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

OBJECTIVEUlcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. In the present study, the effect of ginger (rhizome of Zingiber officinale Roscoe) volatile oil on a rat model of colitis was evaluated.

METHODSVolatile oil of ginger with doses of 100, 200, and 400 mg/kg, prednisolone (4 mg/kg), or vehicle were administered orally to groups of male Wistar rats (n = 6) for 5 d. Animals were randomly divided into 6 groups, each group consisting of 6 rats. Colitis was induced by intracolonic instillation of 2 mL of 4% (v/v) acetic acid solution. All rats were sacrificed 24 h later and the tissue injuries were assessed macroscopically and histopathologically.

RESULTSGinger volatile oil with all doses reduced colon weight/length ratio (P < 0.01) and the effects were similar to the reference drugs. Higher oral doses of volatile oil (200 and 400 mg/kg) reduced ulcer severity (P < 0.05 and P < 0.01), ulcer area (P < 0.01) and ulcer index (P < 0.01). On the other hand, evaluation of microscopic scores showed that the dose of 400 mg/kg of volatile oil was effective to reduce inflammation severity (P < 0.01) and inflammation extent (P < 0.05) compared to the control group.

CONCLUSIONIt is concluded that ginger volatile oil could effectively reduce symptoms of experimental colitis in a dose-dependent manner.

Acetic Acid ; pharmacology ; Animals ; Colitis ; chemically induced ; pathology ; prevention & control ; Dose-Response Relationship, Drug ; Ginger ; chemistry ; Male ; Microscopy ; Oils, Volatile ; isolation & purification ; therapeutic use ; Plant Extracts ; isolation & purification ; therapeutic use ; Plant Oils ; isolation & purification ; therapeutic use ; Rats ; Rats, Wistar ; Rhizome ; chemistry

BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes makes it a therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low dose B-98 (DSS+B-98 20 mg/kg) and high dose B-98 (DSS+B-98 100 mg/kg). B-98 was administered with 3% DSS intraperitoneally. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of inflammatory cytokines interleukin (IL)-6 was determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2 cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS: The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading compared with the DSS colitis group (p<0.01). The expression of IL-6 in colonic tissue was significantly lower in the B-98 groups than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1, Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98 group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17 involved cellular immunity.
Acute Disease ; Animals ; Arachidonate 5-Lipoxygenase/chemistry/metabolism ; Benzoxazoles/chemistry/*pharmacology ; Colitis/chemically induced/pathology/*prevention & control ; Colon/drug effects/pathology/physiology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Forkhead Transcription Factors/metabolism ; Injections, Intraperitoneal ; Interleukin-6/genetics/metabolism ; Lipoxygenase Inhibitors/chemistry/*pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Severity of Illness Index ; T-Lymphocytes/classification/*drug effects/metabolism

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

Clostridium difficile colitis (CDC) has been associated with virtually all available antibiotics. It is well known that administration of drugs by the ocular route can result in systemic absorption with the possibility of systemic effect. We report a case of a 74-year-old woman who was treated with 0.5% levofloxacin eyedrops for ten weeks running for the post operative management of two separate bilateral cataract surgeries. Toxin assay for C. difficile was positive and the endoscopic findings were compatible with CDC. The plasma concentrations reached after intraocular administration of levofloxacin seem so trivial, but the administration of topical agents could make accumulated effect and be a potential cause of systemic toxicity.
Absorption ; Aged ; Anti-Bacterial Agents ; Cataract ; Centers for Disease Control and Prevention (U.S.) ; Clostridium difficile* ; Clostridium* ; Colitis* ; Enterocolitis ; Female ; Humans ; Levofloxacin* ; Ophthalmic Solutions ; Plasma ; Running

