Effects of Oral Administration of CoenzymeQ10 to Nonenal in Skin Gas of Elderly Women / 日本補完代替医療学会誌

To evaluate the impact of coenzyme Q10 (CoQ10) intake on body odor, two studies that focused on 2-nonenal contained in the gases emanated from the skin were conducted. The first study targeted 20 healthy women aged 65–74 years in a placebo-controlled cross-comparison study. Subjects were divided into two groups using blood CoQ10 concentration as an index, with ubiquinol (QH) or placebos administered every 4 weeks (5-week washout). On measuring concentrations of CoQ10 in blood and 2-nonenal in skin gas before and after continuous use, CoQ10 level of QH intake group increased significantly, whereas 2-nonenal level reduced significantly. In the second study, 24 healthy women aged 65–74 years were divided into four groups. QH, ubiquinone, vitamin E and placebos were administered in 4 weeks, and each concentrations of 2-nonenal in skin gas were measured. QH and ubiquinone reduced 2-nonenal in skin gas; however, changes in vitamin E were not observed. Therefore, CoQ10 intake reduced 2-nonenal emanation from the body.

A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis

Staphylococcus aureus (SA) is usually present not only in the skin lesions of atopic dermatitis (AD) but also in the atopic dry skin. SA discharges various toxins and enzymes that injure the skin, results in activation of epidermal keratinocytes, which produce and release IL-18. IL-18 that induces the super Th1 cells secreting IFN-gamma and IL-13 is supposed to be involved in development of AD and its pathogenesis. Indeed, the number of SA colonies on the skin surface and the serum IL-18 levels in patients with AD significantly correlated with the skin scores of AD lesions. Also, there is strong positive correlation between the skin scores and serum IL-18 levels in DS-Nh mice (P<0.0001, r=0.64), which develop considerable AD-like legions when they are housed under conventional conditions, but develop skin legions with less severity and less frequency under specific pathogens free (SPF) conditions. Therefore, they are well-known as model mice of AD, in which SA is presumed to be critical factor for the development of AD lesions. Also, theses DS-Nh mice pretreated with Cy developed more remarkable AD-like lesions in comparison with non-treated ones. The levels of INF-r and IL-13 in the supernatants of the lymph node cell cultures stimulated with staphylococcal enterotoxin B (SEB) or ConA were increased in the Cy-treated mice, although the serum levels of total IgE were not. In this experiment, we revealed that Cy-treated mice, to which CD25 +CD4 + reguratory T cells taken from non-treated ones had been transferred, developed the AD-like legions with less severity and less number of SA colonies on the skin surface. Therefore, it is presumed that CD25 +CD4 + reguratory T cells might be involved in the suppression of super Th1 cells which are induced by IL-18 and are involved in the development of AD-like lesions rather than IgE production. The efficient induction of CD25 +CD4 + reguratory T cells is expected for the new type of treatment of AD. We also found that farnesol (F) and xylitol (X) synergistically inhibited biofilm formation by SA, and indeed the ratio of SA in total bacteria at sites to which the FX cream containing F and X had been applied was significantly decreased 1 week later, accompanied with improvement of AD, when compared with that before application and at placebo sites. Therefore, the FX cream is a useful skin-care agent for atopic dry skin colonized by SA. The nerve growth factor (NGF) in the horny layer (the horn NGF) of skin lesions on the cubital fossa was collected by tape stripping and measured using ELISA in AD patients before and after 2 and 4 weeks treatments. Simultaneously, the itch and eruptions on the whole body and on the lesions, in which the horn NGF was measured, were recorded, and also the peripheral blood eosinophil count, serum LDH level and serum total IgE level were examined. The level of NGF was significantly higher in AD patients than in healthy controls, correlated with the severity of itch, erythema, scale/xerosis, the eosinophil count and LDH level, and also significantly decreased after treatments with olopatadine and/or steroid ointment for 2 and 4 weeks. Therefore, the measurement of the NGF by this harmless method seems to be useful to assess the severity of AD and the therapeutic effects on AD. In AD patients, C-fiber in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. We administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD, and investigated the effect of Sema3A on the skin lesions and their itch. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in the epidermal thickness, the density of invasive nerve fibers in the epidermis, inflammatory infiltrate including mast cells and CD4 +T cells, and the production of IL-4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch cycle likely contributes to the improvement of the AD-like lesions, Sema3A is expected to become a promising treatment of patients with refractory AD.

A novel method to control the balance of skin microflora. Part 1. Attack on biofilm of Staphylococcus aureus without antibiotics.

BACKGROUND: Staphylococcus aureus (SA) is usually present in atopic dry skin, and not only in regions seriously affected by atopic dermatitis. SA discharges various toxins and enzymes that injure the skin, and forms a biofilm from fibrin fiber and glycocalyx; the biofilm is important for adhesion of SA to the skin and for resistance to anti-microbial agents. Even highly effective moisturizers do not work perfectly on atopic dry skin. Staphylococcus epidermidis (SE) is a major constituent of skin microflora on healthy human skin, and provides protection against the growth of pathogenic bacteria. OBJECTIVES: Since treatment with anti-microbials may lead to re-growth of SA, which grows faster than other Staphylococci and often shows antibiotic resistance, we searched for novel approaches to control the skin-microfloral balance without using conventional anti-microbials. METHOD: Biofilm formation by SA in vitro was observed in detail using scanning electron microscopy. Approximately 500 substances were screened for a selective effect on SA growth and SA biofilm. RESULTS: We found that xylitol inhibited the formation of glycocalyx, and farnesol dissolved fibrin fibers. Farnesol suppressed the growth of only SA, and did not affect that of SE. Xylitol and farnesol synergistically inhibited biofilm formation by SA. CONCLUSION: Xylitol and farnesol have potential for controlling the skin-microfloral balance because of their selective effects and inhibition of biofilm formation. They might provide a useful and safe method to care for skin colonized by SA, without using antibiotics.

A novel method to control the balance of skin microflora Part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin.

BACKGROUND: It is recognized that colonization by Staphylococcus aureus (SA) on the skin is one of the factors that can worsen atopic dermatitis (AD). Antibiotics and germicides are not the best choice to remove bacteria from the skin of AD patients, because of problems of irritation to the skin and bacterial resistance. We therefore turned our attention to the biofilm of SA with the aim of removing only SA from the skin surface of AD patients. We found that xylitol (X) and farnesol (F) synergistically inhibited biofilm formation by SA and dissolved biofilm formed in vivo (Part 1). OBJECTIVE: To test whether application of AD for 1 week with FX cream can reduce SA without affecting Staphylococcus epidermidis. METHODS: A randomized, double-blind, placebo-controlled right-and-left comparison study was performed. The arms of 17 patients with dry-type AD were applied with skin-care cream including/or not including a 0.02% F and 5% X combination for 1 week. The clinical response, biophysical assessment of the skin surface and counts of skin microflora were recorded before and after 1 week of therapy. RESULTS: The ratio of SA in total bacteria at sites to which FX cream had been applied was significantly decreased after 1 week (P = 0.007), compared with before application and with placebo sites (P = 0.045). The mean skin conductance (a parameter indicating the state of hydration of the skin surface) of FX cream sites was increased significantly compared with the conductance before application (P = 0.0001) and at placebo sites (P = 0.002). CONCLUSION: This study provides evidence supporting the idea that cream containing F and X is a useful skin-care agent for atopic dry skin colonized by SA.