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Macromolecular Absorption From The Digestive Tract In Young Vertebrates
Published in Károly Baintner, Intestinal Absorption of Macromolecules and Immune Transmission from Mother to Young, 2019
Table 4 is a simplified summary of the hormone dependence of the periclosure enzymatic changes. The same hormone may enhance the activity of some enzymes and suppress others. Glucocorticoids are responsible for most of the changes observed; e.g., for the appearance of sucrase-isomaltase and trehalase. Thyroid hormones play the primary role in the decrease of lactase and in the increase of alkaline phosphatase, and a permissive role in the rise of sucrase547 and in the decrease of lysosomal hydrolases.818 In rat pups made hypothyroid by administration of n-propylthiouracyl, sucrase activity appears at the usual time but rises at a slower rate toward adult levels.546 In vitro enzymic changes of the intestinal tissue resemble the in vivo response.329,689
Gastrointestinal Tract Development and Its Importance in Toxicology
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Alma M. Feldpausch, Joseph V. Rodricks, Rosalind A. Schoof, Brittany A. Weldon
By week 10, a fully differentiated spectrum of endocrine cell types is present in the stomach and duodenum. Sucrase-isomaltase, maltase, and trehalase enzymes are present in the small intestine at 60%–70% of adult levels. Substance P and neurokinin A can be detected in the stomach also at week 10. The gut epithelial barrier develops tight intercellular junctions beginning at week 10, contributing largely to immune function (Maheshwari and Zemlin, 2006). Intestinal epithelial cells also have significant immune functions, including expression of HLA-I and HLA-DR, acting as non-professional antigen-presenting cells (and transferring antigen to lymphoid follicles and Peyer’s patches below), and exhibiting receptors to facilitate immunoglobulin transport.
Fetal and Postnatal Development of the Small and Large Intestine
Published in Jean Morisset, Travis E. Solomon, Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
Ménard Daniel, Calvert Raymond
Thyroxine (T4) may, however, play a role in the modulation of jejunal lactase activity since its administration to hypophysectomized suckling rats restores the normal developmental pattern of lactase.8 This hormonal effect cannot be secondary to glucocorticoid secretion since the circulating concentrations of corticosterone are unaffected by T4 in these hypophysectomized animals. The possibility, however, that the thyroxine effect on lactase activity may result from an altered rate of cellular proliferation and migration must be kept in mind. Indeed, thyroxine treatment is able to increase intestinal cell proliferation and there is evidence that the regulation of lactase expression takes place in two stages during neonatal development, involving reduced lactase synthesis and increased enterocyte replacement.58 The fact that trehalase activity is unaffected by thyroxine treatment in suckling mice59 suggests that thyroxine may have a more limited action, compared to glucocorticoids, on disaccharidase development.
Batten disease: an expert update on agents in preclinical and clinical trials
Published in Expert Opinion on Investigational Drugs, 2020
Margaux C. Masten, Jonathan W. Mink, Erika F. Augustine
Trehalose is a disaccharide composed of two glucose molecules. Studies have shown that trehalose, an activator of Transcription-Factor EB (TFEB), reduces the buildup of lipofuscin in both cell and mouse models [6]. The enzyme trehalase lyses trehalose in the small intestine, so one barrier to using trehalose therapeutically is that it cannot be administered enterally. Pre-clinical studies are being conducted to evaluate intravenous delivery of trehalose along with oral delivery of miglustat which inhibits trehalase [7]. Beyond Batten Disease Foundation (https://beyondbatten.org/research/bbdf101/, 7/12/2020) and Theranexus Inc (https://www.theranexus.com/en/platform-and-products/drug-candidates.html, 7/12/2020) have partnered to develop a clinical trial of trehalose in combination with miglustat (BBDF-101) for CLN3 disease.
Microbial and metabolic impacts of trehalose and trehalose analogues
Published in Gut Microbes, 2020
Yiming Zhang, Brian J. DeBosch
Exemplifying key distinctions between trehalose and LT at the gene-specific level, trehalose induced antioxidant genes40-42 topoisomerase 2b (Top2b) and thioredoxin reductase (Txnrd1), to a greater extent than LT (Figure 2(d)). By comparison, LT uniquely induced lipocalin (Lcn2) and lipoic acid synthetase (Lias), each of these which is important in the hepatoprotective anti-oxidant response, and each of which is uniquely regulated by trehalose and LT.43-45 Moreover, we demonstrated previously that LT more potently induces canonical trehalose effectors, hepatocyte Pgc1α, Fgf21, 46Aloxe3 and Arg2.34,47 Differential transcriptomic responses highlight divergent metabolic effects of each disaccharide. This opposes a model in which LT acts as a higher-amplitude trehalose-mimetic stimulus. Therefore, to ascribe the mechanistic differences between these analogues solely to differences in their trehalase susceptibility and bioavailability is probably too simplistic.
Trehalose attenuates spinal cord injury through the regulation of oxidative stress, inflammation and GFAP expression in rats
Published in The Journal of Spinal Cord Medicine, 2019
Mahdieh Nazari-Robati, Mahboobe Akbari, Mohammad Khaksari, Moghaddameh Mirzaee
There are some limitations associated with this study. First, the concentration and dosage of trehalose were used according to previous studies. Therefore, the most appropriate concentration and dosage should be determined. Second, this study was conducted in the early time course following SCI and a single injection of trehalose was used. Thus, delayed biochemical and behavioral assessment as well as multiple injections of trehalose are suggested. Third, intrathecal injection of trehalose is considered as a barrier to its clinical application. In addition, the presence of trehalase limits its oral administration. Therefore, the study of peritoneal injection of trehalose is recommended. Fourth, in the present investigation, the efficacy of trehalose was not compared with other therapeutic agents. Thus, providing comparison is proposed in future clinical studies.