GHRH expression plasmid improves osteoporosis and skin damage in aged mice.

The hormone secretion of GHRH-GH-IGF-1 axis in animals was decreased as aging. These hormones play an important role in maintaining bone mass and bone structure, and also affect the normal structure and function of the skin. We used plasmid-based technology to deliver growth hormone releasing hormone (GHRH) to elderly mice. In the current study, 80 and 120 µg/kg pVAX-GHRH plasmid expression plasmid were injected into old mice, the serum GHRH and insulin-like growth factor-1(IGF-1) content were increased within three weeks (P < 0.05). In the groups of 80 and 120 µg/kg plasmid, the content of procollagen type I N-terminal pro-peptide (PINP) in the serum was increased(P < 0.05), and the content of C-terminal telopeptides of type I collagen (CTX-1) in the serum was reduced significantly (P < 0.05). Furthermore, the expression of osteoprotegerin (OPG) and osteocalcin (OCN) in the femur also was increased(P < 0.05). The bone mineral density(BMD)、trabecular bone volume (BV/TV) and trabecular number(Tb.N) of mouse femur were increased significantly (P < 0.05) and trabecular separation(Tb.Sp) was decreased(P < 0.05). There were more trabecular bones in the bone marrow cavity and the trabecular bones are thicker in the groups of 80 and 120 µg/kg plasmid relative to control. The superoxide dismutase (SOD) content in the skin was increased(P < 0.05), and the malondialdehyde (MDA) content was reduced significantly (P < 0.05). Meanwhile, the skin moisture content also increased significantly(P < 0.05). Moreover, the expression of matrix metalloproteinase 3(MMP3) and matrix metalloproteinase 9(MMP9) was decreased in the skin(P < 0.05). The thickness of the dermis and epidermis of the skin had increased significantly(P < 0.05). Skin structure is more dense and complete in the two groups. These results indicate that 80 and 120 µg/kg plasmid-mediated GHRH supplementation can improve osteoporosis and skin aging in aged mice.

Flavonoids and saponins from Passiflora edulis f. edulis leaves (purple passion fruit) and its potential anti-inflammatory activity.

OBJECTIVES: The objective of this work was to evaluate the anti-inflammatory activity of the aqueous extract, fractions and major compounds, which are isolated and identified from Passiflora edulis f. edulis (purple passion fruit) leaves extract. METHODS: For the isolation of the major compounds, reversed-phase chromatography and normal phase countercurrent chromatography were used. The separation was followed by thin layer chromatography and HPLC-DAD-ELSD. One-dimensional and two-dimensional NMR and ESI-TOF-MS/MS were used for structural elucidation. The anti-inflammatory activity was evaluated on a TPA multiple dose model of skin chronic inflammation in mice. Additionally, myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity assays were performed as possible mechanisms of action studies. KEY FINDINGS AND CONCLUSIONS: The study of the butanolic fraction mainly showed the presence of saponins and flavonoids. Three minor flavonoids were detected; and three known saponins, cyclopassiflosides IX, XI and III were isolated and identified. This is the first unequivocal report of the presence of these compounds in P. edulis f. edulis leaves. The most favourable results of anti-inflammatory activity were obtained for the flavonoid-rich fraction. All the fractions and isolated compounds evaluated, presented high percentages of inhibition of nitric oxide synthase activity.

Risk factors for peristomal skin disorders associated with temporary ileostomy construction.

