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Modeling cluster dynamics or rate theory to describe the microstructural evolution of irradiated materials requires a precise knowledge of the migration energy of a self-interstitial atom (SIA), a ...

The different effects of intermittent and continuous stretching on the mechanical properties of the musculotendinous complex have been unclear. This study aimed to compare the effects of intermittent and continuous stretching for the same duration on the range of motion (ROM), passive resistive torque (PRT), and musculotendinous stiffness (MTS) of ankle plantar flexors. Eighteen healthy young men participated in the study. Intermittent (four sets × 30 s) and continuous stretching (one set × 120 s) were performed in random orders on two separate days. Both stretching protocols were conducted using a dynamometer with a constant torque applied. ROM and PRT were determined using a dynamometer, and MTS was calculated using the torque–angle relationship measured before and after stretching. Two-way repeated measures analysis of variance was performed for all parameters. Both intermittent and continuous stretching significantly increased ROM and decreased PRT and MTS (p &lt, 0.05). Intermittent stretching led to greater changes in ROM and PRT than continuous stretching. However, the reduction in MTS did not differ between the two conditions. These results suggest that intermittent stretching is more effective in increasing ROM and changing the mechanical properties of the musculotendinous complex.

An in- situ observation using high-voltage electron microscopy (HVEM) showed that the number density of stationary self-interstitial atom (SIA) clusters in electron-irradiated α-iron at room temper...

Obstructive colitis (OC) is a nonspecific inflammatory condition that occurs at the proximal side of a completely or partially stenotic lesion typically caused by colorectal cancer. Impaired blood flow caused by these stenotic changes in the colon or rectum results in this condition. During surgery for sigmoid colon carcinoma with OC, complete surgical removal of the OC lesions is required. However, it is difficult to anticipate the range of OC before surgery. Diagnosing the potential ischemia during surgery would decrease the need for re-operation. This is the first report of HyperEye Medical System (HEMS) angiography for surgery of colon cancer with OC. We report a case of sigmoid colon carcinoma in which HEMS angiography was used and found to be useful for real-time detection of the OC lesion.

The interaction between oxide particles and dislocations in a 9Cr-ODS ferritic steel is investigated by both static and in situ TEM observation under dynamic straining conditions and room temperatu...

We proposed a fabrication method for silicon nanospheres with diameters of 100-200 nm at arbitrary locations by using electron-beam lithography and hydrogen annealing. The nanospheres showed a strong magnetic field response in the visible region that was observed as scattered light emitted from the nanospheres. The scattering spectra were calculated by finite-difference time-domain simulation. Periodically arranged silicon nanospheres were successfully fabricated as designed, and the scattered light was measured by dark-field illumination microscopy. The scattering spectra were in the visible range, and the peak position was redshifted as the diameter increased.

Various types of nanometric defects such as voids and helium (He) bubbles produced by high-energy neutron irradiations are known to degrade the mechanical properties of irradiated materials. In this study, we have evaluated the obstacle strength of He bubbles to the mobility of an edge dislocation in α-iron for 2 and 4 nm bubbles with He-to-vacancy (He/V) ratios ranging from 0 to 1 at 300 and 500 K, by molecular dynamics simulation. Results showed that as the He/V ratio increases, the obstacle strength needed for the release of a dislocation from the bubble becomes stronger up to a moderate He/V ratio (0.6 and 0.4 for 2 and 4 nm bubbles, respectively, at both temperatures), and a further increase in the He/V ratio leads to weakening of the obstacle strength. For He/V = 1, the obstacle strengths are 10–30% weaker than those at moderate He/V ratios depending on the bubble size and temperature. The extent of obstacle strength was found to be correlated with the dilation caused by He bubbles depending...

Mesenteric panniculitis (MP) is a benign fibroinflammatory process characterized by the presence of fat necrosis, chronic inflammation and fibrosis in the mesentery. Although various causal factors, such as malignancy, chronic inflammatory conditions and autoimmune processes, have been identified, the precise etiology remains unknown. We herein report a rare case of MP accompanying Sjögren's syndrome in which a mass lesion and intestinal stenosis were observed simultaneously. This condition led to ileus, which was effectively treated using prednisolone.

