Gastrointestinal Function and Toxicology in Canines
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Each intestinal villus is almost finger-like in shape and if a cross-section is transversely cut at mid level through a villus, it would appear somewhat like a small onion. The outermost layer would be the brush border, as discussed previously. Immediately deep to this would be the enterocytes themselves firmly anchored to the deeply underlying basement membrane. The inner area of each villus is a network of vasculature embedded in loose connective tissue. Capillaries connect a supplying artery with a draining vein. At the innermost central core is the very important central lacteal, which is located approximately along the central axis of each villus and collects the lymphatic fluid draining the villus. The lymphatic system is an accessory route by which fluid can flow from interstitial areas eventually back into the blood. However, the lymphatic fluid can also carry whole proteins, large molecules, fat and particulate matter away from a local tissue space eventually back into the blood. This alternative route compensates for the fact that none of these materials can be directly absorbed into the bloodstream.
Glucagon-Like Peptide-2 in Short Bowel Syndrome
John K. DiBaise, Carol Rees Parrish, Jon S. Thompson in Short Bowel Syndrome Practical Approach to Management, 2017
In a phase I trial, subcutaneous teduglutide injection at doses ranging from 2.5 to 10 mg were shown to be safe and well tolerated in healthy volunteers [6]. Peak plasma concentrations were achieved 3 hours after injection. In 2001, an open-label study with native GLP-2 was completed in eight SBS patients without a colon [7]. These included four patients receiving PN (mean length of residual jejunum, 83 cm) and four patients not receiving PN (mean length of residual jejunum, 106 cm) [7]. All had SBS for more than 1 year (range, 4–17 years) and were considered to be in a stable phase. The mean small intestine length was 83 cm (range, 65–170 cm). None of the six patients with Crohn’s disease had signs of active disease. Four hundred micrograms of subcutaneous GLP-2 was administered twice daily for a total of 35 days. A significant increase in fluid absorption was reported; however, significant increases in total energy, electrolyte, carbohydrate, protein, and fat absorption were not observed. Subject body weight increased by a mean of 1.2 kg. A significant increase in intestinal villus height and crypt depth was observed, supporting a trophic effect of GLP-2 in humans. Furthermore, GLP-2 was well tolerated by all the subjects and side effects were minimal, including erythema and tenderness at the injection site. This study concluded that GLP-2 exhibits its clinical benefit primarily by increasing fluid absorption.
Macromolecular Absorption From The Digestive Tract In Young Vertebrates
Károly Baintner in Intestinal Absorption of Macromolecules and Immune Transmission from Mother to Young, 2019
Receptors were demonstrated primarily on the apical half1019 or on the apical and middle thirds of intestinal villi,1213 but they were lacking in the basic third of the villi, in the Lieberkühn crypts, and in the goblet cells.1213 In the enterocyte the receptor is found in coated vesicles (see Section C below) and in the plasma membrane, mainly in the brush border,651, 1534 but also in the basolateral membrane.2,1213,1571,1575 On the latter site, receptors may occur that have crossed the cell and released the IgG on the basolateral side. Another possibility is the lateral diffusion of the receptor417 from the brush border to the basolateral membrane. In vivo this may be prevented by the tight junctions.1150’1634 and in vitro it may be delayed by low temperature. In the plasma membrane the receptor seems to be localized in outward orientation, accessible for added immunoglobulins.
Short-term use of ceftriaxone sodium leads to intestinal barrier disruption and ultrastructural changes of kidney in SD rats
Published in Renal Failure, 2023
Wenli Zou, Yueming Liu, Wei Zhang, Bo Lin, Wei Shen, Yiwen Li, Qiang He, Juan Jin
To evaluate intestinal barrier function, we examined the initial segment of the colon mucosa using TEM and measured intestinal villus length. At high magnification, tight junctions between epithelial cells showed normal morphology in all the colon sections in all groups. the rats of the CON and TAK groups, the surface microvilli of the mucosal epithelium of rat colon were uniform in size and showed a neat arrangement (Figure 6A and C). Dramatic morphological changes in the colon were observed in rats in the Cef group, where the microvilli were misaligned, and morphologically intact bacteria were observed on the epithelial cell surface (Figure 6B). These results indicate that epithelial junction integrity was not compromised after short-term antibiotic treatment. Compared with the CON and TAK groups, the villus in the CEF group was significantly shortened (Figure 1D).
Gut microbiota: what is its place in pharmacology?
Published in Expert Review of Clinical Pharmacology, 2019
Aleksandra Tarasiuk, Jakub Fichna
In the stomach, which is lined with a single layer of squamous epithelium, its cells are responsible for the secretion of hydrochloric acid, digestive enzymes, and mucus. In the small intestine, a thick type of epithelium is present – single-layer cubic or columnar, constituting a natural protective barrier. It performs both secretory and transport functions, related to the absorption of many substances. The epithelial surface in the small intestine is characterized by the presence of numerous cavities and folds, formed by glands, crypts, and villi, which is an expression of the adaptation of this part of the GI tract to the function performed. The epithelium of the intestinal villi consists of capillary epithelial cells. It is formed by single tentacles, so-called microvilli that also increase its surface. Under the epithelium of the villi, in the middle of the lamina propria, a network of lymph vessels is located. Enterocytes are alternated with intestinal goblet cells secreting mucus. The core of the intestinal villi consists of cylindrical, straight cavities that extend to the muscular layer but are not penetrating. At the bottom of the crypts there are stem cells, and above them, Paneth cells, secreting antibacterial lysozyme. The epithelium located above the lymphoid cells of the intestine, in which Peyer’s patches are present, is a characteristic area of the intestine due to the microcavities and microfold cells located there. The main role of these cells is both the recovery of shortened or irregular villi or pits, as well as the transport of microorganisms from the intestinal lumen to deeper epithelial layers.
Small but powerful: will nanoparticles be the future state‐of‐the‐art therapy for IBD?
Published in Expert Opinion on Drug Delivery, 2022
Kristina Lechner, Mahira Zeeshan, Maxi Noack, Hussain Ali, Markus F. Neurath, Benno Weigmann
The acidic environment and presence of enzymes in the stomach makes this organ infeasible for drug absorption. The intestinal epithelium with its various types of cells and structures, is more absorptive. The epithelium constituting intestinal villi and crypts consists of enterocytes, which can passage molecules butnot pathogens and goblet cells, which secrete mucus . In addition, M cells, located within the epithelium of Peyer<apos;>s patches, are composed of enterocytes and a few goblet cells which provide an environment for nanoparticle uptake processes [86]. These cells are connected by tight junctions, composed of claudins, occludins and junction adhesion molecules forming a strong barrier that hinders the passage of molecules and pathogens [87]. Intestinal permeability may be modified by IBD, especially in UC, allowing nanoparticles to be more easily transported through the intestinal epithelial barrier [88]. Transcellular transport of nanoparticles involves transcytosis, in which particles are taken up by cells. This begins with an endocytic process that occurs at the cell apical membrane. Subsequently, nanoparticles are transported through the cells and released at the basolateral pole, where they may interact with immune cells in the submucosal layer. However, the transport of nanoparticles via this route depends on the physiology of the GI tract. Likewise, such transport studies need more exploration because these experiments are performed only in animal models [76].
Related Knowledge Centers
- Basement Membrane
- Circular Folds
- Enterocyte
- Epithelium
- Gastrointestinal Tract
- Microvillus
- Amino Acid
- Small Intestine
- Lumen
- Brush Border