IMAGING DIAGNOSIS-MUSCULAR HYPERTROPHY OF THE SMALL INTESTINE AND PSEUDODIVERTICULA IN A HORSE.

A 14-year-old Thoroughbred gelding was presented for chronic colic and weight loss. Transcutaneous and transrectal abdominal ultrasonography revealed distended, thickened small intestine with primary thickening of the muscularis and a focally more thickened loop with an echoic structure crossing the wall from the mucosa to the serosa. Visualization of diffuse thickening of the muscularis (muscular hypertrophy of the small intestine) and a focal lesion (pseudodiverticulum) helped clinicians make informed decisions. This case illustrates the importance of transabdominal and transrectal ultrasonography in horses with chronic colic and the relevance of considering the abnormalities in layering pattern of the intestinal wall.

Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine

Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.

Cholesteryl ester accumulation and accelerated cholesterol absorption in intestine-specific hormone sensitive lipase-null mice

Hormone sensitive lipase (HSL) regulates the hydrolysis of acylglycerols and cholesteryl esters (CE) in various cells and organs, including enterocytes of the small intestine. The physiological role of this enzyme in enterocytes, however, stayed elusive. In the present study we generated mice lacking HSL exclusively in the small intestine (HSLiKO) to investigate the impact of HSL deficiency on intestinal lipid metabolism and the consequences on whole body lipid homeostasis. Chow diet-fed HSLiKO mice showed unchanged plasma lipid concentrations. In addition, feeding with high fat/high cholesterol (HF/HC) diet led to unaltered triglyceride but increased plasma cholesterol concentrations and CE accumulation in the small intestine. The same effect was observed after an acute cholesterol load. Gavaging of radioactively labeled cholesterol resulted in increased abundance of radioactivity in plasma, liver and small intestine of HSLiKO mice 4h post-gavaging. However, cholesterol absorption determined by the fecal dual-isotope ratio method revealed no significant difference, suggesting that HSLiKO mice take up the same amount of cholesterol but in an accelerated manner. mRNA expression levels of genes involved in intestinal cholesterol transport and esterification were unchanged but we observed downregulation of HMG-CoA reductase and synthase and consequently less intestinal cholesterol biosynthesis. Taken together our study demonstrates that the lack of intestinal HSL leads to CE accumulation in the small intestine, accelerated cholesterol absorption and decreased cholesterol biosynthesis, indicating that HSL plays an important role in intestinal cholesterol homeostasis.

Evidence of native starch degradation with human small intestinal maltase-glucoamylase (recombinant)

Action of human small intestinal brush border carbohydrate digesting enzymes is thought to involve only final hydrolysis reactions of oligosaccharides to monosaccharides. In vitro starch digestibility assays use fungal amyloglucosidase to provide this function. In this study, recombinant N-terminal subunit enzyme of human small intestinal maltase-glucoamylase (rhMGAM-N) was used to explore digestion of native starches from different botanical sources. The susceptibilities to enzyme hydrolysis varied among the starches. The rate and extent of hydrolysis of amylomaize-5 and amylomaize-7 into glucose were greater than for other starches. Such was not observed with fungal amyloglucosidase or pancreatic alpha-amylase. The degradation of native starch granules showed a surface furrowed pattern in random, radial, or tree-like arrangements that differed substantially from the erosion patterns of amyloglucosidase or alpha-amylase. The evidence of raw starch granule degradation with rhMGAM-N indicates that pancreatic alpha-amylase hydrolysis is not a requirement for native starch digestion in the human small intestine.

Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease

Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium.

A stereological comparison of villous and microvillous surfaces in small intestines of frugivorous and entomophagous bats: species, inter-individual and craniocaudal differences

The extents of functional surfaces (villi, microvilli) have been estimated at different longitudinal sites, and in the entire small intestine, for three species of bats belonging to two feeding groups: insect- and fruit-eaters. In all species, surface areas and other structural quantities tended to be greatest at more cranial sites and to decline caudally. The entomophagous bat (Miniopterus inflatus) had a mean body mass (coefficient of variation) of 8.9 g (5%) and a mean intestinal length of 20 cm (6%). The surface area of the basic intestinal tube (primary mucosa) was 9.1 cm2 (10%) but this was amplified to 48 cm2 (13%) by villi and to 0.13 m2 (20%) by microvilli. The total number of microvilli per intestine was 4 x 10(11) (20%). The average microvillus had a diameter of 8 nm (10%), a length of 1.1 microns (22%) and a membrane surface area of 0.32 micron 2 (31%). In two species of fruit bats (Epomophorus wahlbergi and Lisonycteris angolensis), body masses were greater and intestines longer, the values being 76.0 g (18%) and 76.9 g (4%), and 73 cm (16%) and 72 cm (7%), respectively. Surface areas were also greater, amounting to 76 cm2 (26%) and 45 cm2 (8%) for the primary mucosa, 547 cm2 (29%) and 314 cm2 (16%) for villi and 2.7 m2 (23%) and 1.5 m2 (18%) for microvilli. An increase in the number of microvilli, 33 x 10(11) (19%) and 15 x 10(11) (24%) per intestine, contributed to the more extensive surface area but there were concomitant changes in the dimensions of microvilli. Mean diameters were 94 nm (8%) and 111 nm (4%), and mean lengths were 2.8 microns (12%) and 2.9 microns (10%), respectively. Thus, an increase in the surface area of the average microvillus to 0.83 micron 2 (12%) and 1.02 microns 2 (11%) also contributed to the greater total surface area of microvilli. The lifestyle-related differences in total microvillous surface areas persisted when structural quantities were normalised for the differences in body masses. The values for total microvillous surface area were 148 cm2g-1 (20%) in the entomophagous bat, 355 cm2g-1 (20%) in E. wahlbergi and 192 cm2g-1 (17%) in L. angolensis. This was true despite the fact that the insecteater possessed a greater length of intestine per unit of body mass: 22 mm g-1 (8%) versus 9-10 mm g-1 (9-10%) for the fruit-eaters.

Efficient and Safe Small-Bowel Adhesiolysis

Small-intestine adhesiolysis can be very time consuming and may be associated with bowel wall damage. The risk for injuries to the small or large bowel resulting in increased morbidity and costs is considerable. Both efficient and gentle dissection of adhesions is important in order to avoid intraoperative perforation or, worse, postoperative intestinal leaks. We present a technique using drops of body-warm isotonic saline solution to create an edematous swelling of the adhesions. This procedure not only protects the bowel from cooling and drying, but also simplifies the dissection and, thus, lowers the risk of intestinal lesions.

Binding studies on isolated porcine small intestinal mucosa and in vitro toxicity studies reveal lack of effect of C. perfringens beta-toxin on the porcine intestinal epithelium

Beta-toxin (CPB) is the essential virulence factor of C. perfringens type C causing necrotizing enteritis (NE) in different hosts. Using a pig infection model, we showed that CPB targets small intestinal endothelial cells. Its effect on the porcine intestinal epithelium, however, could not be adequately investigated by this approach. Using porcine neonatal jejunal explants and cryosections, we performed in situ binding studies with CPB. We confirmed binding of CPB to endothelial but could not detect binding to epithelial cells. In contrast, the intact epithelial layer inhibited CPB penetration into deeper intestinal layers. CPB failed to induce cytopathic effects in cultured polarized porcine intestinal epithelial cells (IPEC-J2) and primary jejunal epithelial cells. C. perfringens type C culture supernatants were toxic for cell cultures. This, however, was not inhibited by CPB neutralization. Our results show that, in the porcine small intestine, CPB primarily targets endothelial cells and does not bind to epithelial cells. An intact intestinal epithelial layer prevents CPB diffusion into underlying tissue and CPB alone does not cause direct damage to intestinal epithelial cells. Additional factors might be involved in the early epithelial damage which is needed for CPB diffusion towards its endothelial targets in the small intestine.