Physiological effects of appropriate washing on xerotic skin.

BACKGROUND: Daily skin care is important for treatment of skin diseases, but few studies have reported on appropriate washing methods. AIM: This study aimed to provide guidance on washing techniques and examine changes in skin condition after using the recommended washing technique and foaming-type skin cleanser in patients with atopic or asteatotic dermatitis. METHODS: An internet-based questionnaire survey on skin symptoms and cleaning methods was conducted. Further, a left-right comparative, nonrandomized trial was performed in 19 patients with asteatotic or atopic dermatitis and xerosis. Participants were instructed to wash with a cotton towel and their normal cleanser during Weeks 1-4 and with bare hands or a cotton towel and the recommended foaming-type cleanser during Weeks 5-8. RESULTS: The survey revealed that the degree of lathering differed depending on the cleaning tool. In the trial, scores for erythema, desquamation, and xerosis in the lower legs were significantly reduced after 4 weeks compared with scores at the start. Between Weeks 4 and 8, scores for erythema, xerosis, and pruritus in the inner forearm on the side washed with bare hands and scores for xerosis, pruritus, and excoriation on the side washed with a cotton towel were significantly reduced. A significant increase was noted in stratum corneum ceramide content on both left and right inner forearms, whereas a significant decrease was noted in stratum corneum thymus and activation-regulated chemokine level ratios in the lower legs on both sides. CONCLUSIONS: Xerotic skin disease symptoms can be improved using appropriate body washing methods.

Bioactive substances in the stratum corneum of the epidermis found as indicators of skin damage due to sun exposure.

BACKGROUND/PURPOSE: Although an inflammatory response upon acute injury caused by ultraviolet radiation (UV) can be observed immediately, the influence of long-term, repetitive low-dose UV exposure on the skin cannot be precisely perceived, making early detection of chronic damage difficult. This study investigated bioactive substances in the stratum corneum as a potential early and sensitive indicator of the influence of sun exposure on the skin using receiver operating characteristic (ROC) analysis. METHODS: Receiver operating characteristic analysis was performed to assess the responsiveness of cytokines [interleukin (IL)-1α, IL-1 receptor antagonist (IL-1ra), IL-10, tumor necrosis factor (TNF)-α], BCL2-associated protein X (Bax), Toll-like receptor (TLR)3, and TLR4 in the stratum corneum of healthy people exposed (dorsum of the hand) and unexposed (inner arm) to UV. Sunscreen was applied to patients with photodermatosis for 4 weeks to evaluate changes in IL-1ra/IL-1α, TNF-α, Bax, and TLR3 levels after sunscreen application, as these molecules exhibited high responsiveness to sun exposure according to ROC analysis. In addition, IL-1ra, IL-1α, and IL-10 levels were quantified by enzyme-linked immunosorbent assay, and TNF-α, Bax, TLR3, and TLR4 levels were semi-quantitatively assessed by immunocytochemistry. RESULTS: Receiver operating characteristic analysis identified IL-1ra/IL-1α, TNF-α, Bax, and TLR3 in the stratum corneum as highly responsive to sun exposure. Moreover, in participants, including patients with photodermatosis, IL-1ra/IL-1α, TNF-α, and Bax levels decreased significantly after sunscreen application. CONCLUSION: The results revealed that IL-1ra/IL-1α, TNF-α, and Bax in the stratum corneum represent sensitive indicators of the influence of sun exposure on the skin.

Optimal application method of a moisturizer on the basis of skin physiological functions.

