Search

BACKGROUND Inclusion of female authors has been noted as potentially beneficial in the development of medical guidelines. Japanese professional committees representing allergic subspecialties develop practical guidelines with recommendations to caregivers, but these committees may be influenced by their gender composition. The objective of our study was to examine the influence of gender in developing pediatric allergic disease guidelines in Japan from 1999 to 2020. METHODS We examined the gender differences among the guideline committee members: allergic rhinitis, atopic dermatitis, bronchial asthma, and food allergies in Japan. We examined the gender composition of the committees, annual trends, and differences in guideline content. RESULTS The median proportion of women members among the 22 guidelines committees was 6.6% (range: 0%-27.3%). The analysis of the quadrant period did not show a significant increase in the proportion of female members. The food allergy group had a significantly higher proportion of female members than other guidelines (P < 0.01), but the proportion decreased from 25% to 14.3% during the observation period. For the pediatric asthma guidelines, the proportion of female committee members decreased from 5.3% in the 2000 version to 0% in the most recent revision in 2017. CONCLUSIONS The proportion of women on the committees that develop pediatric guidelines continues to be low and has not improved over the past 20 years.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although ω-3 fatty acids are known to have antiinflammatory effects, their effect against NEC remains unclear.Mother rats fed a soybean-based, docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diet from days 7 to 20 of gestation were examined. On day 20, the rat pups were delivered by abdominal incision, their intestines were removed, and messenger RNA was extracted. A rat NEC model was used to confirm the effects of ω-3 fatty acids on the inflamed intestine (n = 20-28). The expression of inflammatory molecules was analyzed by real-time polymerase chain reaction (n = 11-14).The concentrations of DHA and EPA in the intestine were significantly increased in the DHA and EPA groups (P.01). The expression of the antiinflammatory prostaglandin E2 receptor EP3 was increased in the DHA (P.05) and EPA groups (P.01). In the NEC model, the reduced incidence of colitis was confirmed in the DHA and EPA groups. The expression of peroxisome proliferator-activated receptor γ was increased (P.05), and the inhibitor of nuclear factor-κB α/β decreased in both the DHA (P.01) and EPA groups (P.05).Our findings indicate that ω-3 fatty acids are beneficial for protecting the premature intestine from inflammation by regulating eicosanoid- and nuclear factor-κB-related metabolite expression.

Although rectal bleeding in infancy (RBI) is not a rare phenomenon, the clinical course of RBI is not fully understood.To investigate the outcome and pathogenesis of RBI, especially when concomitant with food-protein-induced proctocolitis (FPIP) and neonatal transient eosinophilic colitis (NTEC), 22 neonates with rectal bleeding with FPIP and NTEC from January 2008 to June 2012 were enrolled and their clinical course and mechanisms of inflammation were examined.Thirteen infants showed rectal bleeding after feeding and were diagnosed with FPIP, and nine infants showed rectal bleeding before feeding and were diagnosed with NTEC. Elevated peripheral white blood cell (12,685 ± 3754/μl and 30,978 ± 16,166/μl) and eosinophil (1084 ± 816/μl and 4456 ± 3341/μl) were confirmed in FPIP and NTEC, respectively. Colonoscopy revealed nodular lymphoid hyperplasia, a pale mucosal surface and oozing with diffuse infiltration of neutrophils, lymphocytes, and eosinophils in both groups. Reverse transcription polymerase chain reaction analysis revealed enhanced expression of the interleukin-6, CCL11, and CXCL13 genes, where CXCL13 expression was more prominent in FPIP. Mucosal infiltration by CD3- and immunoglobulin-A- but not immunoglobulin-E-positive cells was confirmed. Among them, only one infant with FPIP developed milk allergy, whereas none with NTEC had developed milk allergy at the age of 1 year.FPIP in infancy and NTEC are similar diseases and interleukin-6, CCL11, and CXCL13 may play a major role in the pathogenesis of rectal bleeding. Although the involvement of allergic reaction is possible, milk allergy was not a common outcome after 1 year of follow up.

