Consensus statements on pediatric atopic dermatitis from dermatology and pediatrics practitioners in Japan: Goals of treatment and topical therapy.

BACKGROUND: Pediatric atopic dermatitis (PAD) is a pluricausal disease and is frequently seen in dermatological and pediatric practice. Therefore, it is important to find common views in clinical practice and to promote consensus among practitioners. Aiming to obtain common views among dermatologists and pediatricians and to disseminate them widely in clinical practice, we held the PAD Consensus Forums described herein. METHODS: Questionnaire surveys of treatment goals and drug therapy were conducted to prepare topics for discussion at the PAD Consensus Forums. Reaching consensus was defined as agreement among at least 70% of the participants. RESULTS: As a result of discussion among 24 dermatologists and 25 pediatricians, consensus was obtained on 7 topics. These topics configure 3 consensus of treatment goals (Attainment targets were divided into the short/medium term and the long term. Attainment targets were associated with the primary evaluation domains of the Harmonising Outcome Measures for Eczema (HOME) roadmap, etc.) and 4 consensus of drug therapy (The number of applications of topical anti-inflammatory drugs in the acute phase and selection and ideal intervals between applications of topical anti-inflammatory drugs in proactive therapy, etc.). CONCLUSIONS: The consensus is expected to help practitioners set appropriate treatment goals in clinical practice and facilitate the choice of drugs for treatment.

Drug Utilization and Medical Cost Study Focusing on Moisturizers in Cancer Patients Treated with Molecular Targeted Therapy: A Retrospective Observational Study Using Data from a Japanese Claims Database.

INTRODUCTION: Molecular targeted therapies (MTTs) cause skin disorders in patients with cancer, and moisturizers are useful treatments; however, their actual use and costs are unknown. Our purpose was to examine the use and costs of moisturizers prescribed for xerosis (asteatosis) in patients with cancer treated with MTTs. METHODS: We used data from a Japanese hospital-based claims database. The index date was the first date of MTT prescription from October 2011 to April 2018 (selection period), and the follow-up period was 1 year from the index date. Patients treated with MTTs during the selection period and who were not prescribed moisturizers in the 6 months before the index date were included as the study cohort. Timing, duration, amount, and costs of the prescribed moisturizers and total medical costs were analyzed. RESULTS: Among the 78,190 patients in the study cohort, 27,906 patients (35.7%) were prescribed moisturizers during follow-up. Moisturizer prescription timing, duration, and volume were inconsistent. The average annual total medical costs for treating patients with MTT who were prescribed moisturizers was JPY 6.165 million (USD 53,797) per patient, and the moisturizer costs were JPY 6033 (USD 53). The number of patients who used moisturizers showed an increasing trend. CONCLUSION: No consistent patterns were observed for the timing or duration of moisturizer use, which suggests various developmental patterns of skin disorders. Furthermore, medical costs for moisturizers accounted for only a small proportion of the total medical costs required for cancer treatment.

Efficacy of a moisturizer for pruritus accompanied by xerosis in patients undergoing dialysis: A multicenter, open-label, randomized verification study.

Xerosis and pruritus are common in patients undergoing dialysis. These symptoms are treated with moisturizers, but limited evidence supports the efficacy of such treatment. Our exploratory study suggested the effectiveness of a heparinoid-containing product for xerosis in dialysis patients. We conducted a multicenter, open-label, randomized, before-after, parallel-group comparative study to verify the exploratory study results (Clinical Trial Registry: UMIN000029360). Seventy-one Japanese patients undergoing dialysis with chronic kidney disease and xerosis were randomly assigned to receive a heparinoid-containing product for 2 weeks (group A [n = 36]) or 8 weeks (group B [n = 35]). Patients were instructed to apply the study product based on the fingertip unit method. The efficacy endpoints were the water content of the stratum corneum (WCSC), skin dryness score, pruritus visual analog scale score, and Dermatology Life Quality Index. Safety was assessed by monitoring adverse events. The mean WCSC (arbitrary units) was 26.0 ± 9.6 in group A and 25.2 ± 10.0 in group B at the start of treatment (week 0), significantly increased to 39.0±12.5 in group A and 38.5 ± 11.0 in group B (P < 0.0001 for both vs week 0) by week 2, and then decreased only in group A. Thus, the WCSC at week 4 (the primary endpoint) remained significantly higher in group B (36.4 ± 12.2 vs 28.8 ± 10.4; P = 0.0068). Other endpoints improved during treatment with the study product. One patient developed a rash and erythema as treatment-related adverse events. In conclusion, 8 weeks' application of a heparinoid-containing product was effective for xerosis in patients undergoing dialysis.

Differentiation of sulfate and phosphate by H/D exchange mass spectrometry: application to isoflavone.

