Villus Atrophy Research Articles

Studies of the small bowel surface by scanning electron microscopy in infants with persistent diarrhea.

We describe the ultrastructural abnormalities of the small bowel surface in 16 infants with persistent diarrhea. The age range of the patients was 2 to 10 months, mean 4.8 months. All patients had diarrhea lasting 14 or more days. Bacterial overgrowth of the colonic microflora in the jejunal secretion, at concentrations above 10(4) colonies/ml, was present in 11 (68.7%) patients. The stool culture was positive for an enteropathogenic agent in 8 (50.0%) patients: for EPEC O111 in 2, EPEC O119 in 1, EAEC in 1, and Shigella flexneri in 1; mixed infections due to EPEC O111 and EAEC in 1 patient, EPEC O119 and EAEC in 1 and EPEC O55, EPEC O111, EAEC and Shigella sonnei in 1. Morphological abnormalities in the small bowel mucosa were observed in all 16 patients, varying in intensity from moderate 9 (56.3%) to severe 7 (43.7%). The scanning electron microscopic study of small bowel biopsies from these subjects showed several surface abnormalities. At low magnification (100X) most of the villi showed mild to moderate stunting, but on several occasions there was subtotal villus atrophy. At higher magnification (7,500X) photomicrographs showed derangement of the enterocytes; on several occasions the cell borders were not clearly defined and very often microvilli were decreased in number and height; in some areas there was a total disappearance of the microvilli. In half of the patients a mucus-fibrinoid pseudomembrane was seen partially coating the enterocytes, a finding that provides additional information on the pathophysiology of persistent diarrhea.

Intestinal development of early-weaned piglets receiving diets supplemented with selected amino acids or polyamines

Early-weaned piglets are subjected to various environmental and nutritional stresses that can result in overall poor performance. Several amino acids associated with the urea cycle have been shown to be critical to intestinal development and metabolism. The objective of this research was to examine performance and intestinal development in early-weaned piglets receiving diets supplemented with selected amino acids or polyamines. Forty-two Yorkshire piglets (3.94 ± 0.43 kg) weaned at ~12.5 d were randomly assigned to diets supplemented with either arginine, glutamate, citrulline, ornithine or polyamines, at levels of 0.93, 6.51, 0.94, 0.90 and 0.39%, respectively. Diets were fed for 12 d and various parameters to assess growth and intestinal development were measured. Glutamate supplementation enhanced both total and mucosal growth in several sections of the small intestine (P < 0.05), whereas polyamines were detrimental to intestinal growth. Arginine and glutamate supplementation prevented weaning-induced villus atrophy in the duodenum, compared with both the control and polyamine-fed pigs (P = 0.004). These results indicate that glutamate and arginine supplementation may enhance intestinal development of the early-weaned piglet, whereas polyamine supplementation at the ratios and concentrations used in this experiment is not recommended in typical early-weaned piglet diets. Key words: Early-weaning, amino acids, piglet, polyamine, small intestine, development

Human leukocyte antigen class II alleles in white Brazilian patients with celiac disease.

Celiac disease (CD) is a permanent gluten intolerance disorder characterized by malabsorption, intestinal mucosa villus atrophy, and crypt hyperplasia. Clinical and histologic features improve in persons consuming a gluten free diet. The pathogenesis of CD involves environmental, genetic, and immunologic factors. The frequencies of human leukocyte antigen (HLA) class II alleles were evaluated in white Brazilian patients who had CD and compared with those observed in healthy individuals from the same geographical area (Ribeirão Preto, São Paulo) and of similar ethnic background. Twenty-five patients with CD, 11 females and 14 males, and 91 control individuals were studied. The HLA class II alleles were typed using amplified DNA hybridized with sequence-specific primers. Statistical analysis was performed using the two-tailed Fisher exact test. The relative risk (RR), etiologic fraction (EF), and preventive fraction (PF) were also estimated. The EF represents the attributable risk for the development of CD at the population level, whereas PF represents the protective risk. The frequency of the HLA-DRB1*03, HLA-DRB1*07, and HLA-DQB1*02 alleles was significantly increased in patients. The RR conferred by these alleles was 5.35, 7.15, and 10.6, respectively, and the EF was 48.7%, 44.7%, and 76%, respectively. The frequency of HLA-DQB1*06 alleles was significantly decreased in CD patients, conferring an RR of 0.08 and a PF of 48%. The results show that HLA-DRB1*03, HLA-DRB1*07, and HLA-DQB1*02 alleles conferred susceptibility to CD in Brazilian patients. In contrast, HLADQB1*06 alleles conferred protection against development of the disease.