Clostridium difficile colitis (CDC) has been associated with virtually all available antibiotics. It is well known that administration of drugs by the ocular route can result in systemic absorption with the possibility of systemic effect. We report a case of a 74-year-old woman who was treated with 0.5% levofloxacin eyedrops for ten weeks running for the post operative management of two separate bilateral cataract surgeries. Toxin assay for C. difficile was positive and the endoscopic findings were compatible with CDC. The plasma concentrations reached after intraocular administration of levofloxacin seem so trivial, but the administration of topical agents could make accumulated effect and be a potential cause of systemic toxicity.
Absorption ; Aged ; Anti-Bacterial Agents ; Cataract ; Centers for Disease Control and Prevention (U.S.) ; Clostridium difficile* ; Clostridium* ; Colitis* ; Enterocolitis ; Female ; Humans ; Levofloxacin* ; Ophthalmic Solutions ; Plasma ; Running

PURPOSE: Clostridium difficile colitis (CDC) is a nosocomial infection. We attempted to discover the risk factors for the development of CDC in patients admitted to our surgical ward. METHODS: We conducted a retrospective chart review of all patients admitted to our surgical ward between January 2010 and July 2011. CDC was confirmed when toxin A/B or toxin B polymerase chain reaction was detected in the stool and clinical symptoms, such as diarrhea, were present. We divided patients into the CDC and non-CDC groups, and compared the clinical features between the two groups. RESULTS: The rate of CDC occurrence was 0.4% (19/4,720 patients). Univariate analysis showed that colectomy (P < 0.001), hospital stays longer than 10 days (P < 0.001), aged over 55 years (P < 0.001) and transfer from medical ward (P = 0.009) were significant parameters for CDC. Multivariate analysis showed that colectomy (P < 0.001; odds ratio [OR], 8.405; 95% confidence interval [CI], 2.927 to 24.132) and hospital stays longer than 10 days (P = 0.035; OR, 10.253; 95% CI, 1.176 to 89.392) were high risk factors for CDC occurrence in the surgical ward. CONCLUSION: The risk factors for CDC in a surgical ward could be colectomy and a long duration of hospitalization. Therefore, clinicians should consider the possibility of CDC when patients undergo colectomy, are admitted for a long time, and have postoperative diarrhea.
Aged ; Centers for Disease Control and Prevention (U.S.) ; Clostridium ; Clostridium difficile ; Colectomy ; Colitis ; Cross Infection ; Diarrhea ; Hospitalization ; Humans ; Length of Stay ; Multivariate Analysis ; Odds Ratio ; Polymerase Chain Reaction ; Retrospective Studies ; Risk Factors

OBJECTIVETo study the effect of NOD2 on colitis pathogenesis in experimental rats, and discuss therapeutical effect and mechanism of kushenin injection (OMT) on colitis in experimental rats.

METHODFourty Sprague-Dawley (SD) rats were randomly divided into four groups: the normal control group, the model group, the SASP group, and the OMT group, with 10 rats in each group. Except the normal control group, models were established in the remaining three groups with TNBS. The OMT group was injected with kushenin injection, the SASP group was orally administered with mesalazine suspension, the model group and the normal group were orally administered with distilled water for 15 days. Colon lesion score and histological score of experimental rats were observed. Expression of NOD2, NF-kappaB p65 protein in rats colonic mucous was detected by immunohistochemistry. Expression of IL-6 in rat colon mucous was detected by ELISA.

RESULTCompared with normal control group, the expression of NOD2, NF-kappaB p65 and IL-6 in colonic mucosa of the model group were significantly increased (P < 0.01). The SASP group and the OMT group showed lower expressions of NOD2, NF-kappaB p65 and IL-6 in colonic mucosa than the model group (P < 0.01, P < 0.05).

CONCLUSIONThe over expression of colonic mucosa proteins NOD2 and NF-kappaB p65 and increasing secretion of IL-6 take part in the appearance and development of ulcerative colitis. OMT can attenuate ulcerative colitis and protect colonic mucosa by inhibiting expression of NOD2, NF-kappaB p65 and decreasing IL-6.

Animals ; Colitis ; metabolism ; pathology ; physiopathology ; prevention & control ; Colon ; drug effects ; metabolism ; pathology ; physiopathology ; Eating ; drug effects ; Gene Expression Regulation ; drug effects ; Injections ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; physiopathology ; Male ; Nod2 Signaling Adaptor Protein ; metabolism ; Organ Size ; drug effects ; Pterocarpans ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism