Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media.

OBJECTIVE: Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. METHODS: Children prone to recurrent AOM aged 6-48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10-0.25g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. RESULTS: At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61±0.54 vs. 1.07±0.72 AOM instances/month; P=0.005) and also significantly decreased number of coryza episodes (P=0.015) and total antibiotic administration (P=0.024). CONCLUSIONS: This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections.

Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma.

PURPOSE: Epigenetic changes such as DNA methylation play a key role in the development and progression of multiple myeloma. Our aim in the present study was to use genomic screening to identify genes targeted for epigenetic inactivation in multiple myeloma and assess their role in the development of resistance to dexamethasone. EXPERIMENTAL DESIGN: Gene expression was examined using microarray screening, reverse transcription-PCR, and real-time quantitative PCR. DNA methylation was examined using bisulfite PCR, bisulfite sequencing, and bisulfite pyrosequencing in 14 multiple myeloma cell lines, 87 multiple myeloma specimens, and 12 control bone marrow samples. WST-8 assays were used to assess cell viability after treatment with 5-aza-2'-deoxycytidine and/or dexamethasone. RESULTS: Microarray analysis was done to screen for genes up-regulated by 5-aza-2'-deoxycytidine. In RPMI8226 cells, 128 genes were up-regulated, whereas 83 genes were up-regulated in KMS12PE cells. Methylation of 22 genes with CpG islands in their 5' regions, including RASD1, was confirmed. Methylation of RASD1 was associated with its inactivation, which correlated with resistance to dexamethasone. Treating multiple myeloma cells with 5-aza-2'-deoxycytidine restored sensitivity to dexamethasone. Methylation of RASD1 was also detected in a subset of primary multiple myeloma specimens, and the levels of methylation were increased after repeated antitumor treatments. Gene signature analysis revealed various genes to be synergistically induced by treatment with a combination of 5-aza-2'-deoxycytidine plus dexamethasone. CONCLUSION: Our findings indicate that epigenetic inactivation of genes, including RASD1, plays a key role in the development of dexamethasone resistance in multiple myeloma. Moreover, they show the utility of demethylation therapy in cases of advanced multiple myeloma.

Effects of Japanese herbal medicine, Juzen-taiho-to, in otitis-prone children--a preliminary study.

CONCLUSION: Juzen-taiho-to (JTT, TJ-48), a Japanese herbal medicine that improves immune function, was found to be effective in otitis-prone in children. OBJECTIVE: To evaluate the efficacy of JTT against intractable and recurrent infections in immature immune systems, we administered JTT to otitis-prone infants and investigated clinical changes before and during JTT administration. SUBJECTS AND METHODS: Twenty-four otitis-prone infants were administered JTT at 0.10-0.14 g/kg/day twice a day for 3 months. We compared clinical course, such as frequency of acute otitis media (AOM), duration of fever and antibiotics administration, and hospital visits for the periods before and during JTT administration. RESULTS: Medication compliance rate was 87.5%, and administration of JTT led to remission in 95.2% patients. No apparent side effects were observed. The frequency of AOM decreased significantly (Wilcoxon signed rank test, p=0.000) with JTT. The duration of fever (p=0.000) and administration of antibiotics (p=0.001), as well as the number of hospital visits (p=0.001) and emergent hospital visits (p=0.000) showed significant decreases after JTT administration. After the end of the JTT period, 14 of 21 (66.7%) patients started to take it again, as they experienced purulent otitis media and/or other infections after discontinuation. The frequency of AOM increased significantly after stopping JTT (p=0.004) and decreased again with JTT resumption (p=0.005).

Identification and reverse genetic analysis of mitochondrial processing peptidase and the core protein of the cytochrome bc1 complex of Caenorhabditis elegans, a model parasitic nematode.

Mitochondria could be a good target for anti-parasitic drugs. The alpha and beta subunits of mitochondrial processing peptidase (MPP) and the core subunits of the cytochrome bc1 complex, UCR-1 and UCR-2, are homologous to one another and are important for mitochondrial functions. However, our knowledge of these proteins in nematodes is very limited. Caenorhabditis elegans, a free-living nematode, has six genes coding for proteins homologous to these subunits. On primary structure comparison, and immunochemical and enzymological analyses, the gene products were assigned as follows: Y71G12B.24, alpha-MPP; ZC410.2, beta-MPP; F56D2.1, UCR-1; VW06B3R.1, T10B10.2; and T24C4.1, UCR-2. The primary structures of beta-MPP and UCR-1 from Brugia malayi, a parasitic nematode causing human filariasis, were deduced from their cDNA structures. Phylogenetic analysis showed that the UCR-1s from both C. elegans and B. malayi were less related to mammalian UCR-1s than to MPPs from various organisms. MPP and the bc1 complex are essential for the life cycle of C. elegans, because their reverse genetic inhibition is lethal. This suggests the possibility that these proteins are also essential for the viability of B. malayi and other parasitic nematodes, and are potential targets for anti-parasitic agents.