Observation of mucosal pathology after praziquantel treatment in experimental Fibricola seoulensis infection in rats

It is well known that the duodenum of mice or rats infected with Fibricola seoulensis shows atrophy of villi (shortening, blunting, widening, fusion) and hyperplasia of crypts. This study was performed to observe healing process of these pathological changes after deworming with anthelmintic treatment. Albino rats infected each with 1,000 metacercariae of F. seoulensis were treated with single dose of 10 mg/kg praziquantel on day 15 post-infection. On day 1, 3, 5, 7, 15, 21 and 28 after the treatment, they were sacrificed and their duodenums were histopathologically studied. Control (uninfected) rats showed their normal finger-like projections of duodenal villi and well arranged crypts. In comparison, untreated (infected) controls revealed severe mucosal changes characteristic of villous atrophy and crypt hyperplasia in their duodenum. The damaged duodenal mucosa was found to restore its normal morphology after praziquantel treatment; until day 3 post-treatment the mucosa was severely atrophied; on day 5 long and slender villi sometimes appeared among the fused and stout ones; after day 15 the villi were in their normalizing process. From this experiment, it was shown that the mucosal changes in the duodenum of rats caused by F. seoulensis infection were completely reversible in 21-28 days after anthelmintic treatment.     

Chronological observation of intestinal lesions of rats experimentally infected with Echinostoma hortense

Intestinal histopathological changes due to infection with Echinostoma hortense (Trematoda) were studied in rats after experimental infection with the metacercariae. The metacercariae were obtained from the tadpoles of Rana nigromaculata, a second intermediate host infected in the laboratory. Total 18 albino rats (Sprague-Dawley) were given 200 matacercariae each and sacrificed on the day 1, 3, 7, 11, 22 or 44 post-infection (PI). Segments of the small intestine at 1, 3, 5, 8 and 30 cm posterior to the pylorus (PTP) were resected and studied histopathologically. 1. The flukes were seen to have intruded into the intervillous space in the upper small intestine at early stages (1-3 days PI), however, they were located mainly in the intestinal lumen at later stages (7-44 days PI). The flukes were sucking and destroying the epithelial layers of villi with their oral and ventral suckers. 2. Histopathological changes of the intestine were recognizable in as early as 1-3 days after infection, and the changes became severer as the infection progressed. 3. The intestinal mucosa was histopathologically characterized by villous atrophy and crypt hyperplasia throughout the infection period. Major villous changes were blunting, fusion, severe destruction and loss of epithelial layers of villi. Villous/crypt (V/C) height ratio was remarkably reduced from 3:1 in controls to 1:1 in severely infected animals. In the stroma of villi, inflammatory cell infiltrations, vascular congestion, edema, and/or fibrosis were recognized. The goblet cells were increased in number after 11 days PI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of recombinant human interleukin-11 on motilin and substance P release in normal and inflamed rabbits

Recombinant human interleukin-11 (rhIL-11) normalizes depressed smooth muscle tension generation towards motilin and substance P (SP) in rabbits with colitis. The aim of this paper was to evaluate the effect of rhIL-11 treatment on motilin and SP release which could have an effect on the contractility changes. Rabbits received 4, 40, 72 or 720 microg/kg rhIL-11 s.c. or saline, 1 h later a continuous s.c. administration of rhIL-11 was started with or without the induction of colitis (135 mg/kg TNBS) for 5 days. Motilin and SP levels were measured by RIA, motilin mRNA expression by RT-PCR. TNBS-colitis did not affect plasma motilin levels but increased the motilin content of the duodenal mucosa 1.7-fold. rhIL-11 treatment dose-dependently increased plasma motilin levels (720 microg/kg day: 3.5-fold) and the motilin content of the duodenal mucosa (720 microg/kg day: 3.0-fold). The effects of rhIL-11 were similar in normal rabbits and were accompanied by an increased motilin mRNA expression. TNBS-colitis decreased plasma SP levels 2.7-fold and the SP content in the colonic muscle layer 7.1-fold. The decrease in the muscle layer, but not in the plasma, was normalized by rhIL-11 treatment. In normal rabbits, rhIL-11 caused a decrease in plasma SP levels, but had no effect on the tissue content of SP. In conclusion, treatment of inflamed or normal rabbits with rhIL-11 increases plasma and tissue levels of motilin in the duodenal mucosa via an increased expression of motilin in the endocrine cells and induces the release of SP from extrinsic neurons. These changes do not explain the beneficial effect of rhIL-11 on the lowered contractility in inflamed rabbits although a change in balance of neuropeptides may influence gastro-intestinal inflammation.     