Human Leukocyte Antigen Class II Alleles in White Brazilian Patients With Celiac Disease

ABSTRACTBackgroundCeliac disease (CD) is a permanent gluten intolerance disorder characterized by malabsorption, intestinal mucosa villus atrophy, and crypt hyperplasia. Clinical and histologic features improve in persons consuming a gluten free diet. The pathogenesis of CD involves environmental, genetic, and immunologic factors.MethodsThe frequencies of human leukocyte antigen (HLA) class II alleles were evaluated in white Brazilian patients who had CD and compared with those observed in healthy individuals from the same geographical area (Ribeirão Preto, São Paulo) and of similar ethnic background. Twenty‐five patients with CD, 11 females and 14 males, and 91 control individuals were studied. The HLA class II alleles were typed using amplified DNA hybridized with sequence‐specific primers. Statistical analysis was performed using the two‐tailed Fisher exact test. The relative risk (RR), etiologic fraction (EF), and preventive fraction (PF) were also estimated. The EF represents the attributable risk for the development of CD at the population level, whereas PF represents the protective risk.ResultsThe frequency of the HLA‐DRB1*03, HLA‐DRB1*07, and HLA‐DQB1*02 alleles was significantly increased in patients. The RR conferred by these alleles was 5.35, 7.15, and 10.6, respectively, and the EF was 48.7%, 44.7%, and 76%, respectively. The frequency of HLADQB1*06 alleles was significantly decreased in CD patients, conferring an RR of 0.08 and a PF of 48%.ConclusionsThe results show that HLA‐DRB1*03, HLA‐DRB1*07, and HLA‐DQB1*02 alleles conferred susceptibility to CD in Brazilian patients. In contrast, HLADQB1*06 alleles conferred protection against development of the disease.

Postnatal adaptation of the gastrointestinal tract in neonatal pigs: a possible role of milk-borne growth factors

During the postnatal period the gastrointestinal (GI) tract of the neonatal pig encounters numerous challenges and severe stress, particularly at the time of birth and weaning. In response to such challenges, the GI tract undergoes marked changes, including accelerated tissue growth and functional maturation during the immediate postnatal period, and intestinal villus atrophy and damage following weaning. The changes are apparently related to the onset of colostrum ingestion at the time of birth and the withdrawal of milk ingestion at the time of weaning. Porcine colostrum and milk contain not only highly digestible nutrients but also numerous bioactive compounds, including various types of growth factors, including epidermal growth factor, insulin-like growth factor-I (IGF-I), IGF-II, insulin and transforming growth factor-β. Experimental evidence summarized in the review indicates a regulatory role of these milk-borne growth factors in stimulating GI tissue growth and function maturation, and in enhancing repair of damaged GI mucosa in the suckling young. The findings imply that milk-borne growth factors may be used to enhance GI maturation in neonatal animals and be used to treat GI mucosal damages. Potential therapeutic applications of milk-borne growth factors in both agricultural animals and human infants warrant further investigation.

Intestinal lesions caused by a strain of Chlamydia suis in weanling pigs infected at 21 days of age.