The IL1RL1/ST2 gene encodes a receptor for IL-33. Signaling from IL1RL1/ST2 induced by IL-33 binding was recently identified as a modulator of the Th2 response. The target cells for IL-33 are restricted in some hematopoietic lineages, including mast cells, basophils, eosinophils, Th2 cells, natural killer cells, and dendritic cells. To clarify the molecular mechanisms of cell type-specific IL1RL1/ST2 expression in mast cells and basophils, transcriptional regulation of the human IL1RL1/ST2 promoter was investigated using the mast cell line LAD2 and the basophilic cell line KU812. Reporter assays suggested that two GATA motifs just upstream of the transcription start site in the ST2 promoter are critical for transcriptional activity. These two GATA motifs possess the capacity to bind GATA1 and GATA2 in EMSA. ChIP assay showed that GATA2, but not GATA1, bound to the ST2 promoter in LAD2 cells and that histone H3 at the ST2 promoter was acetylated in LAD2 cells, whereas binding of GATA1 and GATA2 to the ST2 promoter was detected in KU812 cells. Knockdown of GATA2 mRNA by siRNA reduced ST2 mRNA levels in KU812 and LAD2 cells and ST2 protein levels in LAD2 cells; in contrast, GATA1 siRNA transfection up-regulated ST2 mRNA levels in KU812 cells. The ST2 promoter was transactivated by GATA2 and repressed by GATA1 in coexpression analysis. When these siRNAs were introduced into human peripheral blood basophils, GATA2 siRNA reduced ST2 mRNA, whereas GATA1 siRNA up-regulated ST2 mRNA. These results indicate that GATA2 and GATA1 positively and negatively control human ST2 gene transcription, respectively.

Ribavirin-related anemia is a serious side-effect of the pegylated interferon and ribavirin therapy used for hepatitis C, and may be cause for a reduction in ribavirin dose or even cessation of treatment. The aim of this study was to evaluate the prophylactic effects of oral eicosapentaenoic acid (EPA) supplementation on ribavirin-induced hemolytic anemia in pediatric and young adult patients.Twelve chronic hepatitis C patients ranging in age from 3 to 21 years (mean, 13.9 ± 5.1 years) who received pegylated interferon α-2b and ribavirin combination therapy were randomized to either the control group (n = 6) or EPA group (n = 6). Blood samples were collected before, and at 4, 8, and 16 weeks after treatment to measure clinical laboratory parameters.The reduction in hemoglobin levels of the EPA group was significantly ameliorated at 8 and 16 weeks when compared to the control group (P0.05). There was no significant difference in plasma ribavirin concentrations between the two groups during the treatment. However, one patient in the control group had a reduction in ribavirin dose.EPA supplementation prevented ribavirin-induced hemolytic anemia during combination therapy with pegylated interferon α-2b and ribavirin in pediatric and young adult patients.

6-Mercaptopurine (6-MP) and azathioprine (AZA) are widely used as maintenance therapy in children with inflammatory bowel disease (IBD). However, proper 6-thioguanine nucleotide (6-TGN) concentrations in Japanese children with IBD have not been reported.This retrospective review examines 32 ulcerative colitis (UC) patients and 19 Crohn's disease (CD) patients (12.87 ± 3.56 years) who required 6-MP or AZA to maintain disease remission. All patients were treated with 6-MP or AZA for at least 3 weeks prior to this study in addition to previous treatment. 6-MP dose, 6-TGN levels, assayed by high-performance liquid chromatography, as well as laboratory data were evaluated.Thirty-five children were successfully kept in remission with 6-MP and AZA therapy after weaning off corticosteroids. Overall, 123 measurements (59 active disease, 64 in remission) were analyzed. The mean 6-TGN concentration of the entire study population was 499.61 ± 249.35 pmol/8 × 10(8) red blood cell. The mean 6-MP dose in patients with active disease (0.910 ± 0.326 mg/kg per day) was significantly higher than for patients in remission (0.749 ± 0.225) (P = 0.0016). A significant inverse correlation was found between white blood cell counts and 6-TGN concentrations (r = 0.275, P0.002). Two patients experienced leukopenia with alopecia, and four transiently experienced increased serum levels of pancreatic enzymes, although no thiopurine S-methyl transferase mutations were confirmed.The doses of 6-MP or AZA needed to maintain remission in Japanese children with IBD are lower than those reported in Western countries. However, 6-TGN concentrations in this population are higher than previously reported.