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Introduction: Nocturia is a common symptom of lower urinary tract syndrome (LUTS). In previous studies, a close association between LUTS and colorectal inflammation has been reported. However, evidence regarding the association between nighttime urinary frequency and ulcerative colitis (UC) is limited. Herein, we investigated the association between nighttime urinary frequency and clinical outcomes of UC. Methods: We surveyed 287 Japanese patients with UC. A self‐administered questionnaire was used to collect the information on the variables studied. Patients were divided into three groups based on nighttime urinary frequency: (1) no voids, (2) one void, and (3) two or more voids. The assessment of clinical outcomes was based on mucosal healing (MH) and clinical remission (CR). The association between nighttime urinary frequency and prevalence of MH and CR was evaluated using multivariate logistic regression analyses. Results: The prevalence of one nighttime frequency and two or more nighttime frequency in this cohort was 35.5% and 26.8%, respectively. The percentage of MH and CR was 24.7% and 59.2%, respectively. Two or more nighttime frequency (adjusted odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.13–0.73) was independently and inversely associated with MH. In nonelderly patients (<70 years) and patients in CR, an association between two or more nighttime frequency and MH remained significant (non‐elderly: adjusted OR: 0.27, 95% CI: 0.09–0.72 and only CR: adjusted OR: 0.34, 95% CI: 0.12–0.90). Conclusion: Nighttime urinary frequency was independently and inversely associated with MH in Japanese patients with UC. Nighttime urinary frequency may serve as a complementary physical sign of MH in patients with UC. [ABSTRACT FROM AUTHOR]

Socioeconomic status is a risk factor for poor disease prognosis. No studies of patients with ulcerative colitis (UC) have investigated the association between socioeconomic status and erectile dysfunction (ED), although UC is independently positively associated with ED. Therefore, the purpose of this survey to evaluate this issue in Japanese patients with UC. The study enrolled 165 patients with UC. Education status (low, middle, high) and household income (low, middle, high) were classified in three groups using self-administered surveys. The information regarding the Sexual Health Inventory for Men (SHIM) was obtained using self-administered questionnaires. The definition of mild to moderate or severe ED and severe ED was SHIM score <17 and SHIM score <8, respectively. The prevalence of mild to moderate or severe ED and severe ED was 64.9% and 47.9%, respectively. In crude analysis, household income was inversely associated with mild to moderate or severe ED and severe ED. After adjustment for age, current drinking, current smoking, exercise habit, body mass index, mucosal healing, and duration of UC, high household income was independently and inversely associated with mild to moderate or severe ED (adjusted odds ratio [OR] 0.23, 95% confidence interval [CI] [0.05, 0.93], p for trend =.038) and severe ED (adjusted OR 0.26, 95% CI [0.07, 0.85], p for trend =.024). In contrast, no association between education status and ED was found. In conclusion, household income was independently and inversely associated with ED in Japanese UC patients. [ABSTRACT FROM AUTHOR]

Objective: Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC. Methods: One hundred and thirty‐six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self‐administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self‐administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C‐reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression. Results: The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03–7.48, p for trend =0.044). No association between other marker and ED was found. Conclusion: Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients. [ABSTRACT FROM AUTHOR]

Aim: Age is a risk factor for constipation. Constipation is common in patients with ulcerative colitis (UC) and has been positively associated with disease activity, but evidence is limited. This study aimed to assess the association between disease activity and constipation in patients with UC. Methods : The study subjects consisted of 290 Japanese UC patients. The definition of constipation was based on Rome I criteria and/or medication for constipation. Information on and lifestyle habits was obtained from a self-administered questionnaire. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0. Clinical remission (CR) was defined as both the absence of rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The prevalence of constipation is not associated with MH, CR, duration of UC and disease extent of UC. The prevalence of constipation among age groups, <40, 40–49 years, 50–59 years, 60–69 years, and >70 years was 10.0%, 5.8%, 15.7%, 11.8%, and 25.6%, respectively. >70 years was independently and positively associated with the prevalence of constipation (adjusted odds ratio 3.64 [95% confidence interval 1.26, 10.95], p for trend:.001). Conclusions: Aging was independently and positively associated with the prevalence of constipation in UC. [ABSTRACT FROM AUTHOR]

Introduction: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC. Methods: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0–1, respectively. Results: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04–6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22–11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia. Conclusions: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C. [ABSTRACT FROM AUTHOR]

