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Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT.HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed.HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism.HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.

The townscape reflect the social background and values of people of each period. Although many buildings and towns were destroyed, people have to know those values. On the other hand, a huge number of photos had been shot since cameras became popular. This chapter deals with the values of those film photos as records of townscapes. In this research, two applications were developed to recognize the change of townscapes by using old photos and carried out demonstration experiments. Results of experiments are shown. In addition, the change of values of photos by implementation as contents of applications and the possibility of photo archives are considered.

Psoriasis is a chronic autoimmune inflammatory disease for which there is no cure, it results in skin lesions and has a strong negative impact on patients&rsquo, quality of life. Fucoidan from Cladosiphon okamuranus is a dietary seaweed fiber with immunostimulatory effects. The present study reports that the administration of fucoidan provided symptomatic relief of facial itching and altered the gut environment in the TNF receptor-associated factor 3-interacting protein 2 (Traf3ip2) mutant mice (m-Traf3ip2 mice), the Traf3ip2 mutation was responsible for psoriasis in the mouse model used in this study. A fucoidan diet ameliorated symptoms of psoriasis and decreased facial scratching. In fecal microbiota analysis, the fucoidan diet drastically altered the presence of major intestinal opportunistic microbiota. At the same time, the fucoidan diet increased mucin volume in ileum and feces, and IgA contents in cecum. These results suggest that dietary fucoidan may play a significant role in the prevention of dysfunctional immune diseases by improving the intestinal environment and increasing the production of substances that protect the immune system.

Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (α7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI. Keywords: Anti-inflammatory activity, Postoperative ileus, Zingiberis processum rhizoma, Neutrophil infiltration, Daikenchuto

Aim 13C-butyrate breath test is a non-invasive method for detecting inflammation in experimental colitis. We investigated whether this test could assess the anti-inflammatory effect of kampo medicines in dextran sulfate sodium salt (DSS)-murine colitis. Methods 13CO2 excretion was measured on 13C-butyrate breath test, after rectal instillation of butyrate in a DSS colitis model. Colon length, myeloperoxidase activity, and histological damage were also analyzed to evaluate inflammation. Results 13CO2 excretion in the DSS groups was significantly lower than in the normal group. Orengedokuto (OGT) and saireito (SRT) improve inflammation in DSS murine colitis, and this was reflected in the significantly higher 13CO2 excretion in the OGT- and SRT-treated DSS murine colitis groups compared with the vehicle (i.e. control) group. Conclusion 13C-butyrate breath test is a new non-invasive evaluation and screening method for the anti-inflammatory effect of kampo medicines.

Upper gastrointestinal (GI) motility is affected by various drugs and diseases. However, changes in upper GI motility during these conditions are not well understood, as there are few quantitative in vivo methods that assess small intestinal motility in mice. Ultrasonography is a noninvasive method for imaging and evaluating the condition of the abdominal organs. The aim of the present study was to establish a novel method for evaluating small intestinal motility by using ultrasonography in mice. We measured GI motility with and without loperamide, an antidiarrheal medication, by intestinal transit using an orally administered dye, a 13C-octanoic acid breath test, and ultrasonography. Locomotion activity of the duodenal wall was used for quantifying the GI motility observed via ultrasonography. Our results showed that upper GI transit was significantly delayed by loperamide. The 13C-octanoic acid breath test revealed decreased gastric emptying in loperamide-treated mice. Through ultrasonography, large peristaltic movements were observed in the duodenum of the control mice. In contrast, after treatment with loperamide, these peristaltic movements were suppressed, and the duodenal lumen was enlarged, suggesting decreased duodenal motility. In accordance with these results, quantifiable locomotion activity was also significantly decreased. In conclusion, ultrasonography is an effective in vivo method to quantify small intestinal motility in mice.

Postoperative ileus is a common complication after intra-abdominal surgery. Nitric oxide produced by macrophages in the inflamed gastrointestinal tract plays a crucial role in the pathogeny of postoperative ileus. Honokiol, extracted from the bark of Magnolia spp., is a natural compound with a biphenolic structure. In the present study, we examined the effect of honokiol on postoperative ileus and discussed its site of action. Postoperative ileus model mice were generated by surgical intestinal manipulation. Mice were administered honokiol (10 mg kg−1, per os) 1 h before and after intestinal manipulation. Gastrointestinal transit, leukocyte infiltration, and messenger RNA (mRNA) expression of inflammatory mediators were measured in postoperative ileus model mice with or without honokiol. We also investigated the inflammatory effect of honokiol in lipopolysaccharide-stimulated peritoneal macrophages. Gastrointestinal transit was delayed in postoperative ileus model mice and honokiol recovered the impaired transit. Honokiol significantly inhibited leukocyte infiltration and upregulation of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and inducible nitric oxide synthase in the ileal muscle layer of postoperative ileus model mice. In peritoneal macrophages activated by lipopolysaccharide, honokiol significantly inhibited the upregulated mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Honokiol significantly recovered gastrointestinal dysmotility and inhibited intestinal inflammation in postoperative ileus. Moreover, honokiol was suggested to have effects on macrophages, namely, inhibiting mRNA expression of proinflammatory cytokines and inducible nitric oxide synthase. Taken together, honokiol represents a potential novel therapeutic agent for postoperative ileus.

