FRAX score and recent fall history predict the incidence for sarcopenia in community-dwelling older adults: a prospective cohort study.

We hypothesized that the baseline FRAX score and previous falls would predict the incidence of sarcopenia in community-dwelling older adults who received medical check-ups. The FRAX score (hazard ratio [HR] = 1.087, 95% CI 1.014-1.167) and previous falls (HR = 5.181, 95% CI 1.002-26.777) were determined to be independent risk factors for the incidence of sarcopenia. PURPOSE: This prospective study was performed to elucidate the prevalence and incidence of sarcopenia in community-dwelling older adults who received medical check-ups, and to determine whether FRAX score and fall history predict the incidence of sarcopenia. METHODS: Participants were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. Study inclusion criteria were aged older than 60 years, living independently, and ability to walk without assistance. Individuals who received nursing care were excluded from the study. A total of 426 residential participants were analyzed. Demographic information, fall history of the previous year, and FRAX score without bone mineral density were assessed. The assessment for sarcopenia was based on the recommendations of the Asian Working Group for Sarcopenia. RESULTS: The final sample for the assessment of sarcopenia incidence comprised 258 participants. The mean follow-up time was 2.92 years. The rate of sarcopenia was 1.06 cases per 100 person-years at risk. The Cox multivariate logistic regression model in our analysis was adjusted for age, gender, muscle mass, and covariates and showed that the FRAX score (HR = 1.087, 95% CI 1.014-1.167) and recent history of falls (HR = 5.181, 95% CI 1.002-26.777) were independent risk factors for the incidence of sarcopenia. CONCLUSION: FRAX and history of falling can be a simple screening tool to raise awareness of the prevention of osteoporosis and sarcopenia in clinical settings.

Effect of interlamellar interactions on shear induced multilamellar vesicle formation.

Shear-induced multilamellar vesicle (MLV) formation has been studied by coupling the small-angle neutron scattering (SANS) technique with neutron spin echo (NSE) spectroscopy. A 10% mass fraction of the nonionic surfactant pentaethylene glycol dodecyl ether (C12E5) in water was selected as a model system for studying weak inter-lamellar interactions. These interactions are controlled either by adding an anionic surfactant, sodium dodecyl sulfate, or an antagonistic salt, rubidium tetraphenylborate. Increasing the charge density in the bilayer induces an enhanced ordering of the lamellar structure. The charge density dependence of the membrane bending modulus was determined by NSE and showed an increasing trend with charge. This behavior is well explained by a classical theoretical model. By considering the Caillé parameters calculated from the SANS data, the layer compressibility modulus B¯ is estimated and the nature of the dominant inter-lamellar interaction is determined. Shear flow induces MLV formation around a shear rate of 10 s-1, when a small amount of charge is included in the membrane. The flow-induced layer undulations are in-phase between neighboring layers when the inter-lamellar interaction is sufficiently strong. Under these conditions, MLV formation can occur without significantly changing the inter-lamellar spacing. On the other hand, in the case of weak inter-lamellar interactions, the flow-induced undulations are not in-phase, and greater steric repulsion leads to an increase in the inter-lamellar spacing with shear rate. In this case, MLV formation occurs as the amplitude of the undulations gets larger and the steric interaction leads to in-phase undulations between neighboring membranes.

Low programmed cell death-1 (PD-1) expression in peripheral CD4(+) T cells in Japanese patients with autoimmune type 1 diabetes.

Programmed cell death-1 (PD-1) is a co-stimulatory molecule that inhibits T cell proliferation. We aimed to clarify PD-1 expression in CD4(+) T cells and the association between PD-1 expression and the 7785C/T polymorphism of PDCD1, with a focus on the two subtypes of type 1 diabetes, type 1A diabetes (T1AD) and fulminant type 1 diabetes (FT1D), in the Japanese population. We examined 22 patients with T1AD, 15 with FT1D, 19 with type 2 diabetes (T2D) and 29 healthy control (HC) subjects. Fluorescence-activated cell sorting (FACS) and real-time PCR were utilized to analyse PD-1 expression quantitatively. Genotyping of 7785C/T in PDCD1 was performed using the TaqMan method in a total of 63 subjects (21 with T1AD, 15 with FT1D and 27 HC). FACS revealed a significant reduction in PD-1 expression in CD4(+) T cells in patients with T1AD (mean: 4.2 vs. 6.0% in FT1D, P=0.0450; vs. 5.8% in T2D, P=0.0098; vs. 6.0% in HC, P=0.0018). PD-1 mRNA expression in CD4(+) T cells was also significantly lower in patients with T1AD than in the HC subjects. Of the 63 subjects, PD-1 expression was significantly lower in individuals with the 7785C/C genotype than in those with the C/T and T/T genotypes (mean: 4.1 vs. 5.9%, P=0.0016). Our results indicate that lower PD-1 expression in CD4(+) T-cells might contribute to the development of T1AD through T cell activation.