BACKGROUND: Clinical studies have clarified the usefulness of moisturizers for dry skin diseases. However, few reports exist on the appropriate application of moisturizers with respect to the skin physiological functions. AIMS: To clarify the optimal moisturizer application method on the basis of skin physiological functions. METHODS: This study investigated the appropriate time, dose, and frequency of moisturizer application from the perspective of skin physiology. In healthy subjects, the stratum corneum water content (SCW) was compared between different moisturizer application times (immediately [≤5 min] and 90 min after bathing), doses (0.5, 1.0, and 2.0 mg/cm2 ), and frequencies (once and twice daily). Thereafter, patients with dry skin were treated with the moisturizer once or twice daily for 8 weeks at the time, and application dose was determined to be optimal for the healthy subjects; the moisturizing effect was evaluated based on the SCW, trypsin activity, and desmoglein 1 localization score in the stratum corneum. RESULTS: In healthy subjects, compared to at control sites, the SCW was significantly higher at sites treated with the moisturizer immediately after bathing, with 1.0 and 2.0 mg/cm2 of the moisturizer, and with once- and twice-daily applications. In patients with dry skin, the SCW was significantly higher compared to control sites and the desmoglein 1 localization score was significantly lower after 8 weeks only when the moisturizer was applied twice daily. CONCLUSIONS: Moisturizer application of ≥1.0 mg/cm2 twice daily (immediately after bathing at night and in the morning) had a moisturizing effect, as verified from the skin physiological functions.

Effect of Vitamin-Containing Amino Acid Supplements on Menopausal Symptoms and Age-Related Skin Changes: A Randomised, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Women aged ≥ 45 years are known to experience various menopausal symptoms due to reduced oestrogen levels. Changes associated with cutaneous ageing, such as wrinkles and sagging, are also prominent in women in this age group. Numerous studies have evaluated the usefulness of individual basic nutrients and essential components, such as amino acids and vitamins, in menopausal women. The aim of this study was to comprehensively assess the effects of supplements containing amino acid and vitamin combinations on menopausal symptoms and age-related changes in the skin. METHODS: This is a randomised, placebo-controlled study on the effects of a supplement containing three types of amino acids [leucine, glutamine and arginine (LGA)] and 11 types of vitamins in 37 middle-aged women. The participants ingested either the test substance or a placebo twice daily for 8 consecutive weeks, at the end of which time the efficacy and safety of the test substance were assessed based on subjective symptoms of fatigue, Simplified Menopausal Index (SMI) score, the grade and number of wrinkles at the corners of the eyes, results of an analysis of the stratum corneum of the cheek and blood test results. RESULTS: None of the participants experienced adverse events, and all items assessed in our survey of subjective symptoms of fatigue showed a significant decrease in the test substance group (LGA group). Additionally, the SMI score of the LGA group was significantly lower than that of the placebo group. The LGA group showed significant improvement in the grade of the wrinkles in the corners of the eyes and the number of wrinkles, and the stratum corneum cell area declined significantly in the LGA group compared to the placebo group at the end of the study. CONCLUSION: These results indicate that the vitamin-containing amino acid supplement improved menopausal symptoms and age-related changes in the skin (wrinkles). TRIAL REGISTRATION: UMIN000029830.

Filaggrin-gene mutation has minimal effect on the disease severity in the lesions of atopic dermatitis.

Loss-of-function mutations of filaggrin (FLG) gene (FLG) are the strongest known genetic risk factor for atopic dermatitis (AD). It is still debatable how FLG gene mutations and the resulting abnormal amount of FLG protein contribute to skin barrier function and symptoms of AD. In this study, we examined the effects of loss-of-function mutations of FLG gene on the severity of skin lesions and skin barrier function in 55 patients with AD by evaluating eight patients with AD with FLG gene mutations and 47 patients with AD without mutations. The results showed that the FLG gene mutation did not affect the duration of AD, severity of AD, degree of local inflammatory symptoms, skin water content and trans-epidermal water loss of the lesions. Next, in these eight mutation carriers and the 47 non-carriers, stratum corneum was collected from the three site of skin lesions using tape-stripping method, and the amounts of FLG protein and total amino acid contained in the stratum corneum was measured to investigate the effect of the FLG gene mutation on the amount of FLG gene product in the local lesion. FLG abnormalities had little effect on FLG protein and total amino acid content in the stratum corneum in the lesional skin. The amount of the FLG products, especially amino acids derived from FLG, in the stratum corneum of AD lesional skin is influenced by development of dermatitis. The results obtained from this study supports that the activation of Th2-dominant inflammatory cells, together with FLG abnormality, plays a role in suppressing the production of FLG in skin lesions.

Novel petrolatum-based ointment that is highly moisturizing and has superior usability with increased adherence in patients with facial dry skin.

BACKGROUND: Petrolatum is often used to suppress water evaporation from the skin surface. However, its stickiness, shininess, and other factors make it inconvenient for continuous use. OBJECTIVE: To compare the effectiveness and usability between a newly developed petrolatum-based ointment (NOV® II Moisture Balm) and white petrolatum. METHODS: Twenty-nine subjects with atopic dermatitis or xeroderma with symptoms of dry skin applied NOV® II Moisture Balm on the right sides of the face and white petrolatum on the left side, respectively, for 8-12 weeks. The skin conditions (erythema, exudate/crusting, dryness, and itch) were scored, stratum corneum water content and transepidermal water loss (TEWL) were measured, and the free amino acid and thymic stromal lymphopoietin (TSLP) levels in the stratum corneum were analyzed before and end of the trial. RESULTS: Dryness, exudate/crusting, and TEWL decreased significantly on both the white petrolatum and the NOV® II Moisture Balm sides, while stratum corneum water content and the free amino acid levels in the stratum corneum increased significantly. On the NOV® II Moisture Balm side, erythema and the TSLP levels decreased significantly. In a questionnaire on usability, the subjects felt NOV® II Moisture Balm spread better and were less sticky and shiny than white petrolatum, and more subjects wanted to continue using NOV® II Moisture Balm. CONCLUSIONS: NOV® II Moisture Balm was equivalent to white petrolatum in moisturizing and improving the physiologic functions of the skin, but had superior usability.

A Case of a Pregnant Woman with Thrombosis in an Artificial Aortic Valve Resulting in Severe Cerebral Hemorrhage in the Newborn.

Many patients, after artificial valve replacement surgery, receive warfarin anticoagulant therapy. However, it has been reported that warfarin administration during pregnancy can cause fetal teratogenicity. With reference to this case, we will discuss how warfarin administration in mid-pregnancy caused severe cerebral hemorrhage in the newborn child. The 36-year-old patient in this case underwent aortic valve replacement surgery when she was 11 years old; this requires the continued use of warfarin after surgery. Although she was advised otherwise, the patient became pregnant. The warfarin treatment was discontinued at 5 weeks of gestation and she began self-injection of heparin; however, her health quickly deteriorated requiring an emergency, warfarin treatment. On gestation week 21, she was admitted to our hospital with a high likelihood of a spontaneous abortion. A week later, transesophageal ultrasonography revealed a thrombus in the patient's aortic valve. Because of this finding, we re-started warfarin administration. At 32 weeks of gestation, cardiotocography showed decreased fetal heart rate; thus, an emergency Cesarean section was performed. A baby was delivered, weighing 1,702 g with an Apgar Score of 1 at 1 minute and 4 at 5 minutes. Cranial computed tomography of the infant showed bilateral intraventricular hemorrhage and ventricular dilation. In order to protect the mother and prevent hemorrhage in the newborn, it is recommended that a continuous heparin infusion should be administered to the pregnant woman after the 36th week of gestation. Regarding the impact on the infant, it is considered that continuous intravenous administration of heparin is safer during the third trimester of pregnancy. However, administration of heparin alone makes the preventive effect of thrombosis uncertain. When warfarin is administered in pregnancy, pregnancy management should be performed bearing the risk of fetal cerebral hemorrhage in mind.

Probing Single Pt Atoms in Complex Intermetallic Al13Fe4.

The atomic structure of a 0.2 atom % Pt-doped complex metallic alloy, monoclinic Al13Fe4, was investigated using a single crystal prepared by the Czochralski method. High-angle annular dark-field scanning transmission electron microscopy showed that the Pt atoms were dispersed as single atoms and substituted at Fe sites in Al13Fe4. Single-crystal X-ray structural analysis revealed that the Pt atoms preferentially substitute at Fe(1). Unlike those that have been reported, Pt single atoms in the surface layers showed lower activity and selectivity than those of Al2Pt and bulk Pt for propyne hydrogenation, indicating that the active state of a given single-atom Pt site is strongly dominated by the bonding to surrounding Al atoms.