The objective of this study was to determine whether a strain of Chlamydia suis shown previously to be an intestinal pathogen in gnotobiotic piglets could cause diarrhea and intestinal lesions in young weanling pigs. Pigs from 2 sows were randomly assigned to 2 groups. Group 1 included 13 pigs that were weaned at 24 hours of age and then housed in isolator units and fed milk replacer and unmedicated starter ration. Group 2 included 8 pigs that nursed their respective sows, consumed unmedicated starter ration, and were weaned at 21 days of age. Ten pigs in group 1 and 6 pigs in group 2 were inoculated orally with 4 x 108 inclusion-forming units of C. suis strain R27 at 21 days of age. Control pigs were inoculated with sham inoculum. The pigs were necropsied 5-14 days postinoculation (DPI). None of the Chlamydia-infected pigs developed diarrhea. Villus atrophy was seen histologically in sections of ileum from Chlamydia-infected pigs in both groups 5 and 7 days DPI. Lymphangitis and multiple lymphohistiocytic and neutrophilic aggregates were seen in the submucosa, tunica muscularis, and serosa of the distal jejunum, ileum, and colon from Chlamydia-infected pigs in both groups 5-14 DPI. Immunostaining of sections of distal jejunum, ileum, and colon from infected pigs revealed chlamydial antigen in intestinal epithelium and in foci of lymphangitis/inflammation. The results indicated that C. suis strain R27 can cause intestinal lesions in young weanling pigs, and the lesions are similar to those seen in gnotobiotic piglets. The results also indicated that strain R27 causes asymptomatic intestinal infections in young weanling pigs, at least under the conditions of this study.

Herbal therapies used by patients for inflammatory bowel disease are antioxidant in vitro

The Ileo Neo-Rectal Anastomosis (lNRA) is an alternative restorative procedure for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) and has been developed in order to reduce the high pouch-related complication (15-35%) and failure rate (6.5%) of the Ileo Pouch-Anal Anastomosis (IPAA). In contrast to IPAA the ano-rectum is preserved and the rectal mucosa is excised and replaced by healthy, vascularised, ileal mucosa. The ultimate purpose, establishment of a compliant neo-rectal reservoir with a concordant low defecation frequency and full continence in the long-term is being addressed in this presentation. In 12 patients (10 UC + 2 FAP) an INRA was performed after subtotal colectomy, with a temporary diverting ileostomy for three months. Anorectal function was tested preoperatively and up to a median of 16 months postoperatively (range 12-22 months). The first sensation, urge sensation, capacity, compliance and anorectal electrosensibility were measured. Anal and rectal ultrasound were carried out to assess the transmural architecture of the neo-rectum. Furthermore histological aspects of neo-rectal mucosa ingrowth and maturation were assessed. The INRA procedure was successfully performed in all patients. Ano-rectal function tests revealed no change in anal sphincter resting (median 8 (6-13) kPa) and squeeze pressure (median 18 (7-35) kPa). Rectal capacity temorarily decreased considerably after INRA, but increased up to normal levels in 12 months (median 108 (56-300) vs 157 (130-225) ml, respectively). This is in accordance with increasing compliance of the neorectum and decreasing stoolfrequency. Anal electrosensibility was unchanged after INRA (median 7 (4-14) rnA), but rectal electrosensibility decreased from median 26 rnA (16-75) to 46 rnA (13-99). Ultrasound showed no structural damage to the anal sphincter and an anatomically normal intestinal wall. Histology showed villus atrophy and a mixed active and chronic inflammatory infiltrate at 6 weeks with recovery in time. At 6 months the villus architecture was restored with an intact goblet cell population and brush border and dissapearance of the inflammatory infiltrate. Although during the INRA procedure the anorectum is manipulated to great extend, anorectal function is perserved. Anorectal function, as well as the functional result after INRA are comparable to IPAA. Ileal mucosa transplantation is feasible with development of healthy neorectal mucosa.

Villus atrophy in a mouse model of total parenteral nutrition: Apoptosis as a cause and potential mechanisms

Villus atrophy in a mouse model of total parenteral nutrition: Apoptosis as a cause and potential mechanisms

Herbal therapies used by patients for inflammatory bowel disease are antioxidant in vitro

