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Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse.

BACKGROUND AND AIMS: Substance P (SP) release from sensory nerves induces neurogenic inflammation. Neutral endopeptidase (NEP) degrades SP, thereby limiting its proinflammatory effects. Intestinal inflammation following Trichinella spiralis infection markedly downregulates NEP, resulting in diminished SP degradation, with unknown functional consequences. We hypothesised that diminished expression of NEP would exacerbate T spiralis induced enteritis. METHODS: NEP knockout (NEP-/-) and wild-type (NEP+/+) mice were infected with T spiralis and studied at 6, 12, 24, and 48 hours post infection (PI). Tissue inflammation was quantified by computerised cell counting and myeloperoxidase activity (MPO). The leucocyte adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), and SP were assessed by immunohistochemistry. RESULTS: Before infection, the lack of NEP was not associated with changes in mucosal cellularity or MPO activity. Twelve hours PI, NEP-/- mice showed a 2.5-fold increase in MPO activity at a time when values in NEP+/+ mice were still within normal limits. MPO activity and cellularity peaked at 24 hours PI. This was accompanied by increased staining for both ICAM-1 and SP in NEP-/- mice. Infusion of rhNEP to NEP-/- mice significantly reduced MPO activity 24 hours PI. CONCLUSIONS: These findings demonstrate that NEP downregulates the early onset of nematode intestinal inflammation and that increased bioavailability of SP and overexpression of ICAM-1 in NEP-/- mice likely play a role in the earlier onset of intestinal inflammation.

Animals↗

Quantitative histology in giardiasis.

The Weibel graticule was used to assess quantitatively histological changes in proximal jejunal mucosal biopsies from patients with Giardia lamblia infections. Most had malabsorption. A group of patients who had mild abdominal symptoms but no intestinal infection and normal absorption were the controls. There were significant differences in mean surface area (SA) measurements between patients with giardiasis and severe malabsorption and controls (P less than 0.001) and infected patients with normal absorption (P less than 0.05). SA measurements correlated significantly with D-xylose excretion results (r = 0.55; P less than 0.01) and daily facal fat output (r = -0.61; P less than 0.001). Significant correlations between duration of symptoms and SA measurements (r = 0.43; P less than 0.05) and D-xylose excretion (r = 0.43; P less than 0.05) in giardiasis suggest that histological and functional impairment are maximal soon after infection and resolve in time. Treatment with metronidazole or mepacrine was associated with a significant increase in SA (P less than 0.05) in patients with severe malabsorption but there was little change in SA in a similar group of patients who received tetracycline. The Weibel graticule was found to be useful in assessing the severity of histological changes and in following changes after treatment.

Dietary Fats↗

Immunocytochemistry of mucosal changes in patients infected with the intestinal nematode Strongyloides stercoralis.

AIM: To investigate the immunopathological changes in duodenal tissues induced by strongyloidiasis and to relate these to degrees of clinical severity. METHODS: Tissues taken from 21 patients showing mild, moderate or severe symptoms of strongyloidiasis, and from non-infected controls, were sectioned and stained immunocytochemically for IgA, secretory component (SC) and HLA-DR. Immunopathology was assessed by changes in numbers, intensity and distribution of stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt hyperplasia. There was notable infiltration of the lamina propria by IgA positive plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was also associated with increased expression of SC and decreased expression of HLA-DR in epithelial cells. Changes in all parameters correlated with degree of clinical severity. CONCLUSIONS: Profound mucosal changes are induced by strongyloidiasis. Some are analogous to those seen in coeliac disease, but others seem quite unusual. It is likely that these changes are functionally related to the immunopathophysiological consequences of infection seen in patients with severe disease.

Adult↗

Pseudo-obstruction and a sprue-like syndrome from stronglyloidiasis.

Symptomatic disease from Strongyloides stercoralis has been recognized for the first time in Trinidad. Five cases are reported, all showing clinical features suggestive of a sprue-like syndrome. Subtotal jejunal villous atrophy was seen in one case and partial villous atrophy in two. Three patients had laparotomies because of suspected partial intestinal obstruction. A sprue-like syndrome in certain Caribbean immigrants should arouse a suspicion of S. stercoralis.

Adult↗

Incidence of Anoplocephala perfoliata in horses examined at an Irish abattoir.

The intestinal tracts of 363 horses were examined after slaughter at a horse abattoir. The presence or absence of Anoplocephala perfoliata and the sites of attachment were recorded. A total of 51 per cent of the horses had A perfoliata attached to the mucosa of the ileocaecal junction and/or to the caecal mucosa; 5 per cent of the horses had A perfoliata attached only to the mucosa of the ileocaecal junction, 24 per cent had A perfoliata attached only to the caecal mucosa and 22 per cent of the horses had A perfoliata attached at both sites. The degree of infestation did not appear to be influenced by the season or by the age, breed or source of origin of the horses. The lesions at the sites of attachment included congestion, oedema, ulceration, diphtheresis, mucosal thickening, eosinophil infiltration and fibroplasia. The severity of the lesions was exacerbated by increasing numbers of worms.

Abattoirs↗

Intestinal anisakiasis: US in diagnosis.

