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Field evaluation of the effect of in-feed doxycycline for the control of ileitis in weaned piglets.

The aim of this trial was to evaluate the effect of in-feed doxycycline (DOXY) on the control of ileitis in weaned piglets. On a farm with a previous history of ileitis outbreaks, 288 piglets at the age of weaning (25 +/- 2 days old) were divided into four experimental groups, each group comprising three pens with 24 piglets in each pen. Non-medicated animals served as negative control (NC) group, whereas groups DOXY-50, DOXY-125 and DOXY-250 received doxycycline via feed at 50, 125 and 250 ppm, respectively. Therapy lasted for 14 days followed by an observation period of 28 days. In conclusion, administration of doxycycline at a dose rate of 125 or 250 ppm had beneficial effect compared with the NC group. in terms of the reduction of diarrhoea prevalence, the enhancement of growth performance and the reduction of prevalence of Lawsonia intracellularis in the intestine, as shown either by the PCR method or by specific histopathological examinations. Treatment with 250 ppm of doxycycline for a fortnight interval post-weaning seems to be beneficial leading to better growth rates of piglets not only during treatment period, but also throughout the whole nursery phase.

Animal Feed↗

Medium-chain triglycerides modulate ileitis induced by trinitrobenzene sulfonic acid.

BACKGROUND: It is important to develop an appropriate animal model for further investigation into inflammatory bowel disease (IBD). We therefore investigated a trinitrobenzene sulfonic acid (TNBS) ileitis model. Dietary fat in Crohn's disease is still a controversial risk factor for IBD. We therefore also studied the effects of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on TNBS ileitis. METHODS AND RESULTS: An intraileal injection of TNBS induced ulceration and inflammation with thickening of the intestinal wall, which were characterized histologically by infiltration of polymorphic nuclear leucocytes and by granuloma formation. The mucosal damage score and serum sialic acid levels reached their highest 7 days after the TNBS injection and then gradually decreased. The mucosal damage series in the MCT group was significantly lower than in the LCT group, and levels of tumour necrosis factor-alpha (TNF-alpha) and leukotriene B4 (LTB4) tended to be lower in the MCT group. CONCLUSIONS: These results suggested that TNBS enteritis might be useful as an IBD animal model and that MCT modulates intestinal inflammation and is less damaging than LCT.

Analysis of Variance↗

Antibody blockade of CCL25/CCR9 ameliorates early but not late chronic murine ileitis.

BACKGROUND & AIMS: CCL25 mediates the homeostatic recruitment of CCR9-expressing lymphocytes to the small intestine, but the function of this chemokine/receptor pair during chronic small intestinal inflammation has yet to be determined. Furthermore, although clinical trials to evaluate the efficacy of targeting the CCL25/CCR9 axis for the treatment of Crohn's disease are being conducted, preclinical data in animal models of IBD are lacking. METHODS: In the current studies, we investigated the expression of CCL25 and CCR9 as a function of disease progression in a spontaneous murine model of chronic ileitis (SAMP1/YitFc) using flow cytometry, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. In addition, we assessed the functional role of the axis in the overall disease process through therapeutic studies that target the chemokine or the receptor during early and late disease. RESULTS: The percentage of CCR9-expressing lymphocytes increased during early disease, accompanied by the appearance of a population of CCR9(high) lymphocytes, predominantly within CD8(+) T cells. Yet different from patients with primary sclerosing cholangitis, the expression of CCL25 remained restricted to the small intestine, even in mice with inflammation of the biliary tree. Neutralization of the receptor or the chemokine attenuated early disease but showed no therapeutic efficacy during the later stages, when overall CCR9 expression decreased and the CCR9(high) population was absent. CONCLUSIONS: Our studies show that the role of this chemokine axis is not limited to homeostatic recruitment, as previously believed. However, these molecules appear to play their most crucial role during the early stages of chronic murine ileitis.

Animals↗

Crohn's ileitis complicated by amyloidosis: observations and therapeutic considerations.

We present a patient with clinically asymptomatic amyloidosis associated with Crohn's ileitis. A distinction should be made between immunocytic dyscrasia associated with amyloidosis (formerly primary or myeloma-associated amyloidosis) and acquired systemic amyloidosis (formerly secondary amyloidosis). We compare the natural course of amyloidosis complicating Crohn's disease with these complicating familial Mediterranean fever (FMF), and discuss the role of resection and the rationale behind colchicine therapy. Our patient is the first reported case in which colchicine therapy alone has been successful in the prophylactic treatment of amyloidosis complicating Crohn's ileitis.

Adult↗

Postcolectomy ileitis.

