Ulcerative colitis (UC) is an inflammatory condition of the intestine, resulting from an increase in oxidative stress and pro-inflammatory mediators. In this study, the extract of endophytic bacterium Rhizobium aegyptiacum was prepared for the first time using liquid chromatography-mass spectrometry (LC-MS). In addition, also for the first time, the protective potential of R. aegyptiacum was revealed using an in vivo rat model of UC. The animals were grouped into four categories: normal control (group I), R. aegyptiacum (group II), acetic acid (AA)‍-induced UC (group III), and R. aegyptiacum-treated AA-induced UC (group IV). In group IV, R. aegyptiacum was administered at 0.2 mg/kg daily for one week before and two weeks after the induction of UC. After sacrificing the rats on the last day of the experiment, colon tissues were collected and subjected to histological, immunohistochemical, and biochemical investigations. There was a remarkable improvement in the histological findings of the colon tissues in group IV, as revealed by hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and periodic acid-Schiff (PAS) staining. Normal mucosal surfaces covered with a straight, intact, and thin brush border were revealed. Goblet cells appeared magenta in color, and there was a significant decrease in the distribution of collagen fibers in the mucosa and submucosal connective tissues. All these findings were comparable to the respective characteristics of the control group. Regarding cyclooxygenase-2 (COX-2) immunostaining, a weak immune reaction was shown in most cells. Moreover, the colon tissues were examined using a scanning electron microscope, which confirmed the results of histological assessment. A regular polygonal unit pattern was seen with crypt orifices of different sizes and numerous goblet cells. Furthermore, the levels of catalase (CAT), myeloperoxidase (MPO), nitric oxide (NO), interleukin-6 (IL-6), and interlukin-1β (IL-1β) were determined in the colonic tissues of the different groups using colorimetric assay and enzyme-linked immunosorbent assay (ELISA). In comparison with group III, group IV exhibited a significant rise (P<0.05) in the CAT level but a substantial decline (P<0.05) in the NO, MPO, and inflammatory cytokine (IL-6 and IL-1β) levels. Based on reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the tumor necrosis factor-‍α (TNF-‍α) gene expression was upregulated in group III, which was significantly downregulated (P<0.05) by treatment with R. aegyptiacum in group IV. On the contrary, the heme oxygenase-1 (HO-1) gene was substantially upregulated in group IV. Our findings imply that the oral consumption of R. aegyptiacum ameliorates AA-induced UC in rats by restoring and reestablishing the mucosal integrity, in addition to its anti-oxidant and anti-inflammatory effects. Accordingly, R. aegyptiacum is potentially effective and beneficial in human UC therapy, which needs to be further investigated in future work.
Animals ; Colitis, Ulcerative/prevention & control* ; Rats ; Male ; Rhizobium ; Disease Models, Animal ; Colon/pathology* ; Rats, Sprague-Dawley ; Oxidative Stress ; Cyclooxygenase 2/metabolism*

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-‍‍(4,5-dimethylthiazol-2-yl)-2,‍5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.
Animals ; Antioxidants/pharmacology* ; Colitis/prevention & control* ; Colitis, Ulcerative/metabolism* ; Colon/metabolism* ; Dextran Sulfate/toxicity* ; Disease Models, Animal ; Gastrointestinal Microbiome ; Inflammation/metabolism* ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Spirulina

OBJECTIVETo evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).

DATA SOURCESWe completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: "inflammatory bowel disease (IBD)" OR "Crohn's disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators."

STUDY SELECTIONThe inclusion criteria of articles were that the studies: (1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents). The exclusion criteria of articles were that the studies: (1) History of hepatitis B virus (HBV), influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.

RESULTSPatients treated with immunomodulators were associated with lower response rates to vaccination.

CONCLUSIONSImmunomodulators may impair the immune response to vaccination in patients with IBD. Vaccination should be made at the time of diagnosis or before starting immunosuppressed therapy.