Safety and Feasibility of a Pancreaticoduodenectomy with Total Meso-Pancreatoduodenum Excision: Analysis in Various Periampullary Disorders.

BACKGROUND/AIMS: This study aimed to evaluate the safety and feasibility of a pancreaticoduodenectomy with total meso-pancreatoduodenum excision (tMPDe) as an new anatomical concept. METHODOLOGY: A total of 90 patients underwent PD for various periampullary diseases. Of these, 52 patients received a conventional PD (cPD), while 38 patients underwent a tMPDe. Surgical outcomes were compared between the two study groups. RESULTS: Operative time was equivalent in the two groups; however, the estimated blood loss (cPD, 1360 ml; tMPDe, 995 ml; median, P = 0.026) and blood transfusion rate (cPD, 63%; tMPDe, 31% ; P = 0.001) were significantly decreased in tMPDe. Morbidity had no significant difference between cPD and tMPDe, and tMPDe showed no characteristic complications. With regard to oncological aspects, tMPDe was superior to cPD. Risk factors analysis revealed the operative time (P = 0.003), estimated blood loss (P < 0.001), and blood transfusion (P < 0.001) to be significant predictive risk factors for postoperative morbidity but not tMPDe procedure (P = 0.794). CONCLUSIONS: tMPDe is safe and superior to cPD because it is a bloodless operation with a good oncological outcome: We concluded that tMPDe should be adaptable to various periampullary diseases, including benign and low-grade malignant disorders.

The effect of spine postures on the hydrodynamic drag in Epinephelus ongus larvae.

Laboratory behavioural observation and computational fluid dynamics (CFD) analysis were conducted to examine whether the movement of the elongated dorsal and pelvic spines changed the hydrodynamic drag in white-streaked grouper Epinephelus ongus larvae. The behavioural observation in the tank revealed that the larvae extended the dorsal and pelvic spines during passive transport and retracted during swimming; the angles of the dorsal and pelvic spines in relation to the anteroposterior axis were larger during the passive transport (mean ± S.D. = 28.84 ± 14.27 and 20.35 ± 15.05°) than those during the swimming (mean ± S.D. = 2.59 ± 5.55 and 0.32 ± 6.49°). The CFD analysis indicated that the relative hydrodynamic drag acting on the larvae was approximately 1.25 times higher when the spines were extended (passive transport) than when the spines were retracted (swimming), suggesting that the E. ongus larvae have an ability to adjust their hydrodynamic drag depending on the behavioural context.

Distal pancreatectomy utilizing a flexible stapler closure eliminates the risk of pancreas-related factors for postoperative pancreatic fistula.

OBJECTIVES: To identify the risk factors for clinically relevant pancreatic fistula after distal pancreatectomy with a flexible cartridge stapler, TL60. METHODS: Forty consecutive patients who underwent a distal pancreatectomy by the TL60 stapler were retrospectively reviewed in association with postoperative complications. RESULTS: The overall morbidity rate was 43% (17 patients), and mortality was null. Pancreatic fistula was the most frequent postoperative complication, seen in 11 patients (27.5%): grade A in 4 (10%) and grade B in 7 (17.5%). No grade C pancreatic fistula was observed. Univariate analyses of risk factors demonstrated that pancreas-related factors, including diabetes mellitus, thickness and texture of the pancreatic parenchyma, transection line for the pancreas, pancreatic duct ligation, and use of artificial patches had no impact on the occurrence of pancreatic fistula. A multivariable logistic regression analysis identified operative time (≥ 300 min) as the only notable predictor of clinically relevant pancreatic fistula (odds ratio = 3.253, 95% confidence interval 1.739-5.752; p = 0.031). CONCLUSION: Distal pancreatectomy with the use of the TL60 stapler eliminated the risk of pancreas-related factors for the occurrence of clinically relevant pancreatic fistula.

Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome.

The outcome and cause of death of each lung disease directly associated with rheumatoid arthritis (RA-LD) have been poorly investigated. A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up period after the initial visit for a respiratory examination was 4.5 yrs. A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of patients with UIP was worse than that of patients with NSIP.

Effects of a tropical cyclone on the distribution of hatchery-reared black-spot tuskfish Choerodon schoenleinii determined by acoustic telemetry.

The effects of a tropical cyclone on the distribution of hatchery-reared black-spot tuskfish Choerodon schoenleinii were examined using acoustic telemetry. Nine fish were released in Urasoko Bay, Ishigaki Island, Japan, in September 2006, and another nine were released in June to July 2007, before a cyclone's passing through the area in September 2007. Data for the fish released in 2006 were used as the cyclone-inexperienced group to compare their distribution pattern to that of the 2007 cyclone-experienced group. Both groups of fish were monitored for up to 150 days. Of the nine fish in each group, four (44%) and two (22%) were monitored for over 150 days in the cyclone-inexperienced and the cyclone-experienced groups, respectively. Three of the five fish that had settled in the monitoring area left the area within a few days of the cyclone event. To estimate the time of disappearance of the fish, maximum wind speed during a period of 7 days (indicating the occurrence and intensity of the tropical cyclone), fish size and release year were evaluated as explanatory variables using a Cox proportional hazards model with Akaike's information criterion. The best predictive model included the effect of maximum wind speed. One fish that left the monitoring area displayed movement patterns related to strong winds, suggesting that wind-associated strong currents swept the fish away. No relationships were found between the movement patterns of the other two fish and any physical environmental data. The daily detection periods of one of the two fish gradually decreased after the cyclone hit, and this fish eventually left the monitoring area within 3 days, suggesting that it shifted to a habitat outside the monitoring area. These results indicate that tropical cyclones have both direct and indirect effects on the distribution of hatchery-reared C. schoenleinii.

Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset.

AIM/HYPOTHESIS: We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive. METHODS: We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA. RESULTS: DRB1*0405-DQB1*0401, DRB1*0802-DQB1*0302 and DRB1*0901-DQB1*0303 were associated with acute-onset type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 genotype achieving the highest odds ratio of 42.7. DRB1*1501-DQB1*0602 and DRB1*1502-DQB1*0601 were negatively associated with acute-onset type 1 diabetes. A similar tendency was observed for slowly progressive type 1 diabetes. In contrast, only DRB1*0405-DQB1*0401 was associated with fulminant type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0405-DQB1*0401 genotype showing the highest odds ratio of 11.2. DRB1*0802-DQB1*0302, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 and DRB1*1501-DQB1*0602 were not associated with fulminant type 1 diabetes. The association of class I alleles and a panel of SNPs in an extended HLA region with fulminant type 1 diabetes was also different from that seen for the acute-onset and slowly progressive forms. The presence of both one and two susceptible haplotypes conferred susceptibility to slowly progressive type 1 diabetes, whereas the presence of two susceptible haplotypes was required to confer susceptibility to acute-onset and fulminant type 1 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that HLA associations with fulminant type 1 diabetes are qualitatively different from those with other subtypes of type 1 diabetes, whereas the HLA contribution to slowly progressive type 1 diabetes is qualitatively similar to, but quantitatively different from, that in acute-onset type 1 diabetes.

Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia.

AIMS: Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease. METHODS AND RESULTS: Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case. CONCLUSIONS: BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course.

AIMS: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking-related interstitial lung disease. METHODS AND RESULTS: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P < 0.01) with lower lobe predominance. There were significant correlations (P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone (P < 0.01). CONCLUSIONS: AEF is an important smoking-related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important.

Seasonal and spatial variations in characteristics of Lake Biwa dissolved organic matter: sorption of pyrene and its derivatives and fluorescence properties.