A case is presented of a patient who had classic ulcerative colitis, both clinically and on detailed pathologic study, that underwent an ileo-pouch anal anastomosis and then developed pouchitis followed by ileitis. The patient has done fairly well on routine medications, but this case represents ileitis developing post colectomy that did not exist previous to colectomy and raises the questions for the following presentations and discussions in this workshop symposium.

Abdominal Pain↗

Comparative analysis of the 16S rRNA gene sequence of the putative agent of proliferative ileitis of hamsters.

Proliferative ileitis of hamsters is consistently associated with the presence of intracellular bacteria in affected ileal epithelial cells. The 16S rRNA gene sequence of the putative etiologic agent of proliferative ileitis was determined by using cell culture-maintained organisms. The highest level of relatedness (98.4%) was observed with a newly described obligately intracellular bacterium obtained from porcine intestines, and the level of homology with Desulfovibrio desulfuricans was 87.5%.

Animals↗

A distinctive aphthous ileitis linked to Ancylostoma caninum.

Ileal ulceration is diagnosed commonly at colonoscopy in northeastern Australia. This observation has occurred contemporaneously with the description of a painful enteritis caused through supposedly rare infections by Ancylostoma caninum, the cosmopolitan dog hookworm. In this study, we describe the morphology and prevalence of ileal ulcers and investigate their cause. There were 182 patients with a distinctive aphthous ileitis highlighted by haemorrhage into the tips of surrounding villi. The annual rate reached 4.7% of ileal examinations. Eosinophilic enteritis was the characteristic, but inconsistent, histological appearance. Ulceration was linked to infection by A. caninum through serological testing and, in three patients, by the retrieval of single hookworms. Affected patients were also more likely to own a dog (53%) than the total colonoscopic population (43%; P < 0.02). The monthly rates of diagnosis were related to climate with fewest recordings during winter. Pain was the chief indication for colonoscopy (49%), proportionally higher than in controls (28%; P < 0.0001). Patients with ulcers had increased blood eosinophil, immunoglobulin E and serological values. These results were higher still in the subset with pain compared with the rest. Most patients, however, had colonoscopy performed for unrelated reasons, such as bowel cancer surveillance, and were identified as having subclinical ulceration (rate 3.2%). The findings establish a distinctive aphthous ileitis characterized by tissue eosinophilia. The cause has been tentatively linked to canine hookworms. It is proposed that infection in this geographic region is common and only rarely does a painful enteritis develop as a consequence of hypersensitization.

Ancylostoma↗

Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons.

Intestinal inflammation induces hyperexcitability of dorsal root ganglia sensory neurons, which has been implicated in increased pain sensation. This study examined whether alteration of sodium (Na+) and/or potassium (K+) currents underlies this hyperexcitability. Ileitis was induced in guinea pig ileum with trinitrobenzene sulphonic acid (TBNS) and dorsal root ganglion neurons innervating the site of inflammation were identified by Fast Blue or DiI fluorescence labelling. Whole cell recordings were made from acutely dissociated small-sized neurons at 7-10 days. Neurons exhibited transient A-type and sustained outward rectifier K+ currents. Compared to control, both A-type and sustained K+ current densities were significantly reduced (42 and 34%, respectively; P < 0.05) in labelled neurons from the inflamed intestine but not in non-labelled neurons. A-type current voltage dependence of inactivation was negatively shifted in labelled inflamed intestine neurons. Neurons also exhibited tetrodotoxin-sensitive and resistant Na+ currents. Tetrodotoxin-resistant sodium currents were increased by 37% in labelled neurons from the inflamed intestine compared to control (P < 0.01), whereas unlabelled neurons were unaffected. The activation and inactivation curves of these currents were unchanged by inflammation. These data suggest ileitis increases excitability of intestinal sensory neurons by modulating multiple ionic channels. The lack of effect in non-labelled neurons suggests signalling originated at the nerve terminal rather than through circulating mediators and, given that Na+ currents are enhanced whereas K+ currents are suppressed, one or more signalling pathways may be involved.

Animals↗

Ileitis after colectomy for ulcerative colitis or carcinoma.

An ileitis developing years or months after ileostomy was recognised and described many years ago but has rarely been mentioned since. We describe nine patients with a non-specific preanastomotic ileitis that developed years after colectomy in patients operated on for ulcerative colitis or carcinoma. The disease developed after various types of reconstruction: ileorectal, ileoanal, with or without pouch. The diseased ileum showed inflammation, erosions, ulcerations, and sometimes strictures. The disease course ranged from asymptomatic to severe pain and diarrhoea. No specific cause could be shown. Granulomas, infectious agents or ischaemic changes were not found. The anastomosis was always patent. Three patients have had numerous episodes of intestinal obstruction presumably because of adhesions. Seven of nine patients were female. The response to steroids, 5-aminosalicylic acid preparations, and methotrexate was poor, three patients responded well to azathioprine. The condition is not rare and the cause remains unknown.

Adult↗

Alterations in capsaicin-evoked electrolyte transport during the evolution of guinea pig TNBS ileitis.

The efferent secretomotor activity of capsaicin-sensitive nerves was monitored during the evolution of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis in the guinea pig by recording changes in short-circuit current (DeltaI(sc)) in response to capsaicin, substance P (SP), and carbachol. Submucosal-mucosal preparations mounted in standard Ussing chambers were studied at time 0, at 8 h, and 1, 3, 5, 7, 14, and 30 days following the intraluminal instillation of TNBS or saline. Maximal DeltaI(sc) responses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated DeltaI(sc) were also significantly reduced. Similar attenuation in capsaicin and carbachol responses was observed in jejunal tissue 20 cm proximal to the inflamed site at day 7. These studies demonstrate that efferent secretomotor function of capsaicin-sensitive nerves is maintained early in TNBS ileitis but significantly reduced by 24 h. By day 7, defects in enterocyte secretory function at inflamed and noninflamed sites also occurred, an effect that may be mediated by circulating cytokines.

Anesthetics, Local↗

TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons.

This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12-24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 microm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls (P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group (P < 0.05). The number of action potentials discharged increased in the TNBS group (P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na(+) and K(+) channels at the soma, which persist after removal from the inflamed environment.

4-Aminopyridine↗

Mechanism of glucocorticoid-mediated reversal of inhibition of Cl(-)/HCO(-)(3) exchange during chronic ileitis.

In the normal ileum, coupled NaCl absorption occurs via the dual operation of Na(+)/H(+) and Cl(-)/HCO(-)(3) exchange on the brush-border membrane (BBM) of villus cells. In a rabbit model of chronic small intestinal inflammation we determined the cellular mechanism of inhibition of NaCl absorption and the effect of steroids on this inhibition. Cl(-)/HCO(-)(3) but not Na(+)/H(+) exchange was reduced in the BBM of villus cells during chronic ileitis. Cl(-)/HCO(-)(3) exchange was inhibited secondary to a decrease in the affinity for Cl(-) rather than an alteration in the maximal rate of uptake of Cl(-) (V(max)). Methylprednisolone (MP) stimulated Cl(-)/HCO(-)(3) exchange in the normal ileum by increasing the V(max) of Cl(-) uptake rather than altering affinity for Cl(-). MP reversed the inhibition of Cl(-)/HCO(-)(3) exchange in rabbits with chronic ileitis. However, MP alleviated the Cl(-)/HCO(-)(3) exchange inhibition by restoring the affinity for Cl(-) rather than altering the V(max) of Cl(-) uptake. These data suggest that glucocorticoids mediate the alleviation of Cl(-)/HCO(-)(3) exchange inhibition in chronically inflamed ileum by reversing the same mechanism that was responsible for inhibition of this transporter rather than exerting a direct effect on the transporter itself, as was the case in normal ileum.

Animals↗

Potential role of histamine monochloramine in a rabbit model of ileitis.

Histamine chloramines, derived from the chlorination of histamine by granulocyte-derived oxidants, are potential mediators of intestinal injury and dysfunction in states of atopy or inflammation. We assessed the ability of histamine monochloramine to increase epithelial permeability in rabbit distal small intestine and determined whether the conditions for histamine chloramine formation are favorable in a rabbit model of ileitis. Epithelial permeability, quantified by the blood-to-lumen clearance of 51Cr-labeled ethylenediaminetetraacetic acid, was enhanced by luminal perfusion with either histamine or histamine monochloramine (10 microM), although the latter was twice as effective (p less than 0.05). In a rabbit model of ileitis induced by a luminal solution of acetic acid (200 mM) and casein (10 mg/ml) there was a marked increase in epithelial permeability and in the release into the lumen of histamine, myeloperoxidase, 6-keto-prostaglandin F1 alpha and protein. These results suggest that the conditions are favorable for histamine chloramine formation and that histamine and histamine chloramine may impair the integrity of the epithelial barrier.

Acute Disease↗

Terminal ileitis associated with Blastocystis hominis infection.

We report on the previously unobserved clinical presentation of terminal ileitis secondary to Blastocystis hominis in a 37-yr-old white male. When the patient was treated with metronidazole, the symptoms improved and the radiographic abnormalities resolved. We believe that this is the first well-documented instance of terminal ileitis secondary to B. hominis.