PURPOSE: Skin disorders are the most common stoma-related complications after temporary diverting loop ileostomy with proctectomy. The aim of the present study was to investigate risk factors for skin disorders associated with temporary ileostomy construction. METHODS: A total of 185 consecutive patients who underwent curative proctectomy with temporary diverting loop ileostomy for rectal malignancies at a single comprehensive cancer center between 2013 and 2018 were collected and analyzed. RESULTS: The most frequent stoma-related complications were skin disorders (n = 62, 33.5%), followed by mucocutaneous separation (n = 38, 20.5%) and high-output stoma (n = 34, 18.4%). Patients with skin disorders had a higher median body mass index (BMI; 22.4 vs. 21.3 kg/m2, P = 0.002) and lower stoma height (16 vs. 20 mm, P < 0.001) than those without skin disorders. According to a multivariable logistic regression analysis, independent predictors of skin disorders included overweight (median BMI ≥ 25 kg/m2 [odds ratio = 3.6, 95% confidence interval: 1.5-8.6], P = 0.004) and lower stomal height (median stoma height < 20 mm [odds ratio = 3.2, 95% confidence interval: 1.6-6.3], P < 0.001). CONCLUSION: Overweight and lower stoma height are correlated with the presence of skin disorders. Construction of a well-elevated stoma can reduce skin disorders associated with temporary ileostomy construction.

Long-term progression-free survival in a patient with advanced non-small-cell lung cancer treated with low-dose gefitinib and traditional herbal medicine: A case report.

RATIONALE: Gefitinib is a first-line palliative chemotherapy drug used to treat advanced non-small-cell lung cancer (NSCLC) in patients who have an epidermal growth factor receptor (EGFR) mutation. However, approximately two-thirds of NSCLC patients with EGFR-tyrosine kinase inhibitor experience dermatological toxicity. Cutaneous toxicity is usually not life threatening but can necessitate modification or discontinuation of medication in severe cases. In this case, despite a reduction in the dose of gefitinib due to side effects, combined treatment with modified Bojungikki-tang (BJKIT) increased progression-free survival (PFS) in an advanced NSCLC patient. PATIENT CONCERNS: An 83-year-old Asian woman presented with chief complaints of chronic cough, dyspnea, weight loss, and anorexia. DIAGNOSES: The patient was diagnosed with stage IV NSCLC (T2aN3M1), adenocarcinoma with metastasis to the lymph node, brain, and bone based on image scan and biopsy. An EGFR deletion was detected in exon 19. INTERVENTIONS: The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT). However, after 1 year of combination therapy, gefitinib was tapered down to once per week while modified BJIKT was maintained. OUTCOMES: A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months. LESSONS: Despite the reduction in gefitinib dose due to side effects, the combined treatment of gefitinib and the modified BJIKT has maintained a PFS of over 78 months, indicating that modified BJIKT enhanced the anti-cancer effect of gefitinib in a patient with advanced NSCLC harboring the EFGR mutation, and may have delayed acquired resistance, the main limitation on the efficacy of gefitinib. Further investigations including clinical trials are needed to confirm these effects.

Skin toxicity following radiotherapy in patients with breast carcinoma: is anthocyanin supplementation beneficial?

BACKGROUND: The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. OBJECTIVE: To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. METHODS: Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. RESULTS: 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. CONCLUSIONS: Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.

Dietary supplements in dermatology: A review of the evidence for zinc, biotin, vitamin D, nicotinamide, and Polypodium.

Dietary supplements are commonly recommended by dermatologists in the treatment of skin, hair, and nail disorders. This review of oral over-the-counter supplement use in dermatology summarizes current evidence for the use of zinc, biotin, vitamin D, nicotinamide, and Polypodium in the management of common dermatologic disorders. Evidence for the safety and efficacy of these supplements is limited. Very few large-scale randomized controlled trials exist for these over-the-counter supplements, particularly biotin and Polypodium. The lack of standardized dosing and standardized outcome measures makes comparison across existing studies challenging, and the lack of adverse events reporting in the majority of studies limits analysis of supplement safety. The most promising evidence exists for the use of nicotinamide in preventing nonmelanoma skin cancers. There is some evidence for the role of vitamin D in decreasing melanoma risk and progression in some individuals and for the photoprotective role of Polypodium, although additional high-quality studies are needed to determine appropriate dosing. Current evidence is insufficient to recommend the use of biotin or zinc supplements in dermatology. Large-scale randomized controlled trials investigating safety and efficacy are needed before widespread incorporation of these oral supplements into the general practice of dermatology.