The Ileo Neo-Rectal Anastomosis (lNRA) is an alternative restorative procedure for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) and has been developed in order to reduce the high pouch-related complication (15-35%) and failure rate (6.5%) of the Ileo Pouch-Anal Anastomosis (IPAA). In contrast to IPAA the ano-rectum is preserved and the rectal mucosa is excised and replaced by healthy, vascularised, ileal mucosa. The ultimate purpose, establishment of a compliant neo-rectal reservoir with a concordant low defecation frequency and full continence in the long-term is being addressed in this presentation. In 12 patients (10 UC + 2 FAP) an INRA was performed after subtotal colectomy, with a temporary diverting ileostomy for three months. Anorectal function was tested preoperatively and up to a median of 16 months postoperatively (range 12-22 months). The first sensation, urge sensation, capacity, compliance and anorectal electrosensibility were measured. Anal and rectal ultrasound were carried out to assess the transmural architecture of the neo-rectum. Furthermore histological aspects of neo-rectal mucosa ingrowth and maturation were assessed. The INRA procedure was successfully performed in all patients. Ano-rectal function tests revealed no change in anal sphincter resting (median 8 (6-13) kPa) and squeeze pressure (median 18 (7-35) kPa). Rectal capacity temorarily decreased considerably after INRA, but increased up to normal levels in 12 months (median 108 (56-300) vs 157 (130-225) ml, respectively). This is in accordance with increasing compliance of the neorectum and decreasing stoolfrequency. Anal electrosensibility was unchanged after INRA (median 7 (4-14) rnA), but rectal electrosensibility decreased from median 26 rnA (16-75) to 46 rnA (13-99). Ultrasound showed no structural damage to the anal sphincter and an anatomically normal intestinal wall. Histology showed villus atrophy and a mixed active and chronic inflammatory infiltrate at 6 weeks with recovery in time. At 6 months the villus architecture was restored with an intact goblet cell population and brush border and dissapearance of the inflammatory infiltrate. Although during the INRA procedure the anorectum is manipulated to great extend, anorectal function is perserved. Anorectal function, as well as the functional result after INRA are comparable to IPAA. Ileal mucosa transplantation is feasible with development of healthy neorectal mucosa.

Inheritance of gluten-sensitive enteropathy in Irish Setters.

To establish a model for inheritance of gluten-sensitive enteropathy (GSE) in Irish Setters. 44 dogs of a 6-generation family of Irish Setters with GSE and 7 healthy Irish Setters. Phenotype of each dog was determined after oral administration of gluten in the weaning diet, using morphometric evaluation of jejunal biopsies (all generations) and measurement of small intestinal permeability by use of a lactulose-rhamnose permeation test (generations 1, 2, and 3). Overall probability for each of 4 genetic models of inheritance (autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant) accounting for segregation of partial villus atrophy within the entire family was calculated. The autosomal recessive model was most tenable and was 56,250 times more likely to account for segregation of partial villus atrophy than the autosomal dominant model, assuming disease prevalence of 0.8%. Both sex-linked models were untenable. These conclusions were robust to the error attached to estimation of disease prevalence. High intestinal permeability without morphometric jejunal abnormalities in 4 of 20 dogs in the 3 youngest generations suggested heterogeneity of lesions associated with GSE. Genetic transmission of GSE is under the control of a single major autosomal recessive locus.

Pressure and frequency dependent linkage between motility and epithelial secretion in human proximal small intestine

BACKGROUNDMotor disturbances are sometimes associated with diarrhoea by unknown mechanisms.AIMTo determine if there is a quantitative link between intestinal motility and epithelial secretion.SUBJECTSExperiments were performed in 21 healthy volunteers and...

The impact of infection and nutrition on gut function and growth in childhood.

Poor growth performance during infancy and early childhood is a frequent fact of life in most developing countries. Work in The Gambia has demonstrated that more than 43 % of observed growth faltering during the first 15 months of life can be explained by the presence of a mucosal enteropathy in the small intestine. Within communities the illness is very common: in the area investigated more than 95 % of infants above 8 months of age were affected, and on average they suffered a growth-limiting enteropathy for more than 75 % of their first year of life. Two mechanisms of weight loss have been defined. First, partial villus atrophy reduces absorption and digestion of lactose and probably other nutrients. Second, and more importantly, damage to the mucosal barrier allows translocation of macromolecules into the mucosa and blood, triggering both local and systemic immune and inflammatory mechanisms. Given the severity of the enteropathy it is not surprising that infants fail to grow at a normal rate. Recent findings suggest that these lesions continue throughout childhood and into adulthood. Thus, a persistence of chronic, local and systemic inflammation throughout childhood may be responsible for continued poor growth during this period. Although the nature of the enteropathy and the mechanisms of growth failure have been defined, the factors involved in the initiation and persistence of the intestinal lesion remain uncertain, making clinical management difficult. More work is clearly required to elucidate these factors and to define interventions to prevent or treat the enteropathy.

Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis.

Chemotherapy or radiotherapy often cause mucosal damage in the gut (gut mucositis) in cancer patients. As a step to investigate mechanisms underlying subsequent intestinal repair, we have examined the expression profiles of hepatocyte growth factor (HGF) and its receptor c-met, two molecules previously implicated in tissue repair, in comparison to the histopathological and proliferative changes in a rat model of methotrexate-induced small intestinal mucositis. Histological analysis of the intestinal specimens revealed crypt loss and villus atrophy with damage maximal on day 5 after methotrexate injection, and normalization of mucosal structure commencing on day 6. Crypt cell proliferation was decreased dramatically on day 3, normalized on day 4 and up-regulated on days 5 and 6. HGF and c-met protein/mRNA expression was up-regulated between days 4 and 7, with the mRNA co-localizing to the crypt and lower villus epithelium. Therefore, following methotrexate injection, a decrease in crypt cell proliferation preceded histological damage, and conversely, crypt cell hyperproliferation preceded mucosal regeneration. Up-regulation of HGF and c-met coincided with crypt hyperproliferation and mucosal recovery, suggesting a role for HGF in intestinal repair following acute injury. The crypt epithelial localization of HGF and c-met implies an autocrine or paracrine mechanism of HGF action. © 2000 Cancer Research Campaign

Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats.

Proliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths of small intestinal crypts in a proximal-to-distal decreasing gradient along the small intestine. The remaining crypt epithelium appeared flattened, except for Paneth cells, in which lysozyme protein and mRNA expression was increased. Regeneration through increased proliferation during days 3-4 coincided with villus atrophy, showing decreased numbers of villus enterocytes and decreased expression of the enterocyte-specific genes sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet cells were spared at villus tips and remained functional, displaying Muc2 and trefoil factor 3 expression. On days 8-10, all parameters had returned to normal in the whole small intestine. No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon. The observed small intestinal sparing of Paneth cells and goblet cells following exposure to methotrexate is likely to contribute to epithelial defense during increased vulnerability of the intestinal epithelium.

Lactoferrin protects gut mucosal integrity during endotoxemia induced by lipopolysaccharide in mice.

The hypothesis that lactoferrin protects mice against lethal effects of bacterial lipopolysaccharide (LPS) is the subject of experimental investigations described in this article. Lipopolysaccharide is a powerful toxin produced by gram negative bacteria that when injected into humans or experimental animals reproduce many of the pathophysiologic and immune responses caused by live bacteria. Lactoferrin administered intraperitoneally 1 hr prior to injection of LPS significantly enhanced the survival of mice, reducing LPS-induced mortality from 83.3% to 16.7%. Changes in locomotor and other behavioral activities resulting from LPS injection were not present in mice treated with lactoferrin. Also, histological examination of intestine revealed remarkable resistance to injury produced by LPS if mice were pretreated with lactoferrin. Severe villus atrophy, edema and epithelial vacuolation were observed in LPS-treated animals but not in lactoferrin-treated counterparts. Electrophysiological parameters were used to assess secretory and absorptive functions in the small intestine. In mice treated with LPS, transmural electrical resistance was reduced and absorption of glucose was increased. Lactoferrin treatment had no significant influence on basal electrophysiological correlates of net ion secretion or glucose absorption nor on changes induced by LPS. Collectively, these results suggest that lactoferrin attenuates the lethal effect of LPS and modulates behavioral and histopathological sequela of endotoxemia.

Food-induced malabsorption syndromes.

