Colitis: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.Colitis, Ulcerative: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.Colitis, Ischemic: Inflammation of the COLON due to colonic ISCHEMIA resulting from alterations in systemic circulation or local vasculature.Colitis, Microscopic: A condition characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. This syndrome was first described in 1980 by Read and associates. Subtypes include COLLAGENOUS COLITIS and LYMPHOCYTIC COLITIS. Both have similar clinical symptoms and are distinguishable only by histology.Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4-POSITIVE T-LYMPHOCYTES. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications.Colitis, Collagenous: A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show larger-than-normal band of subepithelial COLLAGEN.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups.Colitis, Lymphocytic: A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show infiltration of LYMPHOCYTES in the superficial EPITHELIUM and the underlying connective tissue (lamina propria).Crohn Disease: A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Inflammatory Bowel Diseases: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)Rectum: The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL.Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 220.127.116.11.Gastrointestinal Agents: Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion.Colectomy: Excision of a portion of the colon or of the whole colon. (Dorland, 28th ed)Proctocolectomy, Restorative: A surgical procedure involving the excision of the COLON and RECTUM and the formation of an ILEOANAL RESERVOIR (pouch). In patients with intestinal diseases, such as ulcerative colitis, this procedure avoids the need for an OSTOMY by allowing for transanal defecation.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon.Dysentery, Amebic: DYSENTERY caused by intestinal amebic infection, chiefly with ENTAMOEBA HISTOLYTICA. This condition may be associated with amebic infection of the LIVER and other distant sites.Ileostomy: Surgical creation of an external opening into the ILEUM for fecal diversion or drainage. This replacement for the RECTUM is usually created in patients with severe INFLAMMATORY BOWEL DISEASES. Loop (continent) or tube (incontinent) procedures are most often employed.Administration, Rectal: The insertion of drugs into the rectum, usually for confused or incompetent patients, like children, infants, and the very old or comatose.Enterocolitis, Pseudomembranous: An acute inflammation of the INTESTINAL MUCOSA that is characterized by the presence of pseudomembranes or plaques in the SMALL INTESTINE (pseudomembranous enteritis) and the LARGE INTESTINE (pseudomembranous colitis). It is commonly associated with antibiotic therapy and CLOSTRIDIUM DIFFICILE colonization.Pouchitis: Acute INFLAMMATION in the INTESTINAL MUCOSA of the continent ileal reservoir (or pouch) in patients who have undergone ILEOSTOMY and restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).Mice, Inbred C57BLEnterocolitis: Inflammation of the MUCOSA of both the SMALL INTESTINE and the LARGE INTESTINE. Etiology includes ISCHEMIA, infections, allergic, and immune responses.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Diarrhea: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.Colonic Pouches: Sacs or reservoirs created to function in place of the COLON and/or RECTUM in patients who have undergone restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).Acetic Acid: Product of the oxidation of ethanol and of the destructive distillation of wood. It is used locally, occasionally internally, as a counterirritant and also as a reagent. (Stedman, 26th ed)Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Probiotics: Live microbial DIETARY SUPPLEMENTS which beneficially affect the host animal by improving its intestinal microbial balance. Antibiotics and other related compounds are not included in this definition. In humans, lactobacilli are commonly used as probiotics, either as single species or in mixed culture with other bacteria. Other genera that have been used are bifidobacteria and streptococci. (J. Nutr. 1995;125:1401-12)Interleukin-10: A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Cecum: The blind sac or outpouching area of the LARGE INTESTINE that is below the entrance of the SMALL INTESTINE. It has a worm-like extension, the vermiform APPENDIX.Citrobacter rodentium: A species of gram-negative bacteria in the genus CITROBACTER, family ENTEROBACTERIACEAE. As an important pathogen of laboratory mice, it serves as a model for investigating epithelial hyperproliferation and tumor promotion. It was previously considered a strain of CITROBACTER FREUNDII.Ileitis: Inflammation of any segment of the ILEUM and the ILEOCECAL VALVE.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Helicobacter hepaticus: A species of HELICOBACTER that colonizes the CECUM and COLON of several strains of MICE, and is associated with HEPATITIS and carcinogenesis.Mice, Inbred BALB CAnti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Megacolon, Toxic: An acute form of MEGACOLON, severe pathological dilatation of the COLON. It is associated with clinical conditions such as ULCERATIVE COLITIS; CROHN DISEASE; AMEBIC DYSENTERY; or CLOSTRIDIUM ENTEROCOLITIS.