Patients with type 2 diabetes mellitus are known to have an increased risk of colorectal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used as a new therapeutic tool for type 2 diabetes. Since the substrates for DPP-4 include intestinotrophic hormones and chemokines such as GLP-2 and stromal cell-derived factor-1 (SDF-1), which are associated with tumor progression, DPP-4 inhibitors may increase the risk of colorectal tumors. However, the influence of DPP-4 inhibitors on colorectal neoplasia in patients with type 2 diabetes remains unknown. In the present study, we show that long-term administration of a DPP-4 inhibitor, sitagliptin (STG), suppressed colon carcinogenesis in leptin-deficient (ob/ob) C57BL/6J mice. Colonic mucosal concentrations of glucagon‑like peptide-1 (GLP-1) and GLP-2 were significantly elevated in the ob/ob mice. However, mucosal GLP concentrations and the plasma level of SDF-1 were not affected by the administration of STG. Real‑time PCR analysis revealed that colonic mucosal IL-6 mRNA expression, which was significantly upregulated in the ob/ob mice, was significantly suppressed by the long-term administration of STG. These results suggest that a DPP-4 inhibitor may suppress colon carcinogenesis in mice with type 2 diabetes in a GLP-independent manner. Since DPP-4 has multiple biological functions, further studies analyzing other factors related to colon carcinogenesis are needed.

Background and Aim Luminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition.

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers.

Bubble dispersion strengthened copper (BDS-Cu) was synthesized by using the pyrolysis gaseous products of Poly (methyl methacrylate) (PMMA) during spark plasma sintering (SPS) process. Bubbles with an average diameter of 14 nm are densely dispersed in copper matrix with a dispersion distance 119 nm. Vickers׳ hardness of BDS-Cu is 400 MPa higher than that of pure copper. The strengthening effect is due to the dislocation pinning effect of bubbles.

We investigated the variation in body colour and its thermoregulatory function in Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae), a parasitoid wasp of Spodoptera and other free-living lepidopteran larvae. We show that the body colour of adult wasps darkens when cocoons are kept at low temperatures. The range in the variation in colour, however, differs for different parts of the body and among uniparental (thelytokous) strains. This melanism enables these wasps to attain a body temperature in sunshine up to 2°C. Moreover, this small gain in body temperature can markedly increase the flight activity of wasps at low ambient temperatures. We conclude that the variation in body colour that resulted from rearing the cocoons at different temperatures enable the wasps to adapt to changing thermal environments. The ecological significance of the difference in the degree of melanism of the different strains is discussed.

Adding Cr to heat-tolerant Co0.054Ni0.018Mg0.93O solid-solution catalysts for CH4/CO2/H2O reforming at 2.1 MPa allowed us to control the key properties determining the behavior of the supported catalysts, such as the reduction degree of the metal, metal particle size, and amount of exposed zerovalent metals. A small load of Cr [Cr/(Co + Ni) = 0.11 mol %] efficiently catalyzed Co2+ and Ni2+ reduction. This catalyst, which had abundant small alloy particles on the support material, resisted coking and oxidative deactivation, even under accelerated deterioration conditions. X-ray photoelectron spectroscopy, X-ray absorption near-edge structure, extended X-ray absorption fine structure, and scanning transmission electron microscopy–energy-dispersive X-ray measurements indicated that Cr existed as a trivalent cation in a CrxCo0.054Ni0.018Mg0.93O1+1.5x solid solution, leading to the formation of a divalent cation vacancy and that Cr3+ was abundant on the surface of the catalyst particles after calcination at 13...

The diffusion process of a single self-interstitial atom (SIA) in α-iron was studied by a hyper-molecular dynamics (hyper-MD) method that has been demonstrated to efficiently accelerate slow diffusive conformational transitions that occur in various materials. By adding a local bias potential, the acceleration of the dynamics becomes significantly higher at lower temperatures, e.g., on the order of 5 at 300 K, without changing the dynamics of the diffusion process as calculated using a conventional MD simulation. The validity of the results demonstrates that the hyper-MD method with an appropriate local bias potential can be applicable for determination of the diffusion process of SIAs in bulk materials.