Summary: Restless legs syndrome (RLS) is a common sleep disorder in the Western population. The prevalence of restless legs syndrome in the Japanese population is 4.6%. Inflammatory and/or immune alteration might be associated with the development of restless legs syndrome. Ulcerative colitis is a chronic inflammatory bowel disease. Evidence regarding the association between ulcerative colitis and the prevalence of restless legs syndrome is limited. Herein, we investigated the association between clinical outcomes and the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis. This was a cross‐sectional study using baseline data from a prospective cohort study. Subjects in this study were 273 patients with ulcerative colitis. The definition of restless legs syndrome was achieved using a self‐administered questionnaire based on the diagnostic criteria for restless legs syndrome in an epidemiological study approved by the Executive Committee of the International Restless Leg Syndrome Study Group in 2002. Clinical outcomes were clinical remission and mucosal healing. The association between clinical remission and mucosal healing and the prevalence of restless legs syndrome was assessed by multivariate logistic regression analyses. The percentage of clinical remission and mucosal healing was 58.4% and 63.1%, respectively. The prevalence of restless legs syndrome in this cohort was 4.7%. Clinical remission (adjusted odds ratio 0.23, 95% confidence interval 0.05–0.93) and mucosal healing (adjusted odds ratio 0.23, 95% confidence interval 0.05–0.90) were independently inversely associated with restless legs syndrome. No association between serum haemoglobin and restless legs syndrome was found. In conclusion, clinical remission and mucosal healing were independently and inversely associated with the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

We examined whether antigen-specific immune responses are lower in mice with protein energy malnutrition (PEM mice) compared with nourished (control) mice. The mechanisms underlying reduced antigen-specific immune responses of PEM mice were evaluated through analysis of the functional capacities of antigen-presenting dendritic cells (DC). PEM mice were produced by subjecting male C57BL/6 mice for 52 wk to a daily food intake equivalent to 70% of the mean amount consumed by the control mice that consumed food ad libitum. PEM mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (H BsAg) at 52 wk and hu moral and cellular immune responses to H BsAg were evaluated at 58 wk. Lymphoproliferative assays were performed to assess the functional capacities of lymphocytes and DC. After 52 wk of food restriction, PEM mice had a 49% lower body weight than controls, almost no subcutaneous fat, severe muscle wasting, and atrophied spleen. All control mice developed antibodies to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen as a result of immunization with the hepatitis B vaccine. PEM mice, however, were almost unresponsive to immunization with the hepatitis B vaccine. In PEM mice, the numbers of spleen DC, the T lymphocyte stimulatory capacities of DC, and their production of IL-12p70 and I FN-[gamma], was less than those of control mice (P < 0.05). We suggest that chronic undernutrition disrupts antigen- specific immune responses and that this disruption can be attributed at least in part to reduced frequencies and impaired functions of DC.

Background: Atrophic gastritis can be classified according to characteristic mucosal patterns observed by Blue LASER Imaging (BLI) in a medium-range to distant view. Aims: To facilitate the endoscopic diagnosis of Helicobacter pylori (HP)-related gastritis, we investigated whether atrophic mucosal patterns correlated with HP infection based on the image interpretations of three endoscopists blinded to clinical features. Methods: This study included 441 patients diagnosed as having atrophic gastritis by upper gastrointestinal endoscopy at Nishikawa Gastrointestinal Clinic between April 1, 2015 and March 31, 2016. The presence/absence of HP infection was not taken into consideration. Endoscopy was performed using a Fujifilm EG-L580NW scope. Atrophic mucosal patterns observed by BLI were classified into Spotty, Cracked and Mottled. Image interpretation results were that 89, 122 and 228 patients had the Spotty, Cracked and Mottled patterns, respectively, and 2 patients an undetermined pattern. Further analyses were performed on 439 patients, excluding the 2 with undetermined patterns. Results: The numbers of patients testing negative/positive for HP infection in the Spotty, Cracked and Mottled pattern groups were 12/77, 105/17, and 138/90, respectively. The specificity, positive predictive value and positive likelihood ratio for endoscopic diagnosis with positive HP infection based on the Spotty pattern were 95.3%, 86.5% and 8.9, respectively. In all patients with the Spotty pattern before HP eradication, the Cracked pattern was observed on subsequent post-eradication endoscopy. Conclusions: The Spotty pattern may represent the presence of HP infection, the Cracked pattern, a post-inflammatory change as seen after HP eradication, and the Mottled pattern, intestinal metaplasia. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), which is characterized by a dysregulated intestinal immune response, is postulated to be con-trolled by intestinal self-antigens and bacterial Ags. Fecal extracts called cecal bacterial Ag (CBA) have been implicated in the pathogenesis of IBD. In this study, we identified a major protein of CBA related to the pathogenesis of IBD and established a ther-apeutic approach using Ag-pulsed regulatory dendritic cells (Reg-DCs). Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, carbonic anhydrase I (CA I) was identified as a major protein of CBA. Next, we induced colitis by transfer of CD4+CD25- T cells obtained from BALB/c mice into SCID mice. Mice were treated with CBA- or CA I-pulsed Reg-DCs (Reg-DCSCBA or Reg-DCsCA1), which expressed CD200 receptor 3 and produced high levels of IL-10. Treatment with Reg-DCsCBA and Reg-DCsCA1 ameliorated colitis. This effect was shown to be Ag-specific based on no clinical response of irrelevant Ag (keyhole limpet hemocyanin)-pulsed Reg-DCs. Foxp3 mRNA expression was higher but RORγt mRNA expression was lower in the mesenteric lymph nodes (MLNs) of the Reg-DCsCA1-treated mice compared with those in the MLNs of control mice. In the MLNs, Reg-DCsCA1-treated mice had higher mRNA expression of IL-10 and TGF-&bgr;1 and lower IL-17 mRNA expression and protein production compared with those of control mice. In addition, Reg-DCsCBA-treated mice had higher Foxp3+CD4+CD25+ and IL-10-producing regulatory T cell frequencies in MLNs. In conclusion, Reg-DCsCAi protected progression of colitis induced by CD4+CD25- T cell transfer in an Ag-specific manner by inducing the differentiation of regulatory T cells. [ABSTRACT FROM AUTHOR]