The objectives of this research were to investigate seasonal and spatial variations in (1) sorption of pyrene and its derivatives onto dissolved organic matter (DOM) and (2) fluorescence properties of DOM in Lake Biwa, Japan. In the case of pyrene, sorption coefficient (Kdoc) of Lake Biwa DOM seasonally changed from 1,200 to 3,800 L/kgC. Vertical distribution of Kdoc was affected by thermocline formation in summer, while it was uniformly distributed as a result of vertical mixing in winter. Functional groups affected sorption of pyrene onto Lake Biwa DOM in different manner from that onto Suwannee River fulvic acid. Three-dimensional excitation emission matrices (3D-EEMs) fluorescence spectroscopy was applied to characterize Lake Biwa DOMs and indicated the existence of at least two fluorophores. The two major peaks at Ex230/Em300 and Ex230/Em425 originated from protein-like and fulvic/humic-like substances, respectively. The peak at Ex230/Em300 showed the maximum fluorescence intensity at a depth of 5 m and could be affected by stratification of the water column in summer. On the other hand, the peak at Ex230/Em425 showed similar profiles both in summer and in winter. These results demonstrably showed that sorption of micropollutants and fluorescence properties of Lake Biwa DOMs were seasonally and spatially varied.

Expression of isotocin is male-specifically up-regulated by gonadal androgen in the medaka brain.

Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioural processes, ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologues in other animals. In the present study, we show that, in the teleost fish, medaka (Oryzias latipes), the expression of the isotocin gene (it), the teleost orthologue of Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic nucleus) is male-specifically up-regulated by gonadal androgen, whereas it expression in the magnocellular/gigantocellular preoptic nuclei (homologous to the mammalian paraventricular nucleus) is independent of sex steroids in both sexes. None of the it-expressing neurones appear to co-express androgen receptors, suggesting that the effect of androgen on it expression is indirect. We found that the expression of a kisspeptin gene, kiss2, in the male brain is dependent on gonadal androgen, raising the possibility that the androgen-dependent expression of it may be mediated by kiss2 neurones. Our data also show that the isotocin peptide synthesised in response to androgen is axonally transported to the posterior pituitary to act peripherally. Given that levels of it expression are higher in females than in males, androgen may serve to compensate for the female-biased it expression to ensure a role for isotocin that is equally important for both sexes. These results are unexpectedly quite different from those reported in rodents, indicating that the regulatory role of sex steroids in Oxt/it expression has diverged during evolution, possibly with accompanying changes in the role of oxytocin/isotocin.

Preferential expression of immunoreactive fucosylceramide in adenocarcinoma of the lung.

The expression of fucosylceramide (PC47H antigen) in 97 lung cancers and 4 extrapulmonary squamous cell carcinomas was examined with the use of a novel monoclonal antibody, PC47H, recognizing fucosylceramide specifically. The observed variation in fucosylceramide content was dependent on the degree of glandular differentiation in adenocarcinoma of the lung. Fucosylceramide was abundantly expressed in well differentiated adenocarcinoma of the lung and poorly expressed in poorly differentiated adenocarcinoma. Some squamous cell carcinomas of the lung reacted with this monoclonal antibody weakly, but the reaction was noted only at the periphery of the epithelial sheets. Extrapulmonary squamous cell carcinoma and small-cell carcinomas did not react with monoclonal antibody PC47H. Interestingly, large cell carcinomas of uncertain cell origin were all positive for fucosylceramide, which accumulated in the cytoplasm. At the ultrastructural level, fucosylceramide was located in the plasma membrane and unit membrane of the rough endoplasmic reticulum. On the other hand, carcinoembryonic antigen as an adenocarcinoma-associated tumor marker was expressed significantly in squamous cell carcinomas as well as adenocarcinomas. Taken together, fucosylceramide seems to be expressed preferentially in adenocarcinomas, and is closely linked to glandular differentiation. Thus it may be a better tumor marker than carcinoembryonic antigen.

Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide.

Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.

Identification of a novel gene marker specific for epithelial cells by utilizing a 3'-directed cDNA library.

