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Background: The new curcumin derivative, Theracurmin® has a 27-fold higher absorption rate than the natural curcumin powder. Its pharmacologic actions include inhibition of the nuclear factor NF-κB, known to mediate the expression of inflammatory cytokines. We were interested to evaluate efficacy of Theracurmin® in patients with Crohn's disease (CD). Methods: Theracurmin® (360mg/day, n=20) or placebo (n=10) was administered to patients with active mild to moderate CD for 12 weeks. Efficacy assessment included clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. Findings: In the Theracurmin® group, significant reduction of clinical disease activity was observed at 12 weeks relative to week 0 (P=0.005). The clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, significantly higher than in the placebo group (P=0.033, P=0.020, and P=0.020). Further, in the Theracurmin® group, significant healing of anal lesions (P=0.017) and endoscopic CD severity (P=0.032) were observed at weeks 8 and 12, respectively, relative to week 0. However, the mucosal healing rate at week 12 in the Theracurmin® group was 15.0%. No serious adverse event was observed in either group throughout our observation time. Interpretation: In this study, Theracurmin® in patients with active mild to moderate CD produced significant clinical and endoscopic efficacy together with a favourable safety profile. Trial registration: UMIN000015770 Funding Statement: Theracurmin® was a gift from Theravalues Corporation, Tokyo, Japan. The authors received no external funding for this study. Declaration of Interests: All authors acknowledge having no conflict of interest in connection with the publication of this manuscript. Ethics Approval Statement: At each institution, the study protocol was reviewed and approved by the committee on the Ethics of Clinical Trials involving human subjects. Further, the trial was conducted by adherence to the principles of Good Clinical Practice (GCP) and the ethical standards laid down in the 1964 Helsinki Declaration and its subsequent amendments. Similarly, informed consent was obtained from all patients after explaining the purpose of the study and the nature of the procedures involved.

The crystalline morphology formed in binary blends of poly(e-caprolactone)- block -polyethylene (PCL- b -PE) copolymers and PCL homopolymers has been examined using synchrotron small-angle X-ray scattering (SR-SAXS) and differential scanning calorimetry (DSC) as a function of the homopolymer fraction in the blend. The PE block crystallized first on quenching from a lamellar microdomain structure to set a hard lamellar morphology (PE lamellar morphology) in the blend, followed by the crystallization of PCL chains ( i.e ., PCL homopolymers + PCL blocks). Two binary blends were studied by considering the miscible state of PCL homopolymers in the microdomain structure: when the PCL homopolymers were uniformly mixed with PCL blocks, they formed a mixed crystal. When the PCL homopolymers were localized between PCL blocks in the microdomain structure, DSC results suggested the possible formation of separate PCL crystals in the PE lamellar morphology. The effect of the advance crystallization of PE blocks on the subsequent crystallization of PCL chains was discussed as compared with the crystalline morphology formed in PCL- block -polybutadiene copolymer/PCL homopolymer blends, where the crystallization of PCL chains started directly from a microdomain structure without forming the hard lamellar morphology.

Statins, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are known not only as cholesterol-lowering agents but also as anti-inflammatory mediators. However, their regulatory effect on intestinal mucosal immunity remains unclear. The present study examined the possible direct effects of statin on intestinal intraepithelial lymphocytes (IELs), the front line cells of the intestinal mucosal immune system. Murine IELs were isolated from the small intestines of C57BL/6 mice. IELs activated with anti-CD3/CD28 monoclonal antibodies produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-4 in significant numbers; however, they did not produce IL-5. Both simvastatin and lovastatin suppressed IEL production of IFN-γ, TNF-α, IL-2, and IL-4 in a dose-dependent manner, whereas 48-h treatment with high concentrations (5 × 10(-5)M) of simvastatin and lovastatin did not affect the number of IELs. The suppressive effect of the simvastatin was significantly restored by the addition of mevalonate, farnesyl pyrophosphate ammonium salt, and geranylgeranyl pyrophosphate ammonium salt, which are downstream metabolites of HMG-CoA. These findings suggest that statins have direct suppressive effects on the production of T helper 1-cytokines and IL-4 in IELs; these effects are associated with inhibition of the mevalonate pathway to some extent.

We examined whether norepinephrine (NE) had direct effects on cytokine production by murine intestinal intraepithelial lymphocytes (IELs), compared with splenocytes. CD3⁺ IELs and CD3⁺ splenocytes expressed α(1B), α(1D), α(2C), β₁, β₂, and β₃ adrenoceptors (ARs). NE significantly suppressed IFN-γ and TNF-α production by IELs and splenocytes ex vivo. The suppressive effects of NE in IELs were reversed by β₁ AR antagonist CGP-20712A, whereas those in splenocytes were reversed by β₂ AR antagonist ICI118,551. In IELs, β₁ AR agonist xamoterol mimicked the suppressive effects of NE. These results indicated NE regulates intestinal mucosal immune responses mediated by IELs via β₁ AR.