Novel graft copolymers, PTPA- g -PEAs containing poly(triphenylamine) (PTPA) backbone and poly(ethyl acrylate) (PEA) branches were synthesized by the oxidative coupling polymerization of triarylamine monomers followed by grafting of ethyl acrylate via an atom transfer radical polymerization (ATRP). Photorefractive (PR) composites based on the graft copolymers showed good static PR properties and fast response time under moderate conditions. The highest diffraction efficiency (19.7% at 45 V/μm) was observed with the composite containing the graft polymer with 18 mol% of graft density and 27 wt% of PTPA. And the fastest response (8 ms at 50 V/μm) was achieved when PTPA content was 68 wt%.

Objective The calcineurin inhibitor tacrolimus has been shown to be safe and effective as salvage therapy for steroid-refractory ulcerative colitis (UC). Since differences in the onset of action between various agents are thought to influence the achievement and maintenance of disease remission, top-down or accelerated step-up therapy with tacrolimus may be useful. However, the efficacy of tacrolimus in moderate to severe UC patients not receiving concomitant steroids remains unknown. Methods Ten patients (11 attacks) with active, moderate to severe UC were treated with oral tacrolimus at a dose of 0.1 mg/kg body weight daily. The dosages were adapted to maintain trough whole-blood levels of 10 to 15 ng/mL to induce remission and 5 to 10 ng/mL to maintain remission. Lichtiger scores, the incidence of adverse effects (serum creatinine and glucose) and long-term outcomes were assessed. Results At four weeks after the initiation of tacrolimus therapy, clinical remissions were observed for eight attacks (72.7%) and clinical responses were demonstrated for three attacks. At 12 weeks after the initiation of tacrolimus treatment, clinical remissions were achieved for nine attacks (90%). After a mean follow-up of 10.4 months, clinical remissions were maintained for eight of 11 attacks. During the tacrolimus treatment, the serum creatinine and glucose levels were not significantly elevated. Conclusion Oral tacrolimus is a safe and effective therapy for the treatment of moderate to severe UC in patients not receiving concomitant treatment with systemic steroids. Although further studies are required to establish the efficacy and safety of oral tacrolimus therapy in patients with UC, oral tacrolimus may represent a top-down or accelerated step-up treatment option for patients with moderate to severe UC.

It is known that the presence of even a small amount of impurity in interstitial positions can, depending on temperature, have a drastic influence on the one-dimensional (1-D) motion of sel...

症例は25歳 女性．ダウン症候群と診断され，幼少期に心室中隔欠損症術を受けた際に輸血あり．20歳時にC型肝炎ウイルス（HCV）の感染を指摘された．肝機能異常あり，HCV genotype 2a，ウイルス量3.2 logIU/ml であった．インターフェロン適応ありと判断し，ペグインターフェロンα-2aを投与した．しかし白血球減少症を来し，以後インターフェロンβに切り替え投与した．その後合併症なく治療を完遂し，HCV-RNA陰性化およびトランスアミナーゼ正常化が得られた．ダウン症候群合併C型肝炎では，インターフェロンによるウイルス学的著効が得られる症例は稀とされている．また精神的な副作用を予測し難いため，治療をためらう事例も多い．しかし近年，ダウン症候群の余命は延長し，C型肝炎合併例では肝炎が予後を左右する場合もある．本症例は，ウイルス側および宿主側に著効し易い素因を持ち，かつインターフェロンβによる治療完遂が可能であった．この様な症例では積極的な抗ウイルス療法を考慮する必要がある．

Yersinia enterocolitica (YE) infection is a rare cause of intestinal intussusception, especially in adults. We herein, report a case of adult intussusception due to YE enterocolitis. A 24-year-old woman was admitted because of severe abdominal pain. She was clinically diagnosed with ileocolic intussusception on the basis of the findings of computed tomography (CT) and a gastrografin enema. Manual surgical reduction was sufficient to alleviate the intussusception. A histological examination of the lymph nodes around the ileocecum excluded lymphoma. Serological testing revealed that the cause of the intussusception was a YE infection. The patient's postoperative course was good and no recurrence was seen during the follow-up.

