The Connection between Urinary Equol Levels and the Prevalence of Atopic Dermatitis.

BACKGROUND: Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy isoflavones and equol levels in atopic dermatitis remain uninvestigated. OBJECTIVE: The aim of this study is to compare the levels of urinary daidzein, genistein, and equol between atopic dermatitis patients and normal subjects and to examine the correlation between equol concentration and the severity of clinical symptoms. METHODS: A cross-sectional study was conducted at Akita University Hospital and Aso Iizuka Hospital in Japan. Fifty patients with confirmed atopic dermatitis diagnosis and 67 healthy controls were recruited. Daidzein, genistein, and equol in urine were measured by using a high-performance liquid chromatography-mass spectrometry system. RESULTS: Urinary equol levels were significantly lower in the atopic dermatitis patients than in the healthy controls (p = 0.002). The difference was particularly noticeable in young people (6-19 years, p < 0.001). No correlations were found between urinary equol levels and the severity of clinical symptoms and laboratory data in the atopic dermatitis patients. CONCLUSION: Equol levels in childhood might be involved in the development of atopic dermatitis.

Early pathology in venom-induced consumption coagulopathy by Rhabdophis tigrinus (Yamakagashi snake) envenomation.

Objective:Rhabdophis tigrinus (Yamakagashi in Japanese) is a venomous non-front-fanged colubroid snake capable of inflicting envenoming with life-threatening defibrinating coagulopathy. However, because of the uncommon incidence of bites and tendency for late development of symptoms/signs, the early effects of the venom on the coagulation system are poorly known. Case report: We describe a boy bitten by a wild R. tigrinus and report his clinical course starting at 30 min after the bite. Results: At 30 min after envenomation, only the thrombin-antithrombin complex (TAT) level was elevated. At 90 min after envenomation, laboratory data revealed a prolonged activated partial thromboplastin time (APTT) and increased prothrombin time international normalized ratio (PT-INR) with elevated fibrinogen degeneration product (FDP). At 5.5 h after envenomation, APTT and PT-INR increased beyond a measurable range, and fibrinogen levels dropped below the detection limit. We administered recombinant human soluble thrombomodulin and antivenom prepared against R. tigrinus antivenom. Venom-induced consumption coagulopathy (VICC), which is sometimes reported as disseminated intravascular coagulation (DIC), subsequently improved rapidly. Discussion: We found that TAT is the earliest marker to detect R. tigrinus envenomation and subsequent VICC occurrence. Although rTM was effective in this case, further studies are necessary to prove its safety and efficacy.

Measurement of trihydroxy-linoleic acids in stratum corneum by tape-stripping: Possible biomarker of barrier function in atopic dermatitis.

Epidermal ceramides are indispensable lipids that maintain the functions of the stratum corneum. Esterified omega-hydroxyacyl-sphingosine (EOS) ceramide with a linoleate moiety is one of the most important ceramide species for forming cornified lipid envelopes. This linoleate moiety is eventually metabolized to trihydroxy-linoleic acid (triol, 9,10,13-trihydroxy-11E-octadecenoic acid). Thus, we assumed that a decrease of triols might reflect skin barrier dysfunction. Against this background, the purposes of this study were to measure the triols by a simple tape-stripping method and to determine the correlation between the amount of triols and transepidermal water loss (TEWL) as an indicator of barrier dysfunction in atopic dermatitis patients. Twenty Japanese subjects with normal skin and 20 atopic dermatitis patients were enrolled in this study. TEWL was measured and triols of the stratum corneum were analyzed by tape-stripping. The results showed for the first time that triols in the stratum corneum could be simply measured using the tape-stripping method. The triol levels in atopic dermatitis patients were much higher than those in healthy subjects. Moreover, the triol levels correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis. The results suggest that the assaying of triol levels via non-invasive tape-stripping could be beneficial for monitoring barrier function in atopic dermatitis.

Clinical Condition and Management of 114 Mamushi (Gloydius blomhoffii) Bites in a General Hospital in Japan.

Objective Mamushi (Gloydius blomhoffii) snakebite is the most common type of snake injury in Japan and is also seen in China and Korea. Although the components of Mamushi venom have been investigated, epidemiological and clinical descriptions still remain limited in the English literature. The aim of this study was to review the clinical features and management of patients with injuries related to Mamushi snakebites. Methods We conducted a retrospective examination of 114 Mamushi snakebite cases encountered at a general hospital in Japan from January 2004 to November 2016. Data were collected from the medical records. Results We found that Mamushi snakebites commonly occurred during summer and the daytime, with elderly men typically being affected. The symptom grade at initial consultation was significantly worse in the walk-in group than in the ambulance admission group, probably due to treatment delay. The number of fangs that pierced the skin was not related to the severity of the symptoms. The group treated with a tourniquet more frequently exhibited exacerbation of symptoms than those that received other treatments (p<0.001). Conclusion The delay between patients being bitten and arriving at hospital as well as the number of fangs that pierced the skin did not affect the duration of hospitalization; however, proximal tourniquation should be avoided in such cases, as significant exacerbation of local symptoms was observed when this procedure was applied.

Localization of S100A2, S100A4, S100A6, S100A7, and S100P in the human hair follicle.

The hair follicle is a highly differentiated structure. In this study, we examined immunohistological localization of S100A2, S100A4, S100A6, S100A7, and S100P using specific monoclonal antibodies. S100A2 was strongly expressed in the entire outer-root sheath (ORS), but more weakly in cuticle and medulla in the bulb. S100A6, S100A7, and S100P were expressed in the innermost cells of ORS. The cuticular area was weakly positive for S100A2, S100A6, S100A7, and S100P. S100A4 was expressed in dendritic Langerhans cells and melanocytes. Sebaceous cells were variably immunopositive for S100A2, S100A6, and S100A7. A subset of dermal papilla cells expressed S100A4 and S100A6. None of the antibodies labeled the inner-root sheath. The distinct spatiostructural distributions of the S100 family proteins suggest that each protein is differentially involved in the physiological function of normal hair follicles.