Super-hydrophobic surface has been prepared onto biodegradable polymer by a combination of transcribing microscopic structure of a water-repellent leaf and a chemical treatment. An aroid leaf has been chosen for the preparation of the super-hydrophobic surface since the leaf has concavity microscopic structure, which is easy to handle for a material use. The microscopic pattern was transcribed onto poly(e-caprolactone) (PCL) sheet by using replica method, then it was further treated by soaking in a mixture of acetone/methanol solution. The resultant PCL having the microscopic concavity pattern showed high water contact angle of 148° and also showed antibacterial property for filamentous fungi.

The conditions for molecular orientation of electrochemically synthesized polythiophene have been investigated. The polymer chains are preferentially oriented along the film surface direction, i.e. parallel to the electrode surface, under conditions of (a) polymerization around the freezing point of the solvent used in the electrolyte, and (b) polymerization at low current density (below 1 mA/cm 2 ) around the oxidation potential of the monomer. The polymerizations were also carried out in a magnetic field. Under a magnetic field parallel to the electrode surface, the polythiophene chain oriented itself along the electrode surface even at a higher current density of 2 mA/cm 2 . On the other hand, a magnetic field perpendicular to the electrode surface inhibited the molecular orientation, even under the conditions of (a) and (b).

The anisotropy in mechanical properties of forged isotactic polypropylene (iPP) has been investigated by microhardness indentation and Izod impact tests. The results are important, since the major changes in these properties that have been found can influence the growing number of applications where iPP is indented or impacted in use. The iPP had a molecular weight of 2.9 × 10 5 and an initial fraction of 64% α-crystal. For these samples forged at 140°C (resulting in α-crystal only plus amorphous), the indentation hardness perpendicular to the plane direction, H (⊥), slightly increased with draw. The hardness tested parallel to the film surface, H (/ t |), decreased rapidly with draw. For the sample forged at 50°C (containing draw-generated smectic), both H (/ t |) and H (⊥) decreased with draw, suggesting the softness of the smectic phase. The anisotropy, H (⊥)/ H (/ t |), for samples forged at 50°C is higher than that for samples forged at 140°C at a comparable compression ratio ( CR ), e.g. at CR = 7.5, H (⊥)/ H (/ t |) for 50°C and 140°C are 2.7 and 2, respectively. The impact strength of forged iPP was very different from the results of the indentation test. For samples forged at 50 and 140°C, the strength both parallel and perpendicular to the forged sample surface increased strongly with draw. The strength tested along the planar direction is about twice that tested through the thickness direction. Testing in each direction broke the samples into layers. The mechanism of energy absorption is closely related to the morphology-developed planar orientation with the crystal b -axis orientation normal to the plane direction.

The phase structures of uniplanar-drawn isotactic polypropylene (iPP) have been investigated. Three phases (α-crystal, smectic and amorphous) are found to coexist in the uniaxially compressed samples. From thermal analyses and density measurements, the fractions and densities of these phases have been evaluated. At a compression draw temperature of 50°C Ts, decrystallization without smectic phase stability proceeded during the deformation. No draw-induced crystallization was observed. At all deformation temperatures, the density of the amorphous phase increased in the initial stage of deformation reaching a limit on further draw.

Isotactic polypropylene (iPP) ( M w = 2.9 × 10 5 ) has been deformed in uniaxial compression by forging at several constant temperatures from 20 to 140°C. A relation between draw efficiency and the formation of the smectic phase during deformation has been examined over a wide range of compression draw ratios (∼50). At a forging temperature below the smectic-phase stability limit temperature ( T s ), the efficiency of draw, parallel to the uniplanar direction, was high (∼97%) and independent of the compression ratio, pressure and draw temperature ( T d ). The relation between the compression yield energy ( E y ) and T d has also been examined. E y , the area under the compressive stress-strain curve up to the yield point, as a function of T d was found to consist of two linear components of different slope. These two linear relations arose from the glassy and crystalline phases. The intercept temperature ( T i ) at zero yield energy for the glassy phase has been evaluated to understand compression drawability. Above T i , the achievable compression ratio ( CR ) increased steadily with T d . At a given T d , the CR increased with increasing applied pressure, and this tendency was more prominent above T i . The T i moved higher as the compression rate was increased.1

Isotactic polypropylene was uniaxially compressed by a forging (uniplanar) process. The physical properties and morphology of the compressed samples were investigated by means of mechanical tests, trirefringence measurement and microscopy. Four major effects of planar deformation on the physical properties and morphology were observed. (1) The glass transition temperature of the compressed sample (evaluated from dynamic mechanical analysis) increased with draw. (2) The smectic phase induced by the compression draw increased sample transparency. (3) Both tensile modulus and strength parallel to the uniplanar direction increased with draw. The smectic phase generated, however, reduced the tensile modulus with no significant effect on tensile strength. (4) The compressed samples possessed a layered structure which was developed by the flattening of the original spherulites.