To examine the mechanism of huge swelling of V–Fe alloys, TEM observation was applied to V– x at.%Fe ( x = 0, 0.3, 1, 5, 7), after low-dose neutron irradiation of 0.1–1.17 dpa at 400–600 °C. Concentric Multi-Dislocation Loops (CMDLs) and rafts were observed in V–Fe alloys irradiated to 0.1 dpa. Voids were observed only within dislocation loops in both types of configurations. Ashby-Brown (AB) contrasts were always observed around voids, indicating that shell-like iron segregation with substantial elastic strain exists on the inner surface of the voids. For 1.17 dpa, swelling V–Fe alloys was always greater than those of un-alloyed vanadium, whatever the dislocation microstructures. Implication of a segregation shell in the swelling mechanism is discussed in addition to a model based on the dislocation bias.

Reduced activation ferritic steel is one of the leading structural material candidates for a nuclear fusion reactor, in which tungsten is introduced in order to improve the radiation resistance. Since the solute impurities have an effect on the embrittlement through segregation under irradiation, the stability of impurity elements should be elaborated. In the present study the segregation characteristics of tungsten and some general solute impurities in bcc iron were investigated nonempirically by first principles calculations, where the equilibrium segregation was considered via a regular solution model and the change in enthalpy for segregation were directly evaluated for comparison. Subsequently the energetic stabilities of impurity–impurity and impurity–vacancy pair were evaluated. The segregation enthalpy is influenced by the electronic interaction between the d-electron of Fe and the outer electron of the impurity element, and molybdenum and tungsten tend to prevent solute atoms from segregation.

Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn's disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV.Four groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period.(1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects characterized by a dose-dependent decrease in the level of a fibrosis-related growth factor (CTGF) in the early and mid-phases, irrespective of inflammation or changes in the TGF-β(1) level. Dose-dependent induction of apoptosis was noted in both fibroblasts and myofibroblasts from a relatively early stage.The results suggested that SIMV induces anti-fibrotic activity that is not directly involved in the anti-inflammatory effect from a relatively early stage the healing process of TNBS-induced colitis.

Root vigor is an important trait for the growth of terrestrial plants, especially in water-deficit environments. Although deserts plants are known for their highly developed root architecture, the molecular mechanism responsible for this trait has not been determined. Here we established an efficient protocol for the genetic manipulation of two varieties of watermelon plants: a desert-grown wild watermelon that shows vigorous root growth under drought, and a domesticated cultivar showing retardation of root growth under drought stress. Agrobacterium rhizogenes-mediated transgenic hairy roots were efficiently induced and selected from the hypocotyls of these plants. Transgenic GUS expression was detected in the roots by RT-PCR and histochemical GUS staining. Moreover, a liquid culture system for evaluating their root growth was also established. Interestingly, growth of the hairy roots derived from domesticated variety of watermelon strongly inhibited under high osmotic condition, whereas the hairy roots derived from wild variety of watermelon retained substantial growth rates under the stress condition. The new protocol presented here offers a powerful tool for the comparative study of the molecular mechanism underlying drought-induced root growth in desert plants.