A syndrome of chronic diarrhea, vomiting, and failure to thrive was described 35 years ago. The syndrome was caused by damage in the jejunum after ingestion of cow's milk. Symptoms appeared in young infants shortly after introduction of cow's milk formula. Patients had moderate steatorrhea, decreased absorption of D-xylose, and, often, iron-deficiency anemia and hypoproteinemia. They had strong IgA and IgG antibodies to cow's milk. IgE antibodies to cow's milk were negative, as a rule. Indicators of cell-mediated immune reaction to cow's milk proteins were often positive. Patients were tolerant to cow's milk by the age of 3 years. Malabsorption was due to damage to the jejunal mucosa: Varying villus atrophy was associated with inflammation in surface epithelium and lamina propria. The epithelial cell renewal rate increased. Surface epithelial cells decreased in height, with short, furry microvilli and large aggregates of lysozymes. The number of intraepithelial lymphocytes was markedly increased, but normalized during cow's milk elimination. Most of these lymphocytes had alpha/beta T-cell receptors, and many were cytotoxic. Some specimens had an increase in gamma/delta T-cell receptor-bearing cells. In the lamina propria, CD4+ cells predominated, and some of them were activated. IgA- and IgM-containing cells were markedly increased during cow's milk exposure, but IgE cells were not abnormal. The density of eosinophils was moderately increased. Secretion of interferon-gamma by cells isolated from patients' intestines was markedly increased. Morphologic and immunologic findings suggest that T-cell-mediated reaction to proteins in cow's milk is present in the small intestines of patients with this syndrome and causes this enteropathy.

The mammary gland and neonate mucosal immunity

The passive mucosal protection of neonate mammals is dependent on the continuous supply until weaning of maternally dimeric IgA (monogastric) and IgG1 (ruminants). This lactogenic (humoral) immunity is linked to the gut, the so-called entero-mammary link, because of the translocation of Ig (IgA and IgG1) or the emigration of IgA lymphoblasts from the gut into the mammary gland (MG); on the other hand, studies on the lymphocyte subsets in the MG of artiodactyls sustained the view of a true local immune response, depending on the MG stage development. Accordingly, the increase of the lactogenic immunity may focus on (1) inductor sites (gut and, possibly, the MG), (2) increase in cell traffic from the gut into the MG, and (3) enhancement at the effector site of the Ig production and excretion in milk. A specific mucosal environment (interleukins and hormones) is responsible for IgM/IgA switch, the induction of mucosal homing receptor onto lymphoblasts and mucosal vascular addressins; very few data are available for the mechanism of lymphoblasts recruitment, either IgA or IgG1, although lactogenic hormones have been implicated in the IgA-blasts homing into the mice MG. After weaning, the neonate is able to mount a gut immune response, but the shortage of the suckling period did not seem to be detrimental for its onset. In soyabean allergy, both piglet and calf exhibited gut villus atrophy, gut accumulation of IgA (swine) and IgG1 (cattle) immunocytes, sustaining the view that a specific environment in ruminant is responsible for both IgA and IgG1 production.

Temporal changes in TFF3 expression and jejunal morphology during methotrexate-induced damage and repair.

Trefoil factor TFF3 has been implicated in intestinal protection and repair. This study investigated the spatiotemporal relationship between TFF3 expression and morphological changes during intestinal damage and repair in a rat model of methotrexate-induced small intestinal mucositis. Intestinal tissues from rats with mucositis were collected daily for 10 days. Mucosal damage was characterized by an initial decrease in cell proliferation resulting in crypt loss, villus atrophy, and depletion of goblet cells, followed by hyperproliferation that lead to crypt and villus regeneration and mucous cell repopulation. TFF3 mRNA levels increased marginally during histological damage, and the cell population expressing TFF3 mRNA expanded from the usual goblet cells to include some nongoblet epithelial cells before goblet cell repopulation. TFF3 peptide, however, was depleted during histological damage and normalized during repair, mirroring the disappearance and repopulation of goblet cells. Although there is no temporal relationship between TFF3 levels and crypt hyperproliferation, confirming the nonmitogenic nature of TFF3, the coincidental normalization of TFF3 peptide with repopulation of goblet cells and mucin production after proliferative overshoot suggests that TFF3 may play a role in the remodeling phase of repair.

Enhancement of apoptosis with loss of cellular adherence in the villus epithelium of the small intestine after infection with the nematode Nippostrongylus brasiliensis in rats.

It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7-10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.

PBC and the gut: the villi atrophy, the plot thickens

See article on page 736 An association between primary biliary cirrhosis (PBC) and coeliac disease now seems well established. Since the original description by Logan and colleagues,1 there have been...