FINE STRUCTURE OF CELL SURFACE SPECIALIZATIONS IN THE MATURING DUODENAL MUCOSA OF THE CHICK

Cell surfaces in the duodenal mucosa have been studied in maturing tissue of the chick from incubation until hatching. Changes in the distribution of mitoses in this tissue give an indication of its rate of maturation. This rate is paralleled in developmental changes in microvilli and junctional complexes. Concentration of mitotic figures towards the base of villous folds is gradual from day 9 to day 16, then rapid to day 19, after which the mature pattern is acquired. By day 11, microvilli appear in a regular pattern which does not alter through hatching. Their height remains the same to day 16 when it increases gradually to day 19, then very sharply. The angle formed between the microvilli and the cell surface increases gradually to day 16, giving evidence of advancing internal structure. Changes in cell adhesion also occur at day 16. Thereafter, following trypsin treatment cells are held together in patches by the tight junctions of the terminal bar, although the desmosomes are separated. The timing of these morphological changes is compared with that of alkaline phosphatase accumulation in this tissue as reported by Moog (13). Increase in the surface area of the microvilli parallels the increase in the activity of the enzyme.     

Intestinal histopathology and in situ postures of Gymnophalloides seoi in experimentally infected mice

The intestinal histopathology and in situ postures of Gymnophalloides seoi (Digenea: Gymnophallidae) were studied using C3H/HeN and C57BL/6 mice as experimental hosts; the effects of immunosuppression were also observed. The metacercariae isolated from naturally infected oysters, 300 or 1,000 in number, were infected orally to each mouse, and the mice were killed at days 3-21 post-infection (PI). In immunocompetent (IC) mice, only a small number of flukes were found in the mucosa of the duodenum and jejunum during days 3-7 PI, with their large oral suckers pinching and sucking the root of villi. The intestinal mucosa showed mild villous atrophy, crypt hyperplasia, and inflammations in the villous stroma and crypt, with remarkable goblet cell hyperplasia. These mucosal changes were almost restored after days 14-21 PI. In immunosuppressed (IS) mice, displacement as well as complete loss of villi adjacent to the flukes was frequently encountered, otherwise the histopathology was generally mild, with minimal goblet cell hyperplasia. In these mice, numerous flukes were found, and it seemed that they were actively moving and rotating in situ. Several flukes were found to have invaded into the submucosa, almost facing the serosa. These results indicate that in IC mice the intestinal histopathology caused by G. seoi is generally mild, and the flukes do not penetrate beyond the mucosa, however, in IS mice, the flukes can cause severe destruction of neighboring villi, and some of them invade into the submucosa.     

1,25-Dihydroxyvitamin D3 rapidly alters the morphology of the duodenal mucosa of rachitic chicks: evidence for novel effects of 1,25-dihydroxyvitamin D3

When rachitic chicks are given 1,25-dihydroxyvitamin D3 in amounts as low as 50 ng/bird, the appearance of the duodenal mucosa is altered within 2 h of the administration of the hormone. The changes are most readily apparent on scanning electron microscopy and include: a more plump appearance of villi with loss of furrows and pits on their surfaces, elongation of villi and a smoother, more uniform microvillus surface. These changes occur within 2 h of the administration of the hormone and persist for as long as 24 h. The morphological change precedes the increase in calcium absorption induced by 1,25-dihydroxyvitamin D3 in the intestine. These observations suggest that 1,25-dihydroxyvitamin D3 may play an important part in maintenance of the structure of the duodenal mucosa.     

优势菌群失衡对肠黏膜上皮结构的损害

目的通过观察小鼠肠道优势菌群失衡肠黏膜上皮结构的变化以探讨肠道优势菌群失衡对黏膜机械屏障的影响。方法利用光镜及电镜技术观察轻度、重度菌群失衡小鼠肠道黏膜绒毛形态变化及上皮细胞超微结构的变化。结果菌群失衡小鼠肠黏膜绒毛出现肿胀、断裂,绒毛顶端肠上皮细胞坏死、脱落,重度菌群失衡与轻度菌群失衡小鼠比较绒毛结构受损加重。超微结构观察发现上皮细胞间隙增宽,胞浆内出现空泡结构,黏膜及黏膜下层有淋巴细胞浸润。结论抗生素干扰肠道优势菌群,可导致肠道机械屏障黏膜绒毛及超微结构受损且重度优势菌群失衡的损害大于轻度优势菌群失衡的损害。     

CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes

Gammadelta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gammadelta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCRalphabeta+, and either CD4+ or CD8+, whereas 20% were CD4-CD8- (6 clones) or TCRgammadelta+ (12 clones). A relevant percentage (up to 66%) of TCRgammadelta+ but few (<5%) TCRalphabeta+ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [(3)H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gammadelta T cell clones. Thus, a substantial percentage of TCRgammadelta+ but few TCRalphabeta+ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.     