Hepatitis B surface antigen (HBsAg)-pulsed murine spleen dendritic cells (DCs) have shown tremendous therapeutic potentials in chronic hepatitis B virus (HBV) carriers however, there has been no study regarding the feasibility of using HBsAg-pulsed DCs in human. Five human healthy volunteers with no apparent concomitant diseases were enrolled in this study. DCs were enriched from peripheral blood of each volunteer in endotoxin-free and sterilized conditions. HBsAg-pulsed DCs were prepared by culturing DCs with a commercial-available human grade vaccine containing HBsAg. After assessing the expression of HLA DR and CD86 on HBsAg-pulsed DCs, 5 million HBsAg-pulsed DCs were injected intradermally, once, to each volunteer. The volunteers were serially observed for safety and efficacy of administration of HBsAg-pulsed DCs. No evidence of physical, biochemical, and immunological abnormalities were documented in any volunteer during the next 28 days following administration of HBsAg-pulsed DCs. A single administration of HBsAg-pulsed DCs resulted in upregulation of anti-HBs in two anti-HBs+ volunteers. Moreover, anti-HBs were detected in two anti-HBs- volunteer, 2 weeks after administration of HBsAg-pulsed DCs. This study provides the scientific and ethical basis for using HBsAg-pulsed DCs for therapeutic and prophylactic purposes in patients with chronic hepatitis B and non-responders to hepatitis B vaccine, respectively. [Copyright &y& Elsevier]

Background & Aims: The commensal microbiota is believed to have an important role in regulating immune responsiveness and preventing intestinal inflammation. Intestinal microbes produce signals that regulate inflammation via Toll-like receptor (TLR) signaling, but the mechanisms of this process are poorly understood. We investigated the role of the anti-inflammatory cytokine interleukin (IL)-10 in this signaling pathway using a mouse model of colitis. Methods: Clinical, histopathologic, and functional parameters of intestinal inflammation were evaluated in TLR4−/−, IL-10−/−, and TLR4−/− × IL-10−/− mice that were free of specific pathogens and in TLR4−/− × IL-10−/− mice following eradication and reintroduction of Helicobacter hepaticus. Regulatory T-cell (Treg) function was evaluated by crossing each of the lines with transgenic mice that express green fluorescent protein under control of the endogenous regulatory elements of Foxp3. Apoptotic cells in the colonic lamina propria were detected by a TUNEL assay. Results: TLR4-mediated signals have 2 interrelated roles in promoting inflammation in TLR4−/− × IL-10−/− mice. In the absence of TLR4-mediated signals, secretion of proinflammatory and immunoregulatory cytokines is dysregulated. Tregs (Foxp3+) that secrete interferon-γ and IL-17 accumulate in the colonic lamina propria of TLR4−/− × IL-10−/− mice and do not prevent inflammation. Aberrant control of epithelial cell turnover results in the persistence of antigen-presenting cells that contain apoptotic epithelial fragments in the colonic lamina propria of Helicobacter-infected TLR4−/− mice. Conclusions: In mice that lack both IL-10- and TLR4-mediated signals, aberrant regulatory T-cell function and dysregulated control of epithelial homeostasis combine to exacerbate intestinal inflammation. [Copyright &y& Elsevier]