日本の伝統的な漢方薬である大建中湯は推進性の運動パターンを誘導することにより結腸輸送を促進する

Background: The traditional Japanese herbal medicine, daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon. Methods: The entire colon or segments of the proximal colon in rats were isolated and placed in Krebs solution. The motility of the colon was evaluated by analyzing spatiotemporal maps of diameter derived from video imaging and measuring the intraluminal pressure in the anal end of the proximal colon, and the transit time of a plastic bead through the entire isolated colon. Key Results: Several types of propagating contractions were observed in the isolated entire colon. When DKT was added to Krebs solution, the frequency of large‐extent anal propagating contractions increased. DKT treatment increased the intraluminal pressure in the isolated proximal colon, which was related to the propagating contractions. This effect was abolished by treatment with the neural blocker tetrodotoxin. These findings suggest DKT induced peristaltic contractions in the isolated colon. DKT accelerated colonic transit activity, which was related to peristaltic contractions induction in the colon. These effects were also observed in the colons treated with bethanechol and the active ingredient of DKT, hydroxy‐α‐sanshool. Conclusions and Inferences: Daikenchuto could enhance colonic transit activity by inducing peristaltic contractions, which may be mediated by the activation of the enteric nervous system in the colon

Comprehensive gene expression analysis of 5\u27-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma

金沢大学医薬保健研究域医学系To elucidate the molecular feature of human hepatocellular carcinoma (HCC), we performed 5\u27-end serial analysis of gene expression (5\u27SAGE), which allows genome-wide identification of transcription start sites in addition to quantification of mRNA transcripts. Three 5\u27SAGE libraries were generated from normal human liver (NL), non-B, non-C HCC tumor (T), and background non-tumor tissues (NT). We obtained 226,834 tags from these libraries and mapped them to the genomic sequences of a total of 8,410 genes using RefSeq database. We identified several novel transcripts specifically expressed in HCC including those mapped to the intronic regions. Among them, we confirmed the transcripts initiated from the introns of a gene encoding acyl-coenzyme A oxidase 2 (. ACOX2). The expression of these transcript variants were up-regulated in HCC and showed a different pattern compared with that of ordinary ACOX2 mRNA. The present results indicate that the transcription initiation of a subset of genes may be distinctively altered in HCC, which may suggest the utility of intronic RNAs as surrogate tumor markers. © 2010 Elsevier Inc

Prevalence of twitching motility in Pseudomonas aeruginosa isolated from medical facilities -Prevalence of TM in P. aeruginosa isolated from medical facilities-

Pseudomonas aeruginosa is an opportunistic bacterial pathogen, the infection system of which includes the possession of type IV pili. Type IV pili-dependent twitching motility (TM) is important for attachment to the epithelium and biofilm formation. Accordingly, there is a close relationship between the expression of pili and infection through intermediate biofilm formation. However, not all isolated strains of P. aeruginosa carry the pili-motility function. In this study, we isolated P. aeruginosa strains from various medical facilities and determined the TM prevalence. A total of 27 strains were isolated from bathrooms and nursing station sinks, 52% of which possessed clear TM ability. The strength of the TM ability differed by strain, with 15% indicating a marked ability. These results support the possibility that some of P. aeruginosa strains isolated from medical facilities can act as causative organisms of infection

Combined insulin B:9-23 self-peptide and polyinosinic-polycytidylic acid accelerate insulitis but inhibit development of diabetes by increasing the proportion of CD4+Foxp3+ regulatory T cells in the islets in non-obese diabetic mice.

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice

Rhodium(I)-Catalyzed Cycloisomerization of 1,6-Enynes

A new and unexpected Rh(I)-catalyzed cycloisomerization of 1,6-enynes is reported. Several different alkyne substitution patterns were evaluated under the reaction conditions, including a deuterated derivative that provides some insight into the reaction mechanism