Colitis, Ulcerative ; prevention & control ; Crohn Disease ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Inflammatory Bowel Diseases ; prevention & control ; Vaccination

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.
Alkaloids ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrestins ; metabolism ; Colitis, Ulcerative ; metabolism ; pathology ; prevention & control ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Quinolizines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, delta ; metabolism ; Signal Transduction ; drug effects ; beta-Arrestins

BACKGROUND/AIMS: Vaccinations are generally recommended in patients with inflammatory bowel disease (IBD). However, several studies showed low rates of vaccinations in IBD patients. Furthermore, vaccination rate among IBD patients in Korea has never been investigated. We investigated the vaccination rate among IBD patients in Korea and evaluated some factors that might affect the vaccination rate. METHODS: From November 2011 to February 2012, a total of 192 patients with IBD who visited Samsung Medical Center (Seoul, Korea) answered the IRB-approved questionnaire. The questionnaire included their sex, age, residence, past medical history, type of IBD, duration of illness, medications, history of vaccination about measles-mumps-rubella (MMR), varicella, tetanus-diphtheria (Td), influenza, hepatitis A and B, pneumococcus and human papilloma virus (HPV). RESULTS: One hundred twenty one (63.0%) male and 71 (37.0%) female answered the questionnaire. The mean age of the enrolled patients was 39.7 (18-76) years. Eighty four patients (43.8%) had ulcerative colitis and 108 patients (56.3%) had Crohn's disease (CD). The percentage of the patients who had got vaccination was 42.2% for MMR, 34.9% for varicella, 15.6% for Td, 37.5% for influenza, 15.6% for hepatitis A, 52.6% for hepatitis B, 6.3% for pneumococcus and 11.3% for HPV respectively. Not knowing the necessity or the existence were the common reasons for non-vaccination. Age less than 40 years, CD patients and duration of illness less than 10 years were associated with a higher vaccination rate (p=0.002, 0.015 and 0.020, respectively). CONCLUSIONS: Immunization rates for recommended vaccinations were very low in patients with IBD. Efforts to improve vaccination rate are needed.
Adolescent ; Adult ; Aged ; Chickenpox/prevention & control ; Colitis, Ulcerative/pathology ; Crohn Disease/pathology ; Diphtheria/prevention & control ; Female ; Hepatitis A/prevention & control ; Hepatitis B/prevention & control ; Humans ; Inflammatory Bowel Diseases/*immunology/pathology ; Male ; Measles/prevention & control ; Middle Aged ; Mumps/prevention & control ; Papillomavirus Infections/prevention & control ; Pneumococcal Infections/prevention & control ; Questionnaires ; Republic of Korea ; Rubella/prevention & control ; Tetanus/prevention & control ; *Vaccination ; Young Adult

Colitis, Ulcerative ; prevention & control ; therapy ; Humans ; Integrative Medicine ; Remission Induction

BACKGROUND/AIMS: Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study. METHODS: Prevalence of smoking at the time of IBD diagnosis were compared between CD and UC patients in Kyung-Hee Medical Center with healthy general population at age-, gender-, and time period-adjusted rates. We investigated the smoking status of IBD patients at the time of diagnosis by telephone interview. There were 178 IBD patients (98 UC patients and 80 CD patients) between January 1995 and December 2004. RESULTS: The male to female ratio in CD and UC were 2:1 and 1:1.4, respectively. The onset of age was 28.2 years and 38.8 years, respectively. The prevalence of smoking was significantly lower in CD and UC patients than in the general population (CD; odds ratio 0.21, 95% confidence interval 0.12-0.41, p<0.001, UC; odds ratio 0.06, 95% confidence interval 0.03-0.14, p<0.001). After statistical adjustment for gender and age at the diagnosis of IBD, the odds ratio of a current smoker diagnosed as UC was 73% lower than that of CD (adjusted odds ratio 0.27, 95% confidence interval 0.12-0.59, p<0.001). In contrast, being a former smoker showed a risk of approximate 1.27-fold higher likelihood of having UC diagnosis (adjusted odds ratio 1.27, confidence interval 0.41-3.95, p=0.68). CONCLUSIONS: Cigarette smoking is protective against developing UC at any age, but is not associated with the development of CD in Korean population. Former smoking is not the high risk factor in developing UC.
Adult ; Colitis, Ulcerative/*prevention & control ; Crohn Disease/*etiology ; Female ; Humans ; Male ; Risk Factors ; *Smoking/adverse effects