Physiological and microbiological verification of the benefit of hair washing in patients with skin conditions of the scalp.

BACKGROUND: It is unclear whether hair washing is effective against scalp eruption and pruritus caused by seborrheic dermatitis or psoriasis vulgaris. AIMS: To assess whether a proper hair-washing regimen, including the use of antibacterial shampoo, can ameliorate scalp eruption symptoms and alter the composition of the scalp microflora. METHODS: Eighteen patients with seborrheic dermatitis or psoriasis vulgaris scalp eruptions were instructed in proper techniques of daily hair washing, rinsing, and shampooing, which they underwent for 12 weeks. They used control shampoo in weeks 1-4 and 9-12, and an antibacterial shampoo during weeks 5-8. At the start of the test period and at weeks 4, 8, and 12, we assessed scalp symptoms (erythema, scaling/desquamation, dryness, itchiness, and scratching scars); microbial DNA levels from lesion and nonlesion areas; and levels of interleukin (IL)-1α, IL-1ra, and total protein in the scalp's horny layer. RESULTS: Compared to baseline values, scaling/desquamation and itchiness improved significantly at weeks 8 and 12. Other observed skin symptoms also improved over time. Malassezia colonization levels in lesion and nonlesion areas decreased gradually; the decrease was significant at week 8 in lesion areas and at weeks 4 and 8 in nonlesion areas. Bacterial colonization levels also decreased gradually, achieving significance in lesion areas at week 4. Gradual decreases in IL-1ra/IL-1α level showed statistical significance at weeks 4 and 12, while the protein quantity significantly decreased at week 12. CONCLUSION: Proper hair washing improved scalp condition symptoms, and possibly the underlying etiology.

Long-term disease-free survival after radical local excision of low-grade myofibroblastic sarcoma of the vulva.

•A second case of low-grade myofibroblastic sarcoma of the vulva.•Six-year follow-up with no evidence of disease after radical local excision.•Adequate margin resection is important.

Effect of sequential application of topical adapalene and clindamycin phosphate in the treatment of Japanese patients with acne vulgaris.

The efficacy of combined therapy with a retinoid and antibiotic for Japanese patients with acne vulgaris remains to be established. Further, maintenance strategies limiting the use of topical retinoids must be identified. The objectives of this study are to determine the efficacy of sequential application of topical adapalene and clindamycin phosphate and to assess the impact of this regimen on patients' quality of life. Sixty-six patients were recruited. The regimen comprised two phases. For the 4-week initial treatment, 1% clindamycin phosphate gel was applied twice daily and 0.1% adapalene gel, once. In the 4-week maintenance phase, patients were randomly assigned to the OD group (adapalene applied once daily) or the TW group (adapalene applied once daily on 2 days per week). The acne severity score, lesion counts, microcomedone count, and sebum amount were measured. Quality of life (QOL) was assessed using Skindex-16. All parameters improved significantly by week 4 of initial treatment. No statistically significant differences were found in the improvement of clinical findings between the groups. All QOL scores improved significantly and did not significantly differ between the groups. Our regimen may enable clinical control of acne in Japanese patients and improve their QOL. For limiting retinoid use, weekly application of adapalene during maintenance is suitable.

Combination effects of cosmetic moisturisers in the topical treatment of acne vulgaris.