Rikkunshito (RKT), a Kampo (Japanese herbal) medicine, is used as a prokinetic for patients with various diseases including functional dyspepsia. RKT promotes delayed gastric emptying via 5-HT3 receptor blockade. Otherwise, RKT increases ghrelin release via 5-HT2B and 5-HT2C receptor activation. Recent studies revealed that ghrelin and 5-HT3 receptor antagonists have an anti-inflammatory effect. So we hypothesize that RKT may have an anti-inflammatory action in the post-operative ileus. Intestinal manipulation (IM) was applied to the distal ileum of mice. RKT was administered orally 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, and gastric emptying were analyzed. We also investigated the effects of the 5-HT3 receptor agonist m-chlorophenylbiguamide (mCPBG) and ghrelin-receptor antagonist [d-Lys3]-GHRP-6 on the ameliorative action of RKT. RKT treatment led to recovery of the delayed intestinal transit and gastric emptying rate induced by IM. RKT significantly inhibited the infiltration of neutrophils and macrophages. [d-Lys3]-GHRP-6 reduced and mCPBG partially reduced the RKT-mediated anti-inflammatory activity, as monitored by infiltrating macrophages and neutrophils. RKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency, in addition to prokinetic action. The RKT-induced anti-inflammatory activity may be partly mediated by inhibition of the 5-HT3 receptor and ghrelin release. Keywords:: anti-inflammatory action, rikkunshito, postoperative ileus, ghrelin, 5-HT3

The conventional method for the real-time assessment of murine colitis requires a large number of animals. The 13C-butyrate breath test could be useful for evaluating disease activity and the amelioration of human ulcerative colitis non-invasively. The purpose of this study was to investigate whether this test can be used to assess the phase of inflammation in murine colitis. We investigated the excretion of 13CO2 measured by the 13C-butyrate breath test after rectal instillation of butyrate in the DSS colitis model. The colon length, MPO activity, and histological damage were analyzed as parameters. The efficacy of salicylazosulfa-pyridine (SASP) on 13CO2 excretion was also studied. The 13CO2 excretion curves in the 0.5% DSS– and 0.75% DSS–treated groups were significantly lower than those in the normal group (P < 0.01, P < 0.01). Good correlation between the results of the breath test and the inflammation parameters was observed. The 13CO2 excretion curve in DSS murine colitis after the administration of SASP was significantly higher than in the normal group (P < 0.01). The 13C-butyrate breath test can be used to evaluate the inflammatory phase of DSS murine colitis, and it may be a new non-invasive method for assessing murine colitis. Keywords:: 13C-butyrate breath test, intestinal inflammation, murine colitis

In clinical and experimental settings, the (13)C breath test is performed to measure gastric emptying and has advantages of noninvasiveness and repeatability. We intended to apply the (13)C breath test method to mice with an easy-to-handle solid test meal that is more physiological than liquid meals. Male ddY mice were trained to eat (13)C-acetate-containing pellets as the solid test meal. Thirty minutes after administration of metoclopramide (0.3-3 mg/kg, p.o.) or atropine sulfate (0.3-3 mg/kg, i.p.), mice received the test meal and were placed in chambers. The (13)CO(2) levels in the expired air were measured and the maximum concentration (C(max); per thousand) and the time to reach the maximum concentration (T(max); min) were determined. Metoclopramide significantly and dose-dependently increased C(max) and decreased T(max). On the other hand, atropine sulfate significantly and dose-dependently decreased C(max) and increased T(max). The (13)C-acetate breath test using a solid test meal is sensitive enough to detect both enhanced and delayed gastric emptying of the reference drugs.

The purpose of this study was to reevaluate the sho of goshuyuto, which has been established in an unscientific manner, and to create a new concept of the sho of goshuyuto. Eighty-four patients suffering from chronic headache were instructed to orally consume 7.5g. day of a spray-dried powder of goshuyuto (TJ-31) for 4 weeks. Before consuming the TJ-31, all subjects underwent Kampo examinations that were based on 43 diagnostic items. After the 4-week period of medication, all the subjects were classified as either responders or nonresponders. After excluding insignificant items from the 43 diagnostic items, discriminant analysis, which discriminated between responders and nonresponders, was conducted. Of the 80 subjects who completed the trial period, 57 were judged to be responders and 23 to be nonresponders. “Cold feet,” “fluid and gas retention in the stomach,” “kyokyo-kuman,” “tenderness at side of navel,” and “pulsation at abdomen” were selected by stepwise selection. The results of the discriminant analysis using these 5 items suggest that 28 subjects were misclassified and that the misclassification rate was 35%. Of the actual 23 nonresponders, 20 were accurately discriminated as nonresponders. The 5 selected items are suggested to be more useful in selecting the nonresponders than the responders. In conclusion, the empirically established sho of goshuyuto seemed to not be abele to completely explain the indication of goshuyuto. However, the inclusion of “tenderness at side of navel” and “pulsation at abdomen,” as new components comprising the sho of goshuyuto, may facilitate a more accurate indication of goshuyuto.