Localization of S100A2, S100A4, S100A6, S100A7, and S100P in the human hair follicle.

The hair follicle is a highly differentiated structure. In this study, we examined immunohistological localization of S100A2, S100A4, S100A6, S100A7, and S100P using specific monoclonal antibodies. S100A2 was strongly expressed in the entire outer-root sheath (ORS), but more weakly in cuticle and medulla in the bulb. S100A6, S100A7, and S100P were expressed in the innermost cells of ORS. The cuticular area was weakly positive for S100A2, S100A6, S100A7, and S100P. S100A4 was expressed in dendritic Langerhans cells and melanocytes. Sebaceous cells were variably immunopositive for S100A2, S100A6, and S100A7. A subset of dermal papilla cells expressed S100A4 and S100A6. None of the antibodies labeled the inner-root sheath. The distinct spatiostructural distributions of the S100 family proteins suggest that each protein is differentially involved in the physiological function of normal hair follicles.

Reduction of serum TARC levels in atopic dermatitis by topical anti-inflammatory treatments.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) levels are associated with the disease activity of patients with atopic dermatitis (AD) and sensitively reflect short-term changes in skin conditions. The main treatment for AD is topical agent application. OBJECTIVE: This study investigated the relationship between serum TARC levels and the dosage of topical agents, including corticosteroids and/or tacrolimus, in patients with AD. METHODS: The serum TARC levels of 56 AD patients and the amounts of topical agents prescribed to them were investigated retrospectively. The weekly reduction in serum TARC levels and weekly dosage of topical agents among AD patients were compared and their associations were evaluated. RESULTS: The dosage of topical agents was closely related to serum TARC levels. One gram of strong rank steroid or the equivalent amount of steroid/tacrolimus is required to reduce serum TARC levels by 9.94 pg/mL weekly in moderate to severe AD patients. Higher initial TARC levels require more topical agent, which results in a more rapid decrease in TARC levels. The serum TARC levels and eosinophil numbers in peripheral blood are significantly correlated. CONCLUSION: Serum TARC level improvement and topical agent dosage are strongly correlated. TARC and eosinophil numbers are significantly correlated, but the wider range of TARC levels seems to be clinically more useful for monitoring AD severity. The serum TARC level is a very sensitive biomarker for monitoring the severity and treatment response in AD.

Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis.

BACKGROUND: S100 proteins belong to a family of calcium-binding proteins that regulate cell proliferation and differentiation. Despite our growing knowledge about the biology of S100 proteins in some human cancers, little is known about the expression of S100 family members in epidermal tumors and their clinical significance. OBJECTIVE: To determine the expression of S100A2, S100A4, S100A6, S100A7, as well as matrix metalloproteinases 9 (MMP9) in a spectrum of epidermal tumors with benign and malignant characteristics. METHODS: Immunohistological staining was performed for S100A2, S100A4, S100A6, S100A7, and MMP9 in 101 cases of various types of epidermal tumors, viz., squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC), keratoacanthoma (KA), and seborrheic keratosis (SK). Thirteen specimens of normal skin (NS) served as control. RESULTS: S100A2, S100A6, and S100A7 positive immunostaining was variably observed in different epidermal tumors. S100A4 staining was not observed in any epidermal tumors, but was clearly visible in dendritic cells. MMP9 immunostaining was positive only in 22/26 (84.62%) of SCC and 2/15 (13.33%) of BD cases. Expression of S100A2, S100A6, and S100A7 was increased in tumor cells compared to NS. However, only S100A6 expression was significantly associated with malignant transformation of epidermal tumors. Moreover, S100A6 expression was correlated with MMP9 expression in metastatic SCC. CONCLUSIONS: Epidermal tumors show increased expression of S100A2 and S100A7 proteins. S100A4 may be a useful and distinct marker for epidermal dendritic cells. Expression of S100A6 and MMP9 in combination is associated with the development of SCC.

Histamine-induced IL-6 and IL-8 production are differentially modulated by IFN-gamma and IL-4 in human keratinocytes.

It is known that large amounts of histamine are stored in mast cells located in the superficial dermis of the skin and can be released upon appropriate stimulation. However, the effects of histamine on keratinocyte function have not been well characterized. We therefore examined the capacity of histamine to modulate the production of interleukin (IL)-6 and IL-8 by keratinocytes. We found that histamine significantly augmented the production of IL-6 and IL-8 in a dose- and time-dependent manner. The enhancing effects of histamine were completely inhibited by a potent H1 receptor (H1R) antagonist, emedastine difumarate. Pyrilamine (a much weaker H1R antagonist) and cimetidine (an H2R antagonist) only partially inhibited the enhancing effects of histamine. The histamine-induced up-regulation of IL-6 and IL-8 production, however, was completely abrogated by a combination of pyrilamine and cimetidine. The IL-6 production was significantly enhanced by interferon (IFN)-gamma. Interestingly, IFN-gamma and IL-4 both significantly augmented the histamine-induced IL-6 production. On the other hand, the production of IL-8 was inhibited by IFN-gamma, and IFN-gamma and IL-4 both completely abrogated the histamine-induced IL-8 production. These results suggest that the histamine-induced IL-6 production and IL-8 production are differentially regulated by IFN-gamma and IL-4. Histamine may be an important modulator of cytokine production in epidermal milieu.