Background and Aims: Various etiologies and diseases may be related to erosive and/or small ulcerative lesions without gross appearance in the colon during colonoscopy. However, few investigators report on differential diagnosis of colonic inflammatory diseases. Thus, we investigated the clinical significance of these lesions and the value of colonoscopy in the differential diagnosis of colitis. Methods: In 110 patients with erosive and/or small ulcerative lesions (

The size- and spacing- dependent obstacle strength due to the Cu precipitation in α-Fe is investigated by atomistic simulations, in which the effect on phase transformation of Cu precipitation is considered by a conventional self-guided molecular dynamics (SGMD) method that has an advantage to enhance the conformational sampling efficiency in MD simulations. A sequence of molecular statics simulations of the interaction between a pure edge dislocation and spherical Cu precipitation are performed to investigate the obstacle strength associated with phase transformation. It was shown that the SGMD method can accelerate calculating the bcc to 9R structure transformation of a small precipitate, enabling the transformation without introducing any excess vacancies. Such metallographic structures increase the obstacle strength through strong pinning effects as a result of the complicated atomic rearrangement within the Cu precipitation.

The same mutant allele of eukaryotic initiation factor 4E (eIF4E) that confers resistance to Pea seed-borne mosaic virus (sbm-1) and the white lupine strain of Bean yellow mosaic virus (wlv) also confers resistance to Clover yellow vein virus (ClYVV) in pea. The eIF4E genes from several pea lines were isolated and sequenced. Analysis of the eIF4E amino acid sequences from several resistant lines revealed that some lines, including PI 378159, have the same sequence as reported for sbm-1 and wlv. When eIF4E from a susceptible pea line was expressed from a ClYVV vector after mechanical inoculation of resistant PI 378159, the virus caused systemic infection, similar to its effects in susceptible line PI 250438. The resistance to ClYVV in line PI 378159 was characterized through a cross with PI 193835, which reportedly carries cyv-2. Mechanical inoculation of the F1 progeny with ClYVV resulted in no infection, indicating that the resistance gene in PI 378159 is identical to cyv-2 in PI 193835. Furthermore, particle bombardment of pea line PI 193835 with infectious cDNA of ClYVV (pClYVV/C3-S65T) resulted in the same resistance mode as that described for PI 378159. These results demonstrate that the resistance to ClYVV conferred by cyv-2 is mediated by eIF4E and that cyv-2 is identical to sbm-1 and wlv.

A combination of simulated annealing with Langevin molecular dynamics and the basin-hopping with occasional jumping (BHOJ) technique was used to systematically determine the most stable configurati...

A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.

In deciding upon a revegetation plan for ecosystem recovery of rock slope of mined-out quarry, it is necessary to evaluate the degree of ecosystem recovery from a viewpoint of an environmental impact assessment.Fundamental studies on evaluation of the degree of ecosystem recovery were carried out using revegetation simulation image with tree's height as an index of ecosystem recovery. First, the landscape evaluation experiments were carried out in the case of trees grow on the berm area only using revegetation simulation image with virtual reality system (VRS). Then the same experiments were carried out in case of tree growth on both berms and the slope area using revegetation simulation image with photomontage. Both experiments were carried out by using rating scale method. The main results obtained in this study are summarized as follows:1) In case of tree growth on the berm area, the degree of ecosystem recovery increases when height ratio increases. It became clear that the height ratio at the state of almost ecosystem recovery was 1.2. 2) In the case of tree growth on both berms and slope area, the degree of ecosystem recovery increase in proportion to height ratio. It became clear that the height ratio at the state of almost ecosystem recovery was 0.6. 3) In both cases, the degree of ecosystem recovery increases when height ratio increasess. 4) In the case of tree growth on both berms and the slope area, it is possible to shorten the length for ecosystem recovery compared to the tree growth on the berm area only.

It is well-known that the dislocation bias should be responsible for the large swelling. In V-Fe alloys, the extremely large swelling has been observed, which indicates that undersized Fe atoms must play a significant role for the modification of one-dimensional (1D) motion. In the present study, we performed molecular dynamics (MD) simulations with a newly constructed empirical potential based on the Finnis-Sinclair (FS) type embedded atom method (EAM) to investigate the effects of undersized Fe atoms on the static and dynamic properties of the interstitial migration under the strain field of several sizes of interstitial loops and an edge dislocation. The results show that the undersized Fe atoms tend to form a stable mixed-dumbbell configuration and the activation energy of migration towards a dislocation core is much lower than that of SIAs. Moreover, for V-Fe dumbbell the relative probability for intermediate configurations between 〈111〉-crowdion and 〈110〉-dumbbell below an edge dislocation core becomes significantly higher compared to that of V-V dumbbell. These results indicate that it is very likely that the continuous absorption of interstitial Fe atoms by a dislocation core would be possible and enhances the swelling in V-Fe alloys.

