primary reactions of irradiation.

Damage Characteristics of Composite Honeycomb Sandwich Panels in Bending under Quasi-static Loading

Damage characteristics of composite-skinned honeycomb sandwich panels in bending are investigated with both hemispherical (HS) and flat-ended (FE) indenters. The thickness of the cross-ply skins varies from 8 to 16 plies, whereas the density of the 12.7-mm thick aluminum honeycomb core varies from 50 to 70 kg/m3. Clamped panels with a 100-mm testing area are loaded quasi-statically either in bending or on a rigid base. The effects of varying these parameters on damage mechanisms are examined through response curves as well as cross sections of selected specimens. Special emphasis is placed on their potential change induced by the variation of skin thickness and core density with a specific indenter. Damage mechanisms are identified as core crush, top-skin delamination, and fracture or shear-out. The threshold and ultimate loads as well as the initial slope increase significantly either on increase of skin thickness or change of the nose shape of indenter from a hemisphere to a flat-end. The increase in the post-initial-damage slope is small and can be attributed to membrane stretching of the damaged top skin. Increasing the core density affects substantially not only the threshold load, but also the initial slope associated with the FE indenter. Changing the nose shape of the indenter has an overriding effect on the nature of damage mechanisms. In particular, top-skin delaminations occur after core crush. The panel deflection contributes to 20-53% sandwich deformation. The bottom skin in all the tests remains intact.

Leishmania major: Species specific delayed hypersensitivity reaction induced by exogenous secreted antigen in the guinea pig

The cellular response to Leishmania major ( L. major) is usually evaluated in vivo by the delayed-type-hypersensitivity (DTH) test using leishmanin. Leishmanin can give false-positive reactions in areas where there is a background of leishmaniasis. In a previous study, it was shown that a 56 kDa antigen purified from promastigote and culture supernatant of L. major induce strong DTH reactions in sensitized guinea pigs. In this study, the species-specificity of this antigen was further investigated. Three groups of guinea pigs were sensitized with L. major, L. tropica, and L. infantum and both flanks of sensitized animal were injected intradermally with purified 56 kDa antigen or soluble leishmania antigen (SLA). The extent of indurations were measured after 24, 48, and 72 h. In animals which were sensitized with three species of leishmania, only those immunized with L. major showed skin reactions to purified antigen by an increase in skin thickness. Since complex antigen mixtures such as SLA and leishmanin show cross-reactivity and can be non-specific, the result obtained here suggest that 56 kDa antigen may be a useful diagnostic tool for species specific diagnosis in field studies of leishmaniasis.

The effect of local anaesthetic cream (EMLA ®) applied with an occlusive dressing on skin thickness. Does it matter?

EMLA cream is used in plastic surgery as a topical anaesthetic to harvest split skin grafts. It has been observed that the skin appears pale and oedematous after the application of EMLA. The aim our study was to determine the effect of EMLA with an occlusive dressing on skin thickness using a high frequency ultrasound. Twenty volunteers took part in this study after approval from the ethics committee. An area of skin was marked on both thighs and the skin thickness of each, measured using ultrasound. EMLA with an occlusive dressing was applied to one thigh. This was removed after at least 2 h of application time but at different time points and skin thickness of each thigh measured again. Data was analysed using t-test and Pearson's correlation. Mean age in years +/- SD (range) was 36.1 +/- 12.1 (23 - 61). Male:female ratio was 8:12. Mean skin thickness +/- SEM increased from 1.86 +/- 0.055 mm prior to EMLA application to 1.96 +/- 0.051 mm post-EMLA application p= 0.02. There was a significant correlation between the increase in skin thickness and duration of application of EMLA cream (p = <0.001, R2 = 0.59). The results conclude that EMLA applied under an occlusive dressing has an effect on skin tissue thickness and any surgeon who harvests split skin grafts under EMLA should be aware of this. Further research is needed to compare laser treatments performed under local anaesthetic creams against general anaesthesia as an increase in skin thickness may affect the depth of laser penetration.

The Effect of Solar-Simulated Radiation on the Elicitation Phase of Contact Hypersensitivity does not Differ Between Controls and Patients with Polymorphic Light Eruption

It has been suggested that polymorphic light eruption (PLE) is characterized by a failure of ultraviolet radiation (UVR)-induced immunosuppression, resulting in a type-IV hypersensitivity response to photoinduced antigens. We measured the effect of solar-simulated radiation (SSR) on the elicitation phase of contact hypersensitivity to 2,4-dinitrochlorobenzene (DNCB), in ten PLE patients and 11 controls. Subjects were given a sensitizing dose of DNCB, and 3 wk later were exposed to 0.75 and 2 minimum erythema doses (MED) of SSR on the upper inner arm. Immediately and 24 h later these sites, and a non-irradiated control site, were challenged with DNCB. The resulting increase in skin thickness was measured with high-frequency ultrasound. Overall, 2 MED caused 17%-20% suppression of elicitation responses (compared with 93% suppression of sensitization reported previously), but the effect of SSR varied greatly between subjects, with some subjects showing potentiated responses, which may be of relevance to false-positive reactions in photopatch testing. In a repeated measures general linear model, SSR overall caused significant suppression of responses (p<0.001); there was less suppression in older subjects (p=0.009) but there was no significant difference between PLE patients and age-matched normal controls. These results contrast with our previous finding of a resistance to UVR-induced suppression of sensitization to DNCB in PLE. This difference may reflect the greater importance of Langerhans cells in the sensitization phase, and is consistent with the hypothesis that PLE arises from impaired suppression of Langerhans cell activation or migration.

Repeated Topical Challenge with Chemical Antigen Elicits Sustained Dermatitis in NC/Nga Mice in Specific-Pathogen-Free Condition

NC/Nga mice are known to develop skin lesions resembling to atopic dermatitis (AD) in conventional but not in specific-pathogen-free (SPF) condition. An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) increased skin thickness in C3H as well as NC/Nga mice in SPF environment, and the response was enlarged by repeating the challenge at weekly intervals. Although the skin reaction in C3H mice was ameliorated when the challenge was discontinued after the fifth application, the reaction in NC/Nga mice was sustained at least for 3 wk. Analyses of cytokine production by CD4+ cells from the draining lymph node proximal to the lesions revealed that, unlike C3H mice, NC/Nga mice fail to induce T helper 2 (Th2) cytokine interleukin-4 (IL-4), whereas the level of Th1 cytokine interferon-gamma in NC/Nga mice is equivalent to that of C3H mice. In addition, NC/Nga mice highly expressed IL-12, a cytokine-preventing formation of Th2 response, whereas C3H mice did not. Administration of anti-IL-12 antibody reduced duration of dermatitis in DNFB-treated NC/Nga mice. Taken together, our data suggest that IL-12 plays a role in the persistent skin reaction in NC/Nga mice. The action of IL-12 might be mediated by the decrease in IL-4 production.