Role of Vitamins in Skin Health: a Systematic Review.

PURPOSE OF REVIEW: Skin is the main defense organ of the human body against external insults (ultraviolet radiations, infections by pathogenic microorganisms, and mechanical and chemical stress). The integrity and functions of the skin barrier are supported by an adequate supply of micronutrients, such as several vitamins. The purpose of this review was to analyze all vitamin-related skin problems. RECENT FINDINGS: The World Health Organization has estimated that more than 2 billion people worldwide experience deficiencies in the intake of essential vitamins and minerals; the percentage of adults all over the world using daily vitamin supplements, for treatment or prevention of chronic disease, has increased very rapidly in recent years. In this review, 65 studies have been selected in order to examine the role of the main vitamins and their derivatives involved in maintaining the well-being of the skin and their use as prophylactic and therapeutic agents in the management of skin disorders.

Investigating barriers and challenges to the integrated management of neglected tropical skin diseases in an endemic setting in Nigeria.

BACKGROUND: There is a dearth of experience in and evidence for cost-effective integrated community-based management of skin neglected tropical diseases (NTDs). The objective of this study was to assess the knowledge, attitude and care-seeking practices including self-care with a view to introducing appropriate community-based interventions for skin NTDs in an endemic setting in Southern Nigeria. METHODS/PRINCIPAL FINDINGS: This exploratory study adopted a mixed-methods design consisting of cross-sectional surveys of community members and health workers using interviewer-administered questionnaires; and focus group discussions (FGDs) with community members, health care workers and patients with NTDs in Anambra State, Nigeria. The survey was completed by 353 community members (61.8% female) and 15 health care workers (100.0% female). A total of 52 individuals participated in six FGDs. Of the community members, 236 (66.9%) had heard or seen a case of leprosy; 324 (91.8%) and 131 (37.5%) had heard or seen a case of Buruli ulcer and lymphatic filariasis, respectively. Again, 213 (60.3%) of the respondents reported that the diseases were caused by witchcraft or curse. As regards prevention, 241 (68.3%) suggested avoiding handshake with affected persons. Up to 223 (63.2%) of respondents strongly agreed to the seriousness of skin NTDs in their community. Meanwhile, 272 (77.1%) of the respondents believed that the transmission of these skin NTDs can be prevented. Furthermore, 324 (91.7%) desired active community engagement for control of skin NTDs. Regarding community care seeking practices, 197 (55.8%) would first visit the health centre/hospital, followed by 91 (25.8%) traditional healer/herbalist and 35 (9.9%) pharmacy/patent medicine vendor if they develop a skin NTD. Overall, 332 (94.1%) of respondents expressed interest in being taught self-care practices for skin NTDs. Out of 15 healthcare workers, 13 (86.7%) were able to correctly diagnose two of these skin NTDs and 10 (66.7%) would encourage patients to practice self-care. Prominent themes in the FGDs were belief in witchcraft and herbal remedies; as well as the occurrence of physical, social and economic distress. CONCLUSIONS: Our study helped quantify the information gaps that need to be addressed in order to create demand for integrated skin NTDs services in an endemic setting in Nigeria. Individual, structural and socioeconomic challenges to access and delivery of services were identified. Community and health care workers' empowerment and engagement through outreach and regular training, respectively may alleviate these challenges.

Administration of Apple Polyphenol Supplements for Skin Conditions in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20-39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.

The role of diet in preventing photoaging and treating common skin conditions.

As interest in complementary and alternative medicine has grown, the relationship between diet and skin health has become an active area of research. Various supplements, plant derivatives, and antioxidants have gained attention as possible tools to prevent signs of aging and improve skin conditions. As such, knowledge of clinical trial data is important to counsel patients appropriately on risks and benefits of these complementary treatments and lifestyle modifications. Herein, we review the role of diet and supplements in preventing photoaging and treating common skin conditions.