Morphological and histochemical observations of the regenerated mucosa of the duodenum of the fowl after sub-total villous atrophy

Summary The process of regeneration of the duodenal mucosa of the fowl after subtotal villous atrophy due to coccidiosis infection, was studied. Rapid recovery was shown to occur within twenty four hours of termination of the disease (i.e. day 8 of infection). Extensive hyperplasia was shown in both the newly formed villi and the still elongated crypts. Rapid recovery of all the enzymes and other reactive groups studied was shown in the absorptive cells of the newly formed villi, which had normal and above normal activities. Evidence of a compensatory increase in enzymes and proteins was shown, in particular by the appearance of acid phosphatase, alkaline phosphatase and leucine naphthylamidase activities in the Golgi apparatus as well as an abnormal RNA increase in the upper part of these cells. A possible functional association of the cell organelles can be seen in such hypergenerative cells.     

Atlantic salmon (Salmo salar) protein hydrolysate in diets for weaning piglets ─ effect on growth performance,intestinal morphometry and microbiota composition

Salmon protein hydrolysates (SPH) from two different rest raw materials were evaluated in diets for weaning piglets. Four experimental diets were included in the study: a diet based on plant protein with soy protein as the main protein source (Diet PP), a diet based on fishmeal in exchange for soy protein (Diet FM) and two diets in which different SPH replaced fishmeal in the FM diet. The experimental diets were fed to piglets from the day of weaning until 32 d postweaning. In addition to the record of performance data, an intestinal sampling for mucosal morphometry and microbiota 16S rRNA gene sequencing were performed at day 11 on a subset of the animals. The duodenal villi absorption area was significantly larger in piglets receiving Diets SPH compared with Diet PP (p < 0.02). A significant positive correlation between duodenal villi height and average daily gain during the first 11 d postweaning was detected. Only small differences in intestinal microbiota community and no differences in growth performance were detected between the experimental diets. To conclude, SPH seem to be an interesting novel protein source in weanling piglets.     

The measurement of villus cell population size in the mouse small intestine in normal and abnormal states: a comparison of absolute measurements with morphometric estimators in sectioned immersion-fixed material

From a functional viewpoint, the most important part of the small intestinal mucosa is the villus epithelium; in the experimental study of intestinal adaptation it is often necessary to estimate the size of the population. For these reasons, a systematic study of methods of measuring the size of the villus cell population was undertaken in villi of normal morphology from control animals, and in villi of abnormal morphology as produced by treatment of mice with cytosine arabinoside (Ara-C). The villus cell population can be measured with precision and accuracy in both normal and abnormal mucosal states, with a relative standard error usually less than 5%, with good reproducibility, and with very low counting errors. In the mouse a practically linear relationship between the villus cell population size and position in the small intestine can be shown. In normal, control animals, linear estimates of villus population, for example the villus height, the villus core height, and the villus row count measured in sections of immersion-fixed material, were found to be rough approximations as indicators of the villus cell population, and were highly correlated with it. Product variables, comprising the products of a height with a width measurement, show a large improvement over the linear variables as estimators of villus cell population. In populations of abnormally shaped villi produced by Ara-C, both linear and product variables showed a considerable decrease in correlation with the villus cell population. Consequently, indirect, linear measurements of the villus population size do not accurately reflect the size of the villus population in abnormal villi. Finally, a method comparing theoretical and measured surface: volume indices was used to indicate that the most appropriate shape for normal mouse villi is a simple cylinder; this method would also be applicable for other villus cell populations.     