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Oxazolone: Immunologic adjuvant and sensitizing agent.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Clostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Colon, Sigmoid: A segment of the COLON between the RECTUM and the descending colon.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure.Colonic Diseases: Pathological processes in the COLON region of the large intestine (INTESTINE, LARGE).Proctitis: INFLAMMATION of the MUCOUS MEMBRANE of the RECTUM, the distal end of the large intestine (INTESTINE, LARGE).Intestine, Large: A segment of the LOWER GASTROINTESTINAL TRACT that includes the CECUM; the COLON; and the RECTUM.Cholangitis, Sclerosing: Chronic inflammatory disease of the BILIARY TRACT. It is characterized by fibrosis and hardening of the intrahepatic and extrahepatic biliary ductal systems leading to bile duct strictures, CHOLESTASIS, and eventual BILIARY CIRRHOSIS.Mucous Membrane: An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa.Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)Colonic Neoplasms: Tumors or cancer of the COLON.Proctocolitis: Inflammation of the RECTUM and the distal portion of the COLON.Acute Disease: Disease having a short and relatively severe course.Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Dinitrofluorobenzene: Irritants and reagents for labeling terminal amino acid groups.Gastrointestinal Hemorrhage: Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.Bacterial Translocation: The passage of viable bacteria from the GASTROINTESTINAL TRACT to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the INTESTINAL MUCOSA resulting in increased intestinal permeability. Bacterial translocation from the lung to the circulation is also possible and sometimes accompanies MECHANICAL VENTILATION.Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the ABDOMINAL WALL and conveys their blood vessels and nerves.Clostridium Infections: Infections with bacteria of the genus CLOSTRIDIUM.Collagen Diseases: Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Ulcer: A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.Mucin-2: A gel-forming mucin found predominantly in SMALL INTESTINE and variety of mucous membrane-containing organs. It provides a protective, lubricating barrier against particles and infectious agents.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.
Colitis: - K52Microscopic colitisLymphocytic colitis: Lymphocytic colitis, a subtype of microscopic colitis, is a rare condition characterized by chronic non-bloody watery diarrhea. The colonoscopy is normal but the mucosal biopsy reveals an accumulation of lymphocytes in the colonic epithelium and connective tissue (lamina propria).Crohn's Disease Activity Index: The Crohn's Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. This is of useful importance in research studies done on medications used to treat Crohn's disease; most major studies on newer medications use the CDAI in order to define response or remission of disease.Transverse folds of rectum: The transverse folds of rectum (or Houston's valves) are semi-lunar transverse folds of the rectal wall that protrude into the rectum, not the anal canal as that lies below the rectum. Their use seems to be to support the weight of fecal matter, and prevent its urging toward the anus, which would produce a strong urge to defecate.SulfasalazineMyeloperoxidase deficiency: Myeloperoxidase deficiency is an autosomal recessive genetic disorder featuring deficiency, either in quantity or of function, of myeloperoxidase, an enzyme found in certain phagocytic immune cells, especially polymorphonuclear leukocytes.FontolizumabColectomyProctocolectomy: Proctocolectomy is the surgical removal of the rectum and all or part of the colon. It is a most widely accepted surgical method for ulcerative colitis and Familial adenomatous polyposis (FAP) .Gross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.Virtual colonoscopy: Virtual colonoscopy (VC, also called CT Colonography or CT Pneumocolon) is a medical imaging procedure which uses x-rays and computers to produce two- and three-dimensional images of the colon (large intestine) from the lowest part, the rectum, all the way to the lower end of the small intestine and display them on a screen. The procedure is used to diagnose colon and bowel disease, including polyps, diverticulosis and cancer.IleostomyIferanserin: Iferanserin (INN; VEN-309) is a drug which acts as a selective 5-HT2A receptor antagonist. It is under development as an intra-rectal formulation for the treatment of hemorrhoid disease, and as of February 2012, is in phase IIb clinical trials.Colitis-X: Colitis X, equine colitis X or peracute toxemic colitis is a catchall term for various fatal forms of acute or peracute colitis found in horses, but particularly a fulminant colitis where clinical signs include sudden onset of severe diarrhea, abdominal pain, shock, and dehydration. Death is common, with 90% to 100% mortality, usually in less than 24 hours.Food protein-induced enterocolitis syndrome: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a severe systemic response to food protein that typically occurs 1 to 4 hours after the ingestion of the causative food and frequently develops in the first few years of life.Powell GK.Congenital chloride diarrhea: Congenital chloride diarrhea (CCD, also