Eighteen consecutive patients with intestinal anisakiasis were studied with high-resolution ultrasound (US) and barium studies. US showed markedly thickened bowel loops associated with luminal narrowing, swelling of Kerckring folds, and decreased peristalsis. A small amount of ascitic fluid around the bowel loops was found, and cytologic examinations of the ascites revealed a dense infiltration of eosinophils. Barium studies demonstrated segmental mucosal edema of the small intestine: The most common site was the distal ileum, and the mean length of the edematous lesion was 19 cm. All patients underwent treatment of symptoms without laparotomy, and their symptoms disappeared by the eighth day after onset. Patients with acute abdominal symptoms should be asked about the intake of raw or undercooked fish. If the above US features are found, the diagnosis of intestinal anisakiasis must be seriously considered to avoid unnecessary surgical treatment.

Adult↗

Intestinal schistosomiasis japonica: CT-pathologic correlation.

PURPOSE: To study the pathologic basis of intestinal wall calcification caused by Schistosoma japonicum visualized with computed tomography (CT). MATERIALS AND METHODS: Twelve patients underwent CT of the abdomen to detect what pathologic examination proved to be schistosomiasis japonica. Eight intestinal specimens from five of the patients were subjected to radiography, and the pathologic and radiographic findings were correlated. RESULTS: CT demonstrated curvilinear or nodular calcification in the colon in 11 patients, in the appendix in two, and in the distal ileum in one. In five patients, calcifications resembling tram tracks were found in the sigmoid colon. Pathologic examination of the specimens showed calcified eggs of S japonicum deposited more extensively in the submucosa and subserosa than in the muscularis propria, which led to the tram-track appearance. CONCLUSION: The extensive curvilinear or tram-track calcification found in the colon in patients with schistosomiasis japonica is calcification of deposited eggs.

Aged↗

Ca2+ channel blockade by verapamil inhibits GMCs and diarrhea during small intestinal inflammation.

The aim of this study was to investigate whether the blockade of L-type Ca2+ channels with verapamil suppresses giant migrating contractions (GMCs) and therefore diarrhea during small intestinal inflammation. Small intestinal inflammation was induced by infection with the nematode Trichinella spiralis. T. spiralis infection alone significantly increased the frequency of GMCs and decreased the frequency of phase III activity in the small intestine for 9 days. The increased frequency of GMCs was associated with diarrhea. Immunohistochemical staining with specific antibodies indicated that the number of neutrophils and mast cells increased significantly in the jejunal lamina propria during T. spiralis infection. Only the neutrophils increased significantly in the muscularis externa of the jejunum. Myeloperoxidase (MPO) activity increased significantly in the jejunal and ileal lamina propria. Daily verapamil administration during T. spiralis infection significantly reduced the frequency of GMCs and diarrhea but had no further significant effect on the already reduced frequency of phase III activity. Verapamil administration, however, did not reduce MPO activity or immunocyte infiltration in the jejunum or ileum. We conclude that blockade of L-type Ca2+ channels selectively reduces the frequency of GMCs and therefore diarrhea during small intestinal inflammation. The decreased frequency of GMCs is not secondary to a reduction in the inflammatory response.

Animals↗

Inflammation-induced impairment of enteric nerve function in nematode-infected mice is macrophage dependent.

Trichinella spiralis infection in rodents is associated with suppression of ACh release from myenteric plexus that can be mimicked by macrophage-derived cytokines. We verified the presence of a macrophage infiltrate in the intestine during T. spiralis infection and determined the extent to which this cell type is responsible for the neural changes. C57BL/6 mice were infected with 375 T. spiralis larvae by gavage, and the presence of macrophages (F4/80 positive) in the jejunum was determined immunohistochemically. In another experiment, infected mice were treated intravenously with liposomes containing dichloromethylene diphosphonate (clodronate, Cl(2)MDP), which causes apoptosis of macrophages, and killed at postinfection day 6, and jejunal tissues were evaluated for the presence of F4/80-positive cells and for [(3)H]ACh release from the myenteric plexus. Infection caused an infiltration of F4/80-positive cells into the intestinal mucosa, muscle layers, and myenteric plexus region and a significant suppression of ACh release (50%). Depletion of F4/80-positive macrophages using Cl(2)MDP-containing liposomes prevented the suppression in [(3)H]ACh release, identifying macrophages as the cell type involved in the functional impairment of enteric cholinergic nerves.

Acetylcholine↗

Small bowel review: part I.

In the past year, there have been many advances in the area of small bowel physiology and pathology. More than 1500 papers were assessed in preparation for this review. Some were selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist. Relevant review articles have been highlighted, and important clinical learning points have been stressed. The topics are varied in scope, and wherever possible show a logical progression from basic physiology to pathophysiology to clinical disorders and management.

Bile Acids and Salts↗

Studies on the inhibition of rapid expulsion of Trichinella spiralis in rats.

A variety of inhibitors was examined for their ability to interfere with the expression of rapid expulsion (RE) of challenge Trichinella spiralis infections in rats. Inhibitors of immediate hypersensitivity, prostaglandin release, peristalsis, or complement function, did not impair RE when administered to immune rats. Induction of intestinal anaphylaxis against T. spiralis or ovalbumin by passive serum transfer to intestinally primed rats (prior infection with Heligmosomoides polygyrus) or administration of the histamine liberator 48/80 also failed to stimulate RE. In contrast, irradiation or cortisone treatment 1, 3 or 5 days before challenge inhibited RE. We conclude that immediate hypersensitivity is not the terminal mediator of RE and plays a minor role or none at all. The effects of cortisone and irradiation suggest a major involvement by lymphoid cells in the RE reaction.

Anaphylaxis↗