The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice

The intestinal mast cell response and lymphoblast activity, as measured by the incorporation of 3H-thymidine into mesenteric lymph node cells (MLN) of WBB6F1-w/wv(w/wv) mice, their normal congenic littermates (+/+) and C57BL/6J mice, were compared after infection with Trichinella spiralis. Marked and similar blast cell activity and an increase in number of cells were observed in the MLN of infected w/wv and C57BL/6J mice 7 and 15 days P.I. In contrast to C57BL/6J mice, primary T. spiralis intestinal infections were prolonged in w/wv mice and more muscle larvae were recovered from w/wv mice 29 days post-infection. In C57BL/6J mice mucosal mast cell (MMC) numbers increased on day 7 P.I. whereas in w/wv mice these cells did not increase significantly until day 15 post-infection, reaching a peak on day 22. In w/wv mice, the response to secondary infection as determined by an accelerated expulsion of adult worms did not occur until day 11 postchallenge whereas in +/+ and C57BL/6J mice worm expulsion was nearly complete at that time. In both primary and secondary infections, the MMC numbers in w/wv mice were significantly lower than in C57BL/6J or +/+ mice. The results suggest that prolongation of T. spiralis infection in w/wv mice is associated with delayed appearance of mast cells in the intestinal mucosa which may reflect slow generation of the intestinal inflammatory response.     

The measurement of villus cell population size in the mouse small intestine in normal and abnormal states: a comparison of absolute measurements with morphometric estimators in sectioned immersion-fixed material

Abstract From a functional viewpoint, the most important part of the small intestinal mucosa is the villus epithelium; in the experimental study of intestinal adaptation it is often necessary to estimate the size of the population. For these reasons, a systematic study of methods of measuring the size of the villus cell population was undertaken in villi of normal morphology from control animals, and in villi of abnormal morphology as produced by treatment of mice with cytosine arabinoside (Ara-C).
The villus cell population can be measured with precision and accuracy in both normal and abnormal mucosal states, with a relative standard error usually less than 5%, with good reproducibility, and with very low counting errors. In the mouse a practically linear relationship between the villus cell population size and position in the small intestine can be shown. In normal, control animals, linear estimates of villus population, for example the villus height, the villus core height, and the villus row count measured in sections of immersion-fixed material, were found to be rough approximations as indicators of the villus cell population, and were highly correlated with it. Product variables, comprising the products of a height with a width measurement, show a large improvement over the linear variables as estimators of villus cell population. In populations of abnormally shaped villi produced by Ara-C, both linear and product variables showed a considerable decrease in correlation with the villus cell population. Consequently, indirect, linear measurements of the villus population size do not accurately reflect the size of the villus population in abnormal villi.
Finally, a method comparing theoretical and measured surface: volume indices was used to indicate that the most appropriate shape for normal mouse villi is a simple cylinder; this method would also be applicable for other villus cell populations.     

Angiotensin II type 2 receptor-mediated duodenal mucosal alkaline secretion in the rat

The aims of this study were to elucidate the distribution of angiotensin receptors (AT(1) and AT(2)) in the duodenal wall and to investigate whether AT(2) receptors are involved in the regulation of duodenal mucosal alkaline secretion, which is of importance for the mucosal defense against gastric acid. Immunohistochemistry was used to locate AT(1) and AT(2) receptors in chloralose-anesthetized rats. Duodenal mucosal alkaline output was measured by use of in situ pH-stat titration. Immunohistochemistry demonstrated a distinct staining for both AT(1) and AT(2) receptors in the lamina propria of the villi and also for AT(1) receptors in the muscularis interna. When angiotensin II was infused in the presence of the AT(1) receptor antagonist losartan, mucosal alkaline secretion increased by ~50%. This response was inhibited by the AT(2) receptor antagonist PD-123319. The AT(2) receptor agonist CGP-42112A increased mucosal alkaline secretion by ~50%. This increase was absent in the presence of PD-123319 but not in the presence of losartan or the local anesthetic lidocaine. We conclude that angiotensin II stimulates duodenal mucosal alkaline secretion by activation of AT(2) receptors located in the duodenal mucosa/submucosa.     

Adaptation of intestinal morphology in the temperature-acclimated carp,Cyprinus carpio L.

Summary The effects of temperature and photoperiod acclimation upon the morphology of carp intestinal mucosa have been studied using morphometric techniques. Carp intestine showed an absence of anatomical regionalisation. There was a gradual reduction in the dimensions of villi along the tract. The decrease in the dimensions of the villi was greatest in the anterior half. Temperature acclimation had no effect on intestinal-somatic indices. Acclimation to 10° C or 30° C resulted in large differences in the dimensions of villi. Cold acclimation produced significant increases in mean villus height and breadth along the entire intestine. These villus shape changes resulted in a 58% increase in total mucosal surface area and a 102% increase in total volume of villi in cold-acclimated fish relative to warm-acclimated fish. Surface area of the unmodified intestinal tube increased with cold acclimation by 28%. The total number of villi remained unchanged by thermal acclimation. Because normalisation to a nominal surface area does not take account of the possibility of differentially developed mucosal surfaces in differently acclimated animals, experiments comparing transepithelial transport rates of differently-acclimated fish, using unstripped preparations, overestimates the differences in area-specific transport capacity.     