Background: Patients with ulcerative colitis (UC) exhibit an increased risk for the development of cancer of the colon and rectum. Cyclooxygenase (COX)-2 inhibitors are known to suppress sporadic colorectal cancer, but it is unknown whether selective COX-2 inhibitors exhibit a preventive effect in UC-associated neoplasia. This study investigated the preventive effect of nimesulide, a selective COX-2 inhibitor, on colorectal carcinogenesis in an experimental model of murine UC. Methods: Chronic colitis was induced in mice by administration of four cycles of dextran sulfate sodium (DSS) (each cycle: 5% DSS for 7 days and then distilled water for 14 days). The mice were killed 120 days after the completion of the fourth cycle. The mice were divided into the following five groups: group A served as a disease control; group B received a diet mixed with 400 p.p.m. of nimesulide during the whole period; group C received nimesulide during the four cycles of DSS administration (active phase); group D received nimesulide for 120 days from the end of the fourth cycle (remission phase); group E received no agents including DSS and served as a normal control. Results: The incidence of dysplasia and/or cancer was 28%, 15%, 11.8%, 6.7% and 0% in groups A–E, respectively. In group D, nimesulide significantly suppressed the occurrence of dysplasia and/or cancer (P

The rock slope of mined-out quarry is very bad condition for revegetation because it is steep and disturbed. However, in order to recover an ecosystem of mined-out quarry, it is necessary to create a plant growth base on the rock slope and allowing trees to grow.We carried out some fundamental studies on the plant growth base creation on the rock slope ,using forest top-soil. First, we researched the thickness of plant growth base and base soil properties at the site of the rock slope in the forest area. Then we carried out the stability of plant growth base soil on the rock slope by using plane slide stability analysis formula.The main results obtained in this study are as follows:1) The thickness of 10-15cm plant growth base soil is required in order for tree growth.2) In the conventional plane slide stability analysis, the thickness of base soil expressed by perpendicular thickness was changed into the method of expressing by actual thickness.3) The thickness of plant growth base which can be created on the base rock slope inclination of 60 degrees is 20cm.4) The cohesion of soil is indispensable for the plant growth base;if cohesion of the base soil is zero, we cannot create the plant growth base on the rock slope using this soil.

Crohn's disease (CD) is characterized by transmural inflammation of the gastrointestinal tract, which predisposes patients to the formation of a fistula. The efficacy of adalimumab (ADA) for an enterocutaneous fistula remains unclear. In this report, we present a case series of 3 patients with enterocutaneous fistulizing CD treated with ADA. ADA treatment achieved sustained complete fistula closure in one patient. The other two cases, which failed to achieve fistula closure, had intestinal stenosis and were not receiving concomitant azathioprine. Combination therapy with ADA and azathioprine may be a useful option and an alternative to surgery for enterocutaneous fistulizing CD.