To achieve reliability of molecular diagnosis using reverse transcription-PCR (RT-PCR), we established a unique method to search for a novel gene marker specific for colonic epithelial cells. Of eight candidate genes selected from a 3'-directed cDNA library in colonic mucosa, two genes were expressed in normal mucosa and cancer of the colon but not in either normal lymph node or normal liver tissue. Known sequences of these genes were reported to be located in the 3' noncoding region, and an additional sequence just upstream to gs04094 (one of the candidate genes) was determined. According to the newly identified sequence, we designed a new set of primers so that we could distinguish the DNA fragment amplified in RT-PCR from that in genomic PCR. RT-PCR using these primers demonstrated that gs04094 was expressed in all of 10 primary colon cancers and 4 liver metastases from colon cancer but in none of 5 normal lymph nodes, 10 peripheral blood samples, and 2 normal liver tissues. Sensitivity of this method was so high as to detect gs04094 mRNA in 10(-6) microg of colon cancer RNA per 1 microg of normal lymph node RNA. Thus, our strategy to search for a novel gene marker using 3'-directed cDNA library proved to be highly efficient.

Modified total meso-pancreatoduodenum excision with pancreaticoduodenectomy as a mesopancreatic plane surgery in borderline resectable pancreatic cancer.

BACKGROUND: A superior mesenteric artery (SMA)-first approach has been considered to be an efficient technique in pancreaticoduodenectomy when the SMA is a factor of borderline resectable pancreatic head cancer (BRPHC). However, this excellent procedure has limitations in terms of tumor resection with an intact coverage including the pancreatic tumor and the tumor-draining lymphovascular systems and the ability to achieve a complete regional lymphadenectomy. METHODS: A modified mesenteric plane procedure has been developed that provides improved regional lymphadenectomy and permits adjustment of the surgical approach, which is based on the direction of the tumor infiltration. RESULTS: Of 55 patients taken to surgery, 19 had peritoneal dissemination and/or liver metastasis at staging laparoscopy, and the procedure revealed tumor infiltration to the SMA and/or hepatic artery (HA) in 4 patients. Finally, 32 patients with BRPHC have undergone the procedure between April 2009 and June 2015. Twenty-four of 32 patients (75.0%) had negative resection margins, and the median number of lymph nodes harvested was 34. Lymph nodes around the SMA tested positive for metastasis in 13 patients (40.6%), and those around the HA tested positive for metastasis in 7 patients (21.9%). Complications occurred in 14 patients (43.7%), with no perioperative mortality. Overall survival rates were 65.3% at 1 year and 35.2% at 3 years. CONCLUSIONS: Short-term results with the procedure may encourage surgical management for BRPHC.

Pulsed neutron time-dependent intensity modulation for quasi-elastic neutron scattering spectroscopy.

We propose a basic formula and demonstration for a high-resolution quasi-elastic neutron scattering (QENS) by combining the time-of-flight (TOF) method with Modulation of Intensity by Zero Effort (MIEZE) type neutron spin echo spectroscopy. The MIEZE technique has the potential to develop a unique approach to study on slow dynamics of condensed matter; however, the energy resolution is limited owing to the hypersensitivity of the MIEZE signal contrast to the echo condition, which is strongly affected by the alignment of the instruments and the sample. The narrow allowance of the optimal alignment is a major obstacle to the wide use of this technique. Combining the TOF method with MIEZE (TOF-MIEZE), the hypersensitivity of MIEZE signals is significantly alleviated with a short pulsed beam. This robustness is very useful to optimize experimental alignments and enables accurate measurements of QENS. The experimental results demonstrate the characteristic of the TOF-MIEZE technique and are well described by the formula presented in this study.

Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.

Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine. Acotiamide (0.3 and 1 µM) and itopride (1 and 3 µM) significantly enhanced the contraction of gastric body strips induced by electrical field stimulation (EFS), but mosapride (1 and 10 µM) did not. Acotiamide and itopride significantly enhanced the contraction of gastric body and antrum strips induced by acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also significantly enhanced the contraction of gastric body strips induced by ACh, but not that by CCh. In contrast, mosapride failed to enhance contractions induced by either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition of AChE, and the percentage inhibition of acotiamide (100 µM) against AChE activity was markedly reduced after the reaction mixture was dialyzed. In contrast, itopride exerted noncompetitive inhibition on AChE activity. These results indicate that acotiamide enhances ACh-dependent contraction in gastric strips of guinea pigs via the inhibition of AChE activity, and that it exerts mixed and reversible inhibition of AChE derived from guinea pig stomach.