Often phosphorylation or sulfation is an important step which occurs in the signal transduction and cascade of metabolic pathways. Some natural products and metabolites contain one or more sulfate or phosphate groups. Isoflavone sulfate has been identified from high-resolution mass spectrometry (HRMS) and enzymatic digestion by sulfatase. We previously reported the new water-soluble isoflavone analogs, daidzein 7-O-phosphate and genistein 7-O-phosphate, which were surprisingly hydrolyzed by sulfatase. In this previous study, we could not determine the phosphate from the results of HRMS and enzymatic digestion, that is, HRMS and enzymatic digestion did not provide clear evidence. In this case, we drew conclusions from NMR analysis. HRMS has been ineffective with a regular fast atom bombardment (FAB) mass spectrometer to distinguish between phosphate and sulfate since the mass difference is only 0.009 mass units. There was, however, no conventional method of microanalysis to distinguish phosphate from sulfate owing to the same nominal mass. It is still very difficult to determine by negative FABMS [--O--P(==O)(OH)(2)] = 80 and [--O--S(==O)(2)OH] = 80. In this paper, we report a method to distinguish between these groups by using a popular low-resolution mass instrument; thus, phosphate and sulfate were measured by H/D exchange mass spectrometry at the picomole level to differentiate [--O--P(==O)(OD)(2)] = 82 and [--O--S(==O)(2)OD] = 81, respectively. This method is applicable not only to the isoflavone, but also to other phospho and sulfo compounds.

The synthesis and nicotinic binding activity of (+/-)-epiquinamide and (+/-)-C(1)-epiepiquinamide.

The synthesis of (+/-)-epiquinamide 1 and (+/-)-C(1)-epiepiquinamide 2 based on the use of a Curtius rearrangement to introduce the C(1) amino residue is reported. In a competition binding assay for [(3)H]epibatidine binding to rat brain membranes neither (+/-)-1 nor (+/-)-2 showed any significant level of nicotinic activity.

Synthesis of beta-analogues of C-mannosyltryptophan, a novel C-glycosylamino acid found in proteins.

alpha-C-Mannosyltryptophan (alpha-C-Man-Trp) has been found to be a novel post-translational modification of tryptophan found from some biologically important glycoproteins. In order to analyze the biological functions of alpha-C-Man-Trp, we have developed an efficient synthetic strategy for alpha-C-Man-Trp and its glucose and galactose analogues, starting from alpha-C-glycosidation of the corresponding hexapyranoside derivatives with tinacetylene. According to the synthetic routes, we describe here syntheses of beta-anomers of C-Man-Trp, and its glucose and galactose analogues from the corresponding beta-C-glycosylacetylenes. During this study, we have developed a highly stereocontrolled synthesis of beta-C-mannosylacetylene that is required for the synthesis of beta-C-Man-Trp, while the precedented method gave an anomeric mixture of the C-mannosylacetylene. The synthetic C-Man-Trp and its analogues were analyzed by HPLC.

Isolation of brominated quinones showing chemiluminescence activity from luminous acorn worm, Ptychodera flava.

Luminous acorn worm, Ptychodera flava emits green light by stimulating with diluted hydrogen peroxide. We have recently reported isolation and structure determination of 2,3,5,6-tetrabromohydroquinone as a luminous substance and riboflavin as a possible light emitter. There are three other luminous substances in the extracts from P. flava, so here we report the isolation and structure determination of other luminous substances as 2,3,5-tribromohydroquinone, tetrabromo-1,4-benzoquinone, and 2,3,5-tribromo-6-(2,3,5-tribromo-4-hydroxy-phenoxy)-benzene-1,4-diol. Besides, this is the first report of isolation of tetrabromo-1,4-benzoquinone from acorn worm. Structure-activity relationship of chemiluminescence activity of halogenated quinone derivatives reveals that a highly halogen substitution and 1,4-quinone skeleton are important for high chemiluminescence activity.

Tetrabromohydroquinone and riboflavin are possibly responsible for green luminescence in the luminous acorn worm, Ptychodera flava.

2,3,5,6-Tetrabromohydroquinone was isolated as a luminous substance from Ptychodera flava. This compound emitted light after addition of hydrogen peroxide under basic conditions. Since hydroquinone had no fluorescence, further investigation by spectral analysis revealed that riboflavin was the only possible light emitter having green fluorescence. In the presence of both tetrabromohydroquinone and riboflavin under a basic condition containing 70% 1,4-dioxane, green light emission was observed following the addition of hydrogen peroxide. We succeeded in recording the same emission spectrum as that in the bioluminescence caused by the addition of aqueous diluted hydrogen peroxide solution in P. flava.