congenital chloridorrhea or Darrow Gamble syndrome) is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells.Acetic acid bacteria: Acetic acid bacteria (AAB) derive their energy from the oxidation of ethanol to acetic acid during fermentation. They are gram-negative, aerobic, rod-shaped bacteria.Mutaflor: Mutaflor is a probiotic consisting of a viable non-pathogenic bacteria strain named Escherichia coli Nissle 1917.Mutaflor Information page "The Escherichia coli strain Nissle 1917-designated DSM 6601 in the German Collection for Microorganisms in Braunschweig is one of the best-examined and therapeutically relevant bacterial strains worldwide" as claimed by the manufacturerManufacturers WebsiteProinflammatory cytokine: A proinflammatory cytokine is a cytokine which promotes systemic inflammation.CecectomyIntimin: Intimin is a virulence factor (adhesin) of EPEC (e.g.IleitisFetor hepaticusCelecoxibToxic megacolonC3H3NO2Brain biopsyFidaxomicinInflammation: Inflammation (Latin, [is part of the complex biological response of body tissues to harmful stimuli, such as pathogen]s, damaged cells, or irritants.Sigmoidocele: Sigmoidocele (also known as Pouch of Douglas descent) refers to a condition where the sigmoid colon descends (prolapses) into the lower pelvic cavity. This can obstruct the rectum and cause symptoms of obstructed defecation.Non-communicable disease: Non-communicable disease (NCD) is a medical condition or disease that is non-infectious or non-transmissible. NCDs can refer to chronic diseases which last for long periods of time and progress slowly.ProctitisHaustrum (anatomy): The haustra (singular haustrum) of the colon are the small pouches caused by sacculation (sac formation), which give the colon its segmented appearance. The teniae coli run the length of the large intestine.Secondary sclerosing cholangitis: Secondary sclerosing cholangitis abbreviated as (SSC) is a disease that is morphologically similar to primary sclerosing cholangitis (PSC) but that originates from a known pathological process. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced.AzathioprineOncotype DX Colon Cancer AssayPrednisoloneG-CSF factor stem-loop destabilising elementFluorobenzeneGlasgow-Blatchford score: The Glasgow-Blatchford bleeding score (GBS) is a screening tool to assess the likelihood that a patient with an acute upper gastrointestinal bleeding (UGIB) will need to have medical intervention such as a blood transfusion or endoscopic intervention. The tool may be able to identify patients who do not need to be admitted to hospital after a UGIB.Otospondylomegaepiphyseal dysplasia: Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive disorder of bone growth that results in skeletal abnormalities, severe hearing loss, and distinctive facial features. The name of the condition indicates that it affects hearing (oto-) and the bones of the spine (spondylo-), and enlarges the ends of bones (megaepiphyses).Penetrating atherosclerotic ulcer: A penetrating atherosclerotic ulcer (PAU) is an atherosclerotic lesion that ulcerates, leading to a hematoma forming within the walls of the aorta.Osmotic controlled-release oral delivery system: OROS (Osmotic [Controlled] Release Oral [Delivery] System) is a controlled release oral drug delivery system in the form of a tablet. The tablet has a rigid water-permeable jacket with one or more laser drilled small holes.
(1/2654) Responses of human intestinal microvascular endothelial cells to Shiga toxins 1 and 2 and pathogenesis of hemorrhagic colitis.
Endothelial damage is characteristic of infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). Because Stx-mediated endothelial cell damage at the site of infection may lead to the characteristic hemorrhagic colitis of STEC infection, we compared the effects of Stx1 and Stx2 on primary and transformed human intestinal microvascular endothelial cells (HIMEC) to those on macrovascular endothelial cells from human saphenous vein (HSVEC). Adhesion molecule, interleukin-8 (IL-8), and Stx receptor expression, the effects of cytokine activation and Stx toxins on these responses, and Stx1 and Stx2 binding kinetics and bioactivity were measured. Adhesion molecule and IL-8 expression increased in activated HIMEC, but these responses were blunted in the presence of toxin, especially in the presence of Stx1. In contrast to HSVEC, unstimulated HIMEC constitutively expressed Stx receptor at high levels, bound large amounts of toxin, were highly sensitive to toxin, and were not further sensitized by cytokines. Although the binding capacities of HIMEC for Stx1 and Stx2 were comparable, the binding affinity of Stx1 to HIMEC was 50-fold greater than that of Stx2. Nonetheless, Stx2 was more toxic to HIMEC than an equivalent amount of Stx1. The decreased binding affinity and increased toxicity for HIMEC of Stx2 compared to those of Stx1 may be relevant to the preponderance of Stx2-producing STEC involved in the pathogenesis of hemorrhagic colitis and its systemic complications. The differences between primary and transformed HIMEC in these responses were negligible. We conclude that transformed HIMEC lines could represent a simple physiologically relevant model to study the role of Stx in the pathogenesis of hemorrhagic colitis. (+info)
(2/2654) Tissue distribution of dextran sulfate sodium (DSS) in the acute phase of murine DSS-induced colitis.