Experimental candidiasis in Japanese quail: Pathological changes

Candidiasis was experimentally produced in young Japanese quail by oral administration ofCandida albicans cells. Lesions were confined to upper digestive tract with most characteristic changes occurring on the mucosa of crop. No lesions were observed in other tissues of the body. The initial changes in the crop were characterized by thickening and yellowish-white necrotic plaques on the mucosa. From 10th day onwards, there was marked thickening and corrugations of the crop mucosa giving it a typical turkish towel appearance. Varying degree of mucosal swelling was also observed in the oesophagus and proventriculus. Two of the infected birds also revealed yellowish-white necrotic plaques on the tongue at 7th and 10th day post-infection. The prominent microscopic lesions in the crop and tongue consisted of hyperkeratosis and parakeratosis with congestion of the subepithelial tissues. Varying degree of parakeratosis and epithelial hyperplasia coupled with subepithelial oedema and hypertrophy of glands was observed in the oesophagus. The proventriculus and small intestine revealed congestion, oedema, mild to marked goblet cell hyperplasia and focal epithelial sloughing. Fungal elements could be demonstrated in the sections of tongue upto 10 days while in crop upto 14 days post-infection. Reisolation of the fungus was consistently achieved from the crop of infected birds throughout the duration of the experiment.     

Persistent and Compartmentalised Disruption of Dendritic Cell Subpopulations in the Lung following Influenza A Virus Infection

Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung microenvironments in order to regulate tolerance or immunity to inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat of long-term disruption to this balance through its potent pro-inflammatory activities. In this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A Virus infection to examine the effects of IAV on respiratory tissue DC subsets during the recovery phase following clearance of the virus. In adult mice, we found differences in the kinetics and activation states of DC residing in the airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC) compartments. A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b⁺ and CD11b⁻ AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection. In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection. Accompanying this was a change in CD11b⁺and CD11b⁻ PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points. Furthermore, mice infected with IAV at 4 weeks of age showed a significant increase in total numbers of PLDC, and increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days later. These data suggest that the rate of recovery of DC populations following IAV infection differs in the mucosal and parenchymal compartments of the lung and that DC populations can remain disrupted and activated for a prolonged period following viral clearance, into adulthood if infection occurred early in life.     

Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection

Prior studies of intestinal adaptation after massive small bowel resection (SBR) have focused on growth factors and their effects on amplification of the gut mucosa. Because adaptive changes have also been described in intestinal smooth muscle, we sought to determine the effect of targeted smooth muscle growth factor overexpression on resection-induced intestinal adaptation. Male transgenic mice with smooth muscle cell overexpression of insulin-like growth factor I (IGF-I) by virtue of an alpha-smooth muscle actin promoter were obtained. SMP8 IGF-I transgenic (IGF-I TG) and nontransgenic (NT) littermates underwent 50% proximal SBR or sham operation and were then killed after 3 or 28 days. NT mice showed the expected alterations in mucosal adaptive parameters after SBR, such as increased wet weight and villus height. The IGF-I TG mice had inherently taller villi, which did not increase significantly after SBR. In addition, IGF-I TG mice had a 50% postresection persistent increase in remnant intestinal length, which was associated with an early decline and later increase in relative mucosal surface area. These results indicate that growth factor overexpression within the muscularis layer of the bowel wall induces significant postresection adaptive intestinal lengthening and a unique mucosal response. IGF-I signaling within the muscle wall may play an important role in the pathogenesis of resection-induced adaptation.     

Changes of the caecal villi during postnatal development in rats

Summary The villi of the caecal mucosa in postnatal rats were studied using both scanning electron and light microscopy.On the day of birth, numerous villi of various sizes and shapes were present on the caecal mucosa. After the 5th day, the villi decreased very rapidly in length and in number. A strong constriction was observed at the basal region of the caecal villi. During postnatal days 5 9 the villi probably separated and disappeared from the caecal mucosa. No villi were observed in rats that were over 10 days of age.