Association behavior and physical gelation mechanism of ABA triblock copolymer dissolved in B-selective solvent have been studied systematically from dilute to moderately concentrated solutions. Static and dynamic light scattering and nuclear magnetic resonance measurements for dilute solutions of poly(methyl methacrylate)-block-poly(tert-butyl acrylate)-block-poly(methyl methacrylate) (PMMA – Pt BuA – PMMA) in 1-butanol (Pt BuA selective solvent) indicated that PMMA– Pt BuA – PMMA chains are molecularly dissolved above 50 8C. With decreasing temperature, the triblock copolymers form associated micelles consisting PMMA associated core and Pt BuA shell. Linear dynamic viscoelastic measurements for solutions with moderate concentration (3.9– 12.0 wt%) revealed that the system was viscous sol state at 60 8C. Drastic increase of shear storage modulus ðG 0 Þ occurred with decreasing temperature, and at 25 8C, G 0 showed rubbery plateau with weak frequency dependency, means the formation of elastic physical gel. The consistency between the temperature for micelle formation and that at the increase in G 0 indicates that the physical gelation is owing to the network formation as the result of the association of PMMA chains and the bridging Pt BuA chains connecting the PMMA cores. Master curves for the dynamic moduli were derived by time – temperature superposition along the frequency axis. Just above sol –gel transition concentration ðCgelÞ; the master curves suggest the existence of fairy amount of aggregate that is not incorporated in the macroscopic network. With the increase in polymer concentration, the master curves become to reveal Maxwell-type viscoelasticity with narrow relaxation time distribution, suggesting the formation of transient network with easily generation and destruction of crosslinks. Concentration dependency of the plateau modulus is stronger than the theoretically expected, means the macroscopic transient network grows with polymer concentration by increasing the fraction of elastically effective bridging Pt BuA chain above Cgel: q 2003 Elsevier Ltd. All rights reserved.

Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. GGA protects a variety of cells and tissues against numerous stresses via induction of heat shock protein (HSP) 70, and it has recently been reported to protect mice from experimental ulcerative colitis (UC). However, it is unknown whether GGA exhibits a preventive effect on UC-associated neoplasia. In the present study, we evaluated the preventive effects of GGA on colitis-related carcinogenesis in the mouse colon. Mice were administered 1,2-dimethylhydrazine (DMH) subcutaneously three times within a week, followed by 2 cycles of dextran sulfate sodium (DSS) (each cycle, 3% DSS for 7 days and then distilled water for 14 days) and they were sacrificed 28 days after the completion of the 2 cycles. The mice were divided into the following groups according to the diet received during the experiment: group A, which received a standard diet and served as a disease control; group B, which received a diet mixed with 0.25% GGA; group C, which received a diet mixed with 0.5% GGA; group D, which received a diet mixed with 1.0% GGA; group E, which received a diet mixed with 2.0% GGA; and group F, which received a diet containing no agents, including DSS and served as a normal control. The incidence of neoplasia was assessed. The expression of inducible nitric oxide synthase (iNOS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also determined. In addition, the expression of HSP70 in the colon tissues was determined by immunohistochemistry and western blot analysis. The mean number of tumors was 16.6, 11.0, 9.4, 5.8, 5.4 and 0 in groups A-F, respectively. GGA significantly suppressed the occurrence of neoplasia in a dose-dependent manner. GGA treatment enhanced the expression of HSP70 and suppressed the oxidative damage in the background mucosa (i.e. lesion-free colon). These results suggest that GGA could be useful in the prevention of UC-associated neoplasia.

Luminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition.Intestinal injury was induced in mice by administration of dextran sulfate sodium (DSS) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR5 agonist betulinic acid (BTA) and the DPPIV inhibitor sitagliptin phosphate monohydrate (STG) were administered orally for 7 days. Male C57BL/6 mice (6-7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15 mg/L BTA), BTA high group (50 mg/L BTA), and BTA high + STG (3 mg/kg, i.g.) group.The selective TGR5 agonist BTA dose-dependently suppressed disease activity index and mRNA expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the colon. Nevertheless, STG administration had little additive effect on BTA-induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS-treated mice with increased mucosal DPPIV. Co-administration of the selective GLP-2 antagonist GLP-2 (3-33) reversed the effect of BTA.The selective TGR5 agonist BTA ameliorated DSS-induced colitis in mice via the GLP-2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP-2 degradation.

Background Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. Methods Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment. Results There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p Conclusion Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole. Trial registration This study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114)

AIM: To assess adalimumab’s efficacy with concomitant azathioprine (AZA) for induction and maintenance of clinical remission in Japanese Crohn’s disease (CD) patients. METHODS: This retrospective, observational, single-center study enrolled 28 consecutive CD patients treated with adalimumab (ADA). Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn’s disease activity index (CDAI) and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered: 160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS: The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION: Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn’s disease patients.