We propose a simple parameter that improves prediction of the number of CD34(+) cells in blood cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation following administration of granulocyte colony-stimulating factor. The percentage of immature granulocytes including myeloblasts, promyelocytes, myelocytes, and metamyelocytes (LSI for left-shift index) immediately prior to the start of each apheresis correlated with the number of CD34(+) cells in PBSC collections (r = 0.79, P0.0001, Y = 0.227X - 0.99, R(2) = 0.623) much better than did the white blood cell count (r = 0.07), currently the most commonly used predictor in deciding the initiation of apheresis. We then used receiver operating characteristic (ROC) curves to determine a cutoff point for LSI to prevent unnecessary apheresis. At LSI7.5, sensitivity and specificity of cutoff points in the probability of obtaining1.0 x 10(6) CD34(+) cells/kg BW were 93.3% and 94.3% (95% CI, 91.4-100.0%), respectively. When LSI reaches 15.25, nearly 100% of apheresis will attain the target CD34(+) cell dose. These findings indicate that LSI is a useful and simple method for predicting the yield of CD34(+) cells before the start of PBSC collection and avoiding unnecessary apheresis.

Background We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action. Methods The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. Key Results Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT4R) knockout mice. Conclusions & Inferences Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT4R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI.

Bisphenol A, an environmental oestrogenic chemical, was found to conjugate highly with glucuronic acid in male rat liver microsomes studied in vitro. In the various isoforms tested (1A1, 1A3, 1A5, 1A6, 1A7 and 2B1), glucuronidation of bisphenol A and of diethylstilboestrol, a synthetic crystalline compound possessing oestrogenic activity and known to be glucuronidated by liver microsomes, was catalysed by an isoform of UDP-glucuronosyltransferase (UGT), namely UGT2B1, which glucuronidates some endogenous androgens. UGT activity towards bisphenol A in liver microsomes and in UGT2B1 expressed in yeast AH22 cells (22.9 and 0.58 nmol/min per mg of microsomal proteins respectively) was higher than that towards diethylstilboestrol (75.0 and 4.66 pmol/min per mg of microsomal proteins respectively). UGT activities towards both bisphenol A and diethylstilboestrol were distributed mainly in the liver but were also observed at substantial levels in the kidney and testis. Northern blot analysis disclosed the presence of UGT2B1 solely in the liver, and about 65% of the male rat liver microsomal UGT activities towards bisphenol A were absorbed by the anti-UGT2B1 antibody. These results indicate that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isoform of UGT.

Single crystal X-ray diffraction and 13 C NMR spectroscopic study of two new N -arylpiperidines 4 and 6 reveals that 4 adopts the conformation with the axial N-aryl bond in crystals in contrast to the general tendency of N -arylpiperidines to assume the conformation with an equatorial N-aryl bond. It is shown that the degree of pyramidalization of the nitrogen atom and the orientation of the N-aryl bond are strongly affected by intermolecular interactions in crystals.

Glucagon-like peptide-1 (GLP-1) is released from the gut in response to nutrient ingestion. Intravenous (iv) administration of GLP-1 (50 pmol-20 nmol) elicited dose-dependent increases in the rate of whole-body O2 consumption (VO2), an index of energy expenditure, and heart rate of urethane-anesthetized rats. The body core (colonic) temperature increased up to 0.3 degrees C without accompanying alteration of tail skin temperature. Intracerebroventricular (icv) administration of GLP-1 induced a slower and smaller increase in VO2 than the intravenous administration. The injection of glucagon-like peptide-2 (iv or icv) had no effect on VO2, body temperatures, or heart rate. Decerebration had no effect on the thermogenic responses induced by the iv administration of GLP-1, suggesting that the forebrain is not essential for these responses. However, cervical spinal transection greatly attenuated the responses, suggesting the critical involvement of the lower brainstem. Adrenalectomy or pretreatment with an autonomic ganglion blocker, hexamethonium, or a beta-adrenergic blocker, propranolol, also significantly attenuated the thermogenic response. However, subdiaphragmatic vagotomy or celiac-superior mesenteric ganglionectomy had no effect. Rats made insulin-deficient by pretreatment with streptozotocin also exhibited the normal thermogenic response to GLP-1. These results suggest the involvement of the GLP-1 in postprandial energy expenditure, mediated by the lower brainstem and sympathoadrenal system.

Background. Toe flexor muscle strength determines the anterior limit of the functional base of support, thereby affecting a standing individual's maximum forward reach or lean capacity. We developed a method for measuringtoe flexor muscle strength in order to test the null hypotheses that it is neither affected by age nor gender. Methods. Gender-balanced groups of 20 healthy young adults (YA) (average age 22.8 years) and 20 healthy older adults (OA) (average age 73.2 years) participated in the study. Toe flexor isometric muscle strength, calculated as the maximum volitional moment developed simultaneously in the sagittal plane by the toe flexor muscles about a reference axis through the first metatarsophalangeal joint, was measured in three trials while subjects reached forward as far as possible while standing on a force plate. Results. Significant age (p

Background Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action. Method Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice. Results DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice. Conclusions In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.