Safety of a formulation containing chitosan microparticles with chamomile: blind controlled clinical trial.

OBJECTIVE: to evaluate the safety of a topical formulation containing chamomile microparticles coated with chitosan in the skin of healthy participants. METHOD: phase I blind, controlled, non-randomized, single-dose clinical trial with control for skin, base formulation, and formulation with microparticles. The variables analyzed were irritation and hydration by the Wilcoxon and Kruskall-Wallis tests. RESULTS: the study started with 35 participants with a mean age of 26.3 years. Of these, 30 (85.71%) were female, 29 (82.90%) were white skinned and 32 (91.40%) had no previous pathologies. One participant was removed from the study reporting erythema at the site of application, and four other participants for not attending the last evaluation. In the 30 participants who completed the study, the tested formulation did not cause erythema, peeling, burning, pruritus or pain; there was an improvement in cutaneous hydration in the site of application of the formulation with microparticles. In the evaluation of the barrier function, there was an increase in transepidermal water loss in all sites. CONCLUSION: the formulation with chamomile microparticles is safe for topical use, not causing irritation and improving skin hydration over four weeks of use. Its effects on barrier function need further investigation. No. RBR-3h78kz in the Brazilian Registry of Clinical Trials (ReBEC).

Oral exposure to the free amino acid glycine inhibits the acute allergic response in a model of cow's milk allergy in mice.

The conditionally essential amino acid glycine functions as inhibitory neurotransmitter in the mammalian central nervous system. Moreover, it has been shown to act as an anti-inflammatory compound in animal models of ischemic perfusion, post-operative inflammation, periodontal disease, arthritis and obesity. Glycine acts by binding to a glycine-gated chloride channel, which has been demonstrated on neurons and immune cells, including macrophages, polymorphonuclear neutrophils and lymphocytes. The present study aims to evaluate the effect of glycine on allergy development in a cow's milk allergy model. To this end, C3H/HeOuJ female mice were supplemented with glycine by oral gavage (50 or 100 mg/mouse) 4 hours prior to sensitization with cow's milk whey protein, using cholera toxin as adjuvant. Acute allergic skin responses and anaphylaxis were assessed after intradermal allergen challenge in the ears. Mouse mast cell protease-1 (mMCP-1) and whey specific IgE levels were detected in blood collected 30 minutes after an oral allergen challenge. Jejunum was dissected and evaluated for the presence of mMCP-1-positive cells by immunohistochemistry. Intake of glycine significantly inhibited allergy development in a concentration dependent manner as indicated by a reduction in; acute allergic skin response, anaphylaxis, serum mMCP-1 and serum levels of whey specific IgE. In addition, in-vitro experiments using rat basophilic leukemia cells (RBL), showed that free glycine inhibited cytokine release but not cellular degranulation. These findings support the hypothesis that the onset of cow's milk allergy is prevented by the oral intake of the amino acid glycine. An adequate intake of glycine might be important in the improvement of tolerance against whey allergy or protection against (whey-induced) allergy development.

Cosmetic and Therapeutic Applications of Fish Oil's Fatty Acids on the Skin.

Fish oil has been broadly reported as a potential supplement to ameliorate the severity of some skin disorders such as photoaging, skin cancer, allergy, dermatitis, cutaneous wounds, and melanogenesis. There has been increasing interest in the relationship of fish oil with skin protection and homeostasis, especially with respect to the omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). The other PUFAs, such as α-linolenic acid (ALA) and linoleic acid (LA), also show a beneficial effect on the skin. The major mechanisms of PUFAs for attenuating cutaneous inflammation are the competition with the inflammatory arachidonic acid and the inhibition of proinflammatory eicosanoid production. On the other hand, PUFAs in fish oil can be the regulators that affect the synthesis and activity of cytokines for promoting wound healing. A systemic review was conducted to demonstrate the association between fish oil supplementation and the benefits to the skin. The following describes the different cosmetic and therapeutic approaches using fatty acids derived from fish oil, especially ALA, LA, DHA, and EPA. This review summarizes the cutaneous application of fish oil and the related fatty acids in the cell-based, animal-based, and clinical models. The research data relating to fish oil treatment of skin disorders suggest a way forward for generating advances in cosmetic and dermatological uses.

Percutaneous Sensitization to Soybean Proteins Is Attenuated by Oral Tolerance.

Oral tolerance prevents allergic responses, but cutaneous exposure to food allergens predisposes individuals to food allergies. Soybean, a major allergenic food, is also an ingredient in various cosmetic products. However, it remains to be determined whether oral tolerance prevents percutaneous sensitization to soybean proteins in humans or animal models. In this study, BALB/c mice were divided into three groups; the SS group fed a soybean-containing diet, and the CS and control (C) groups fed a soybean-free diet. After being dorsally shaved, the CS and SS groups were epicutaneously exposed to a soybean extract while the control group was exposed to only the carrier. Specific IgE and IgG1 immunoglobulins secreted in response to the soybean proteins were measured using enzyme-linked immunosorbent assays. Exposure to the soybean extract elicited the secretion of IgE and IgG1 specific for Gly m 5 and Gly m 6, and trypsin inhibitor. Oral soybean consumption attenuated the secretion of all the soybean-specific IgEs and IgG1s, suggesting that percutaneous sensitization to soybean proteins is attenuated by oral tolerance.

Safety of a formulation containing chitosan microparticles with chamomile: blind controlled clinical trial / Segurança de uma formulação contendo micropartículas de quitosana com camomila: ensaio clínico, mascarado e controlado / Seguridad de una formulación conteniendo micropartículas de quitosano con manzanilla: ensayo clínico, enmascarado y controlado

ABSTRACT Objective: to evaluate the safety of a topical formulation containing chamomile microparticles coated with chitosan in the skin of healthy participants. Method: phase I blind, controlled, non-randomized, single-dose clinical trial with control for skin, base formulation, and formulation with microparticles. The variables analyzed were irritation and hydration by the Wilcoxon and Kruskall-Wallis tests. Results: the study started with 35 participants with a mean age of 26.3 years. Of these, 30 (85.71%) were female, 29 (82.90%) were white skinned and 32 (91.40%) had no previous pathologies. One participant was removed from the study reporting erythema at the site of application, and four other participants for not attending the last evaluation. In the 30 participants who completed the study, the tested formulation did not cause erythema, peeling, burning, pruritus or pain; there was an improvement in cutaneous hydration in the site of application of the formulation with microparticles. In the evaluation of the barrier function, there was an increase in transepidermal water loss in all sites. Conclusion: the formulation with chamomile microparticles is safe for topical use, not causing irritation and improving skin hydration over four weeks of use. Its effects on barrier function need further investigation. No. RBR-3h78kz in the Brazilian Registry of Clinical Trials (ReBEC).

RESUMO Objetivo: avaliar a segurança de uma formulação tópica, contendo micropartículas de camomila revestidas com quitosana, na pele de participantes saudáveis. Método: ensaio clínico fase I, mascarado, controlado, não aleatorizado, de dose única, com controles da pele, da base da formulação e da formulação com micropartículas. As variáveis analisadas foram irritação e hidratação por meio dos testes de Wilcoxon e Kruskall-Wallis. Resultados: iniciaram o estudo 35 participantes com idade média de 26,3 anos. Destes, 30 (85,71%) eram do sexo feminino, 29 (82,90%) brancos e 32 (91,40%) sem patologias prévias. Um participante foi descontinuado por referir eritema no local de aplicação e quatro por não comparecerem à última avaliação. Nos 30 participantes que finalizaram o estudo, a formulação teste não causou eritema, descamação, ardor, prurido ou dor; houve melhora na hidratação cutânea no local de aplicação da formulação com as micropartículas. Na avaliação da função barreira houve aumento da perda transepidérmica de água em todos os locais. Conclusão: a formulação com micropartículas de camomila é segura para o uso tópico, não provocando irritação e melhorando a hidratação cutânea ao longo de quatro semanas de uso. Seus efeitos na função barreira devem ser melhor estudados. N° RBR-3h78kz no Registro Brasileiro de Ensaios Clínicos (ReBEC).

RESUMEN Objetivo: evaluar la seguridad de una formulación tópica, conteniendo micropartículas de manzanilla revestidas con quitosano, en la piel de participantes sanos. Método: ensayo clínico fase I, enmascarado, controlado, no aleatorizado, de dosis única, con controles de la piel, de la base de la formulación y de la formulación con micropartículas. Las variables analizadas fueron irritación e hidratación por medio de los tests de Wilcoxon y Kruskall-Wallis. Resultados: iniciaron el estudio 35 participantes con edad media de 26,3 años. De esos, 30 (85,71%) eran del sexo femenino, 29 (82,90%) blancos y 32 (91,40%) sin patologías previas. Un participante fue descontinuado por referir eritema en el local de aplicación y cuatro por no comparecer a la última evaluación. En los 30 participantes que finalizaron el estudio, la formulación test no causó eritema, descamación, ardor, prurito o dolor; hubo mejora en la hidratación cutánea en el local de aplicación de la formulación con las micropartículas. En la evaluación de la función barrera hubo aumento de la pérdida transepidérmica de agua en todos los locales. Conclusión: la formulación con micropartículas de manzanilla es segura para el uso tópico, no provocando irritación y mejorando la hidratación cutánea a lo largo de cuatro semanas de uso. Sus efectos en la función barrera deben ser mejor estudiados. N° RBR-3h78kz en el Registro Brasilero de Ensayos Clínicos (ReBEC).

Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells.

BACKGROUND: Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity. METHODS: The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy). RESULTS: TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions. CONCLUSIONS: Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims Proposed Under European Community Regulation 1924/2006 in the Framework of Maintenance of Skin Function.

Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims.

Recovery Effects of Oral Administration of Glucosylceramide and Beet Extract on Skin Barrier Destruction by UVB in Hairless Mice.

Purified glucosylceramide from beet extract (beet GlcCer) and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB)-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC) ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.

The Potential of Triterpenoids from Loquat Leaves (Eriobotrya japonica) for Prevention and Treatment of Skin Disorder.

The leaves of loquat (Eriobotrya japonica) possess high medicinal value and have been used as traditional medicines. However, there are no evidence-based studies on the skin-care effects of E. japonica leaves. To explore new biological activities of E. japonica leaves against skin disorder and to gain a better understanding of the chemical components associated with bioactivities, we evaluated 18 triterpenoids from E. japonica leaves on anti-melanogenesis, anti-acne, anti-allergy and anti-aging activities. Our results revealed that eight compounds showed anti-melanogenesis activity, of which ursolic acid (1) and maslinic acid (7) were the most potent with the similar selective index to that of arbutin. Structure-activity relationship and possible mechanism of active compounds were proposed. Twelve compounds exhibited anti-acne effect; ursolic acid (1), maslinic acid (7), corosolic acid (8) and euscaphic acid (12) showed highest activities against P. acnes. Four compounds displayed anti-allergy and anti-inflammatory activity; 3-epicorosolic acid (9) and euscaphic acid (12) showed marked activity against ß-hexosaminidase release. Finally, ursolic acid (1), pomolic acid (10), colosolic acid (8) and its methylated derivative (6) exhibited the highest anti-aging activity by stimulating collagen and hyaluronic acid (HA) production. Our findings provide valuable evidence that E. japonica leaves have potential applications as ingredients of function foods or cosmetics for health benefits and a number of triterpenoids may play an important role in these bioactivities.