Adult↗

Amelioration of chronic ileitis by nitric oxide synthase inhibition.

Nitric oxide synthesis appears to be elevated in inflammatory bowel disease, but little is known about the contribution of nitric oxide to the pathophysiological process. To address this issue, we included the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (10 or 100 micrograms/ml) of guinea pigs immediately after induction of ileitis by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol). Guinea pigs were sacrificed after 7 days of this ad libitum treatment. Control groups received either intraluminal TNBS, saline or ethanol (TNBS vehicle) without L-NAME or TNBS + D-NAME (100 micrograms/ml), the inactive enantiomer. Immediately before sacrifice, guinea pigs were anesthetized and saline was administered intraluminally at the site of TNBS or saline administration and then withdrawn after 30 min. Change in lavage volume and lavage protein and nitrite levels were measured, as well as tissue myeloperoxidase and bowel wall thickness (weight/length). TNBS administration resulted in an increase in tissue thickness, myeloperoxidase and lavage protein and nitrite levels over sham controls. Oral L-NAME prevented these responses. D-NAME was ineffective with the exception of tissue thickness. The change in intestinal lavage fluid volume indicated that reabsorptive processes dominated in the sham and TNBS + L-NAME groups, and secretory responses predominated in TNBS and TNBS + D-NAME animals. In contrast to TNBS-induced ileitis, L-NAME (100 micrograms/ml, p.o., 7 days) administration to intact animals resulted in a local inflammatory response (i.e., increased myeloperoxidase activity and a fluid secretory response).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

[Acute ileitis due to Ascaris lumbricoides].

The authors report their experience of two cases of acute ileitis with an obstructive complication due to "Ascaris lumbricoides". The distinctive features were, in the first case, the pathogenic mechanism responsible of the occlusion, and in the second one, the need of a long term follow-up. The latter, especially in the "aspecific forms", often allows an etiological diagnosis difficult even at laparotomy. Indicating the most frequent causes of surgical complications found in ileitis, which is a medical disease easily curable by medical and dietetic means, the authors confirm the difficulties of an etiological diagnosis and surgical treatment, increased by the rarity of the disease.

Abdomen, Acute↗

[Acute terminal ileitis and Crohn's disease].

The finding of acute inflammation of the terminal ileus frequently leads to differential diagnostic reflections whether it is the first stage of Crohn's disease or acute ileitis with a different aetiology. At the Surgical Clinic of the Third Medical Faculty in Prague 10 in 1981-1992 21 patients with this condition were hospitalized and operated. Crohn's disease developed subsequently only in six patients and in five of them the development of the disease called for another operation. The remaining 15 patients are free from clinical complaints. The mean age of these patients at the time of operation was 30.4 years, the mean length of the gut affection was 9.7 cm, the mean follow up period is 6.4 years. The author analyzes possible causes of these cases of ileitis and discusses the relationship with Crohn's disease.

Acute Disease↗

Guinea pig ileitis is attenuated by the leumedin N-(fluorenyl-9- methoxycarbonyl)-leucine (NPC 15199).

Anti-inflammatory properties have been ascribed to a series of N-(fluorenyl-9-methoxycarbonyl) amino acids called leumedins that inhibit the activity of granulocytes and T-lymphocytes. We evaluated one of these leumedins, N-(fluorenyl-9-methoxycarbonyl) leucine (NPC 15199), in a model of ileitis in guinea pigs. Ileitis was induced by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol) in anesthetized guinea pigs. NPC 15199 was administered daily (10 or 100 mg/kg, s.c.). After 7 days, the guinea pigs were anesthetized, and saline was administered intraluminally into an ileal loop created at the site of TNBS administration and was withdrawn after 30 min. The changes in lavage protein, nitrite levels, myeloperoxidase (MPO) activity and mast cell numbers were used as indices of inflammation and injury. NPC 15199 (10 or 100 mg/kg) attenuated or abolished TNBS-induced elevations in lavage protein and nitrite content. Only the high dose of NPC 15199 (100 mg/kg) attenuated ileal MPO activity and mast cell hyperplasia. Histological disturbances induced by TNBS administration included crypt hypertrophy, mucosal and submucosal fibrosis and smooth-muscle hyperplasia. These disturbances were reversed by high-dose NPC 15199 (100 mg/kg) but were minimally affected by low-dose NPC 15199 (10 mg/kg). We conclude that NPC 15199 prevents mucosal injury and dysfunction in this model of intestinal inflammation. Inhibition of granulocyte infiltration does not appear to be essential for the beneficial effects of NPC 15199 and suggests that the alternative actions of NPC 15199 may be pertinent to this model.

Animals↗