In the present study, we examined histochemically the tissue distribution of dextran sulfate sodium (DSS) in the acute phase of murine colitis induced by administering DSS in the drinking water. DSS was mainly observed in the Kupffer cells of the liver, in the macrophages of the mesenteric lymph node (MLN) and in the lamina propria of the large intestine after administration of DSS. We followed the time course of DSS distribution and found that DSS, which was considered as a large and negatively charged molecule that can not easily cross membranes, was distributed in the liver, the MLN, and the large intestine 1 day after the start of administration of DSS. (+info)
(3/2654) Protein kinase C mediates experimental colitis in the rat.
Protein kinase C (PKC) plays an important role in the cell signal transduction of many physiological processes. In contrast to these physiological responses, increases in PKC activity have also been associated with inflammatory disease states, including ulcerative colitis. The objective of this study was to examine the role of PKC as a causative mediator in initiation of experimentally induced colitis in the rat. Colitis was induced in rats by intrarectal (0.6 ml) instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS; 75 mg/kg in 50% ethanol) or the PKC activator phorbol 12-myristate 13-acetate (PMA; 1.5-3.0 mg/kg in 20% ethanol). Gross and histological mucosal damage, mucosal neutrophil infiltration, mucosal PKC activity, and PKC protein content for PKC isoforms alpha, beta, delta, and epsilon were assessed 2 h to 14 days after an inflammatory challenge. Both PKC activity and mucosal injury increased significantly within 4 h of TNBS treatment. PKC activity was maximal at 7 days and declined at 14 days, whereas mucosal damage became maximal at 1 day and declined after 7 days. In contrast, neutrophil infiltration as assessed by myeloperoxidase activity only increased 12 h after TNBS treatment, became maximal 1 day after TNBS administration, and declined thereafter. PKCbeta, -delta, and -epsilon were increased in response to TNBS, whereas PKCalpha protein content was decreased. The PKC antagonists staurosporine and GF-109203X (25 ng/kg iv) reduced TNBS-induced changes in mucosal PKC activity and the degree of mucosal damage. In contrast, neutropenia induced by antineutrophil serum treatment did not significantly affect the degree of injury or mucosal PKC activity. Furthermore, activation of mucosal PKC activity with PMA also induced mucosal damage, which was also inhibited by pretreatment with a PKC antagonist. In conclusion, these results suggest that increases in PKC activity play a causative role in TNBS-induced colitis. The PKC-mediated response to TNBS does not appear to involve neutrophil infiltration. (+info)
(4/2654) Prolonged colonic epithelial hyporesponsiveness after colitis: role of inducible nitric oxide synthase.
Colonic epithelial secretion is an important host defense mechanism. We examined whether a bout of colitis would produce long-lasting changes in epithelial function that persisted after resolution of mucosal inflammation. Colitis was induced in rats with intracolonic trinitrobenzenesulfonic acid. Six weeks later, colonic damage and inducible nitric oxide synthase (iNOS) mRNA expression and activity were measured. Segments of distal colon were mounted in Ussing chambers for measurement of permeability and responsiveness to secretory stimuli. Basal electrolyte transport parameters and permeability were not different from untreated controls. Despite normal macroscopic and histological appearance, secretory responses to electrical field stimulation (EFS), isobutylmethylxanthine (IBMX), and carbachol were significantly depressed (by 60-70%) relative to controls. iNOS mRNA expression and enzyme activity were significantly elevated. Dexamethasone reversed epithelial hyporesponsiveness and significantly reduced iNOS mRNA expression. A selective iNOS inhibitor normalized the secretory responses to EFS and IBMX but not to carbachol. These data suggest that ongoing synthesis of nitric oxide by iNOS contributes to chronic suppression of epithelial secretory function after episodes of colitis. (+info)
(5/2654) Neurotensin is a proinflammatory neuropeptide in colonic inflammation.