Cosmetic moisturisers were applied to one side of the face of 18 male Japanese patients with acne vulgaris who were treated with a topical administration of adapalene and clindamycin phosphate gels. We assessed the alleviating effect of the moisturisers on the side effects of the treatment. The severity of acne and the number of inflammatory and non-inflammatory lesions were measured at 0, 2, and 4 weeks. The water content in the stratum corneum and transepidermal water loss were measured by comparing the moisturiser-treated and untreated sides of the face. The sensation of skin dryness and irritation on both sides of the face were assessed by the subjects. We observed that the use of moisturisers did not impact the efficacy of the standard topical treatment and they significantly improved the water content in the stratum corneum and the sensation of dryness. These results suggested that the use of moisturisers in combination with the standard topical treatment may improve adherence to therapy by alleviating the sensation of dryness.

Simultaneous noncontact topography and electrochemical imaging by SECM/SICM featuring ion current feedback regulation.

We described a hybrid system of scanning electrochemical microscopy (SECM) and scanning ion conductance microscopy (SICM) with ion current feedback nanopositioning control for simultaneous imaging of noncontact topography and spatial distribution of electrochemical species. A nanopipette/nanoring electrode probe provided submicrometer resolution of the electrochemical measurement on surfaces with complex topology. The SECM/SICM probe had an aperture radius of 220 nm. The inner and outer radii of the SECM Au nanoring electrode were 330 and 550 nm, respectively. Characterization of the probe was performed with scanning electron microscopy (SEM), cyclic voltammetry (CV), and approach curve measurements. SECM/SICM was applied to simultaneous imaging of topography and electrochemical responses of enzymes (horse radish peroxidase (HRP) and glucose oxidase (GOD)) and single live cells (A6 cells, superior cervical ganglion (SCG) cells, and cardiac myocytes). The measurements revealed the distribution of activity of the enzyme spots on uneven surfaces with submicrometer resolution. SECM/SICM acquired high resolution topographic images of cells together with the map of electrochemical signals. This combined technique was also applied to the evaluation of the permeation property of electroactive species through cellular membranes.

Topographic imaging of convoluted surface of live cells by scanning ion conductance microscopy in a standing approach mode.

Scanning ion conductance microscopy (SICM) using a nanopipette as a probe and ionic current as a feedback signal was introduced as a novel technique to study live cells in a physiological environment. To avoid contact between the pipette tip and cells during the conventional lateral scanning mode, we adopted a standing approach (STA) mode in which the probe was moved vertically to first approach and then retracted from the cell surface at each measurement point on an XY plane. The STA mode ensured non-contact imaging of the topography of live cells and for a wide range of uneven substrates (500 x 300 microm to 5 x 5 microm). We also used a field-programmable gate array (FPGA) board to enhance feedback distance regulation. FPGA dramatically increased the feedback speed and decreased the imaging time (450 s per image) with enhanced accuracy and quality of live cell images. To evaluate the potential of the STA mode for SICM, we carried out imaging of a convoluted surface of live cell in various scan ranges and estimated the spatial resolutions of these images.

Transfer profile of intramuscularly administered tetrodotoxin to non-toxic cultured specimens of the pufferfish Takifugu rubripes.

Tetrodotoxin (TTX) was intramuscularly administered to non-toxic cultured specimens of the pufferfish Takifugu rubripes to investigate TTX transfer/accumulation profiles in the pufferfish body. In two groups of test fish administered either 50MU/individual of TTX standard (purified TTX; PTTX) or crude extract of toxic pufferfish ovary (crude TTX; CTTX), TTX rapidly transferred from the muscle via the blood to other organs. The toxin transfer profiles differed between groups, however, from 4 to 72h. In the PTTX group, little TTX was retained in the liver, and most (>96%) of the toxin remaining in the body transferred/accumulated in the skin after 12h, whereas in the CTTX group, a considerable amount of toxin (15%-23% of the administered toxin or 28%-58% of the remaining toxin) was transferred/retained in the liver for up to 24h, despite the fact that 89% of the remaining toxin transferred/accumulated in the skin at the end of rearing period (168h). The total amount of toxin remaining in the entire body at 1-4h was approximately 60% of the administered toxin in both groups, which decreased at 8-12h, and then increased again to approximately 60%-80% at 24-168h. Immunohistochemical observation revealed that the toxin accumulated in the skin was localized at the basal cells of the epidermal layer.