The relation between molecular weights and electrical properties was investigated for electrochemically prepared poly(3-hexylthiophene) (PHT). The PHT films with weight-average molecular weight (Mw) in the range 12 500–58 000 were prepared by controlling the polyerization conditions. For Mw 25 000, the increase in σ with Mw was minor. The visible absorption maximum ( π−π∗ absorption band) of the neutral PHT films shifted to the red side as Mw increased. The shift was more prominent in the samples with low Mw (

Notes. †Participants were asked to rate symptom improvement on the Global Impression of Change scale ranging from 1 (substantially improved) to 7(substantially worse) at posttreatment. ‡Higher scores on the Tellegen Absorption Scale represent a higher degree of hypnotic ability. §Higher scores are indicative of better perceived health and functioning for the PCS and MCS. ¶QOLRAD, Quality of Life in Reflux and Dysphagia. Lower score indicates more severe impact of symptoms on daily functioning. ††Lower score on the VSI represent greater symptom related anxiety. ‡‡Higher score indicates greater heartburn symptom catastrophizing. *statistically significant. PPI, proton pump inhibitor; Pre, Pretreatment; Post, Post-treatment; PCS, physical component summary; MCS, mental health component summary

Background: Potent neutralization of intragastric pH is important in the treatment of acidrelated diseases such as peptic ulcers and gastroesophageal reflux disease (GERD). However, once (o.i.d.)or twice (b.i.d.)-daily dosing of a standard dose of proton pump inhibitors (PPIs) does not always provide sufficient acid inhibition over a 24-h period, particularly for rapid metabolizers (RMs) of CYP2C19. We previously reported that esomeprazole (b.i.d.) exerts [check] potent acid inhibition in CYP2C19 RMs compared to omeprazole, lansoprazole, and rabeprazole, and that complete inhibition of gastric acid secretion in all patients is difficult. Although rabeprazole (10 mg, q.i.d.) and lansoprazole (30 mg, q.i.d.) reportedly induce sufficient acid inhibition in CYP2C19 RMs, whether or not esomeprazole (20 mg, q.i.d.) can induce sufficient inhibition over a 24-h period in RMs remains unclear. We therefore examined the efficacy of esomeprazole q.i.d. in achieving sufficient acid inhibition. Methods: In a randomized cross-over study, 30 healthy, Helicobacter pylori-negative, young Japanese volunteers (10 RMs, 10 intermediate metabolizers [IMs], and 10 poor metabolizers [PMs] of CYP2C19) received esomeprazole 20 mg b.i.d. or q.i.d. for 1 week. Intragastric pH monitoring was performed on Day 7. Intragastric pHs were also compared to esomeprazole 20 mg q.i.d. and rabeprazole 10 mg q.i.d. (13 RMs, 15 IMs and 7 PMs). Data from 24-h pH monitoring from our previous study of the efficacy of rabeprazole 10 mg q.i.d was used for comparison. Results: Median pH attained with esomeprazole 20 mg b.i.d. differed

Background: Although current standard first-line treatment to eradicate Helicobacter pylori is triple therapy combining a proton pump inhibitor with two antibiotics (mainly clarithromycin and amoxicillin or metronidazole), there is increasing tendency to alter this treatment. Cure rates with first-line 14-day triple therapy in the geographic area including our country can barely reach 45-50%. Modification of standard first-line treatment by adding bismuth subcitrate has been suggested to increase this relatively low cure rates. Aim: The aim of this study was to assess efficacy of adding product containing several probiotic strains as an adjuvant to modified first-line treatment to eradicate H.pylori. Materials and Methods: An open label observational clinical study was designed to compare two patient groups receiving modified triple therapy and bismuth subcitrate (Group 1, n=100) with a regimen consisting of modified triple therapy and bismuth subcitrate plus concomitant NBL probiotic added at the same time (Group 2, n=150). In Group 1, patients were given a 14-day treatment program consisting of lansoprazole 40 mg (b.i.d.), amoxicillin 1 gr (b.i.d.), clarithyromycin 500 mg (b.i.d) and colloidal bismuth subcitrate 300 mg (2 tablets before breakfast and dinner). In Group 2, NBL probiotic (active probiotics: Lactobacillus acidophilus, Enterococcus faecium, Lactobacillus plantarum, Bfidobacterium lactis, Streptococus thermophilus, Bfidobacterium longum, 1.5 x 109 cfu/chewable tablet) tablets (b.i.d) for 14 days was given in addition to the same modified first-line treatment used for Group 1. Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. Results: In Group 1, 89 patients were available for follow up and 69 patients eradicated H.pylori. In Group 2, 134 patients were available for follow up and 120 patients eradicated H.pylori. Per protocol and intention to treat eradication rates were 77.5% and 69.0%, respectively for Group1 and were 89.6% and 80,0% respectively for Group 2. Adding NBL probiotic to triple therapy and bismuth subcitrate has led to a statistically significant more successful eradication rates in both PP and ITT analyses (x2 test: P