The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous colitis in humans. In animal models, toxin A causes an acute inflammatory response characterized by activation of sensory neurons and intestinal nerves and immune cells of the lamina propria. Here we show that neurotensin and its receptor are elevated in the rat colonic mucosa following toxin A administration. Pretreatment of rats with the neurotensin receptor antagonist SR-48, 692 inhibits toxin A-induced changes in colonic secretion, mucosal permeability, and histologic damage. Exposure of colonic explants to toxin A or neurotensin causes mast cell degranulation, which is inhibited by SR-48,692. Because substance P was previously shown to mediate mast cell activation, we examined whether substance P is involved in neurotensin-induced mast cell degranulation. Our results show that neurotensin-induced mast cell degranulation in colonic explants is inhibited by the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that colonic mast activation in response to neurotensin involves release of substance P. We conclude that neurotensin plays a key role in the pathogenesis of C. difficile-induced colonic inflammation and mast cell activation. (+info)
(6/2654) Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation.
The objective of this study was to quantify, in vivo, constitutive and tumor necrosis factor alpha (TNF-alpha)-enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in different tissues from healthy wild-type mice (C57BL/6) as well as interleukin-10 (IL-10)-deficient mice with and without active colitis. Using the dual radiolabel monoclonal antibody technique, we found substantial constitutive expression of MAdCAM-1 in the intestine, colon, and mesenteric lymph nodes. MAdCAM-1 expression in these tissues was significantly enhanced, in a time-dependent manner, by systemic administration of TNF-alpha. Maximum surface expression was observed at 18 h after TNF-alpha administration and remained significantly elevated at 48 h post-TNF-alpha injection. No significant constitutive nor TNF-alpha-induced expression of MAdCAM-1 was detected in skeletal muscle, brain, or heart. In IL-10-deficient (IL-10 k/o) mice with no clinical or histological evidence of colitis, constitutive and TNF-alpha-induced expression of MAdCAM-1 in the intestine, cecum, and colon was not different from those values obtained with healthy wild-type controls. IL-10-deficient mice with active colitis exhibited a four- to fivefold greater expression of MAdCAM-1 in the cecum and colon compared with their healthy controls or to IL-10 k/o mice with no evidence of colitis. Taken together, these data demonstrate that TNF-alpha enhances surface expression of MAdCAM-1 in intestinal and colonic tissues to the same extent in both wild-type and IL-10 k/o mice with no colonic inflammation, whereas IL-10 k/o mice with active colitis exhibited a profound up-regulation of MAdCAM-1 in the colon. (+info)
(7/2654) A novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice.
A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated from the intestines of IL-10 (interleukin-10)-deficient (IL-10(-/-)) mice with inflammatory bowel disease. The organism was microaerobic, grew at 37 and 42 degrees C, and was oxidase and catalase positive but urease negative. On the basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria, the organism is classified as a novel helicobacter. Cesarean section-rederived IL-10(-/-) mice without helicobacter infection did not have histological evidence of intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter sp. developed variable degrees of inflammation in the lower intestine, and in immunocompetent mice, the experimental infection was accompanied by a corresponding elevated immunoglobulin G antibody response to the novel Helicobacter sp. antigen. These data support other recent studies which demonstrate that multiple Helicobacter spp. in both naturally and experimentally infected mice can induce inflammatory bowel disease. The mouse model of helicobacter-associated intestinal inflammation should prove valuable in understanding how specific microbial antigens influence a complex disease process. (+info)
(8/2654) Immediate-early gene expression in the inferior mesenteric ganglion and colonic myenteric plexus of the guinea pig.
Activation of neurons in the inferior mesenteric ganglion (IMG) was assessed using c-fos, JunB, and c-Jun expression in the guinea pig IMG and colonic myenteric plexus during mechanosensory stimulation and acute colitis in normal and capsaicin-treated animals. Intracolonic saline or 2% acetic acid was administered, and mechanosensory stimulation was performed by passage of a small (0.5 cm) balloon either 4 or 24 hr later. Lower doses of capsaicin or vehicle were used to activate primary afferent fibers during balloon passage. c-Jun did not respond to any of the stimuli in the study. c-fos and JunB were absent from the IMG and myenteric plexus of untreated and saline-treated animals. Acetic acid induced acute colitis by 4 hr, which persisted for 24 hr, but c-fos was found only in enteric glia in the myenteric plexus and was absent from the IMG. Balloon passage induced c-fos and JunB in only a small subset of IMG neurons and no myenteric neurons. However, balloon passage induced c-fos and JunB in IMG neurons (notably those containing somatostatin) and the myenteric plexus of acetic acid-treated animals. After capsaicin treatment, c-fos and JunB induction by balloon passage was inhibited in the IMG, but there was enhanced c-fos expression in the myenteric plexus. c-fos and JunB induction by balloon stimulation was also mimicked by acute activation of capsaicin-sensitive nerves. These data suggest that colitis enhances reflex activity of the IMG by a mechanism that involves activation of both primary afferent fibers and the myenteric plexus. (+info)