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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.
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PMID:Effect of perfusion rate on absorption, surface area, unstirred water layer thickness, permeability, and intraluminal pressure in the rat ileum in vivo. 113 32

Maintaining rats on total parenteral nutrition (TPN) for 6 days significantly reduced mass (-34%), protein (-32%), and DNA (-35%) in small intestine and colon (29-37% decrease). Coinfusion of glucagon-like peptide-2 (GLP-2) normalized each of these variables in duodenum, jejunum, and ileum, but not in colon. Histological analysis of tissue revealed normal mucosa thickness and villus height in small intestine of GLP-2-treated rats, whereas nontreated rats maintained on TPN exhibited villus shortening (-30%) and thinning (-23%) of mucosa. These results suggest that hormonal alterations may be more important than an absence of luminal nutrition in TPN-associated mucosal changes. Additionally, GLP-2 normalization of gut mucosa permits accurate assessment of the influence of reversal of hypoplasia on gut barrier function.
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PMID:Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of glucagon-like peptide-2. 927 38

Asthma guidelines recommend the use of inhaled glucocorticoids (GCS). However, high doses increase the risk of systemic effects including suppression of the hypothalamic-pituitary-adrenal (HPA) axis by negative feedback, reduction of bone mass, inhibition of growth in children and skin thinning. Plasma concentration depends on the dose delivered from the inhaler, the distribution of delivery (ratio of lung to gut), and the degree of first-pass metabolism. Improving lung delivery increases lung absorption and reduces gut absorption and, depending on the extent of first-pass metabolism, may have significant effects on the systemic drug load. Qvar (3M Pharmaceuticals' hydrofluoroalkane beclomethasone dipropionate (HFA-BDP)), which produces an extra fine aerosol, improves lung delivery without producing clinically significant HPA suppression within the recommended dose range. Within this range Qvar produces no more HPA suppression than an equal dose of CFC-BDP and, in addition, lower doses of Qvar are effective in asthma control.
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PMID:Steroid safety: the endocrinologist's view. 1034 32

Patterning of the gut into morphologically distinct regions results from the appropriate factors being expressed in strict spatial and temporal patterns to assign cells their fates in development. Often, the boundaries of gene expression early in development correspond to delineations between different regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard. Ectopic BMP4 in the gizzard caused a thinning of the muscularis. To understand this phenotype we examined the expression of the receptors transducing BMP signaling during gut development. We find that the BMP receptors are differentially expressed in distinct regions of the chicken embryonic gut. By using constitutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expressed. We show that the mesodermal thinning seen upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in proliferation within the gizzard mesoderm. The mesodermal thinning is characterized by a disorganization and lack of differentiation of smooth muscle in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4. This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard. We also find that Nkx2.5 is necessary and sufficient for establishing aspects of pyloric sphincter differentiation.
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PMID:Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary. 1093 12

Maintaining tumor-bearing rats on total parenteral nutrition (TPN) for eight days significantly reduced mass, protein, and DNA in small intestine and colon. Coinfusion of glucagon-like peptide 2 (GLP-2) significantly increased each of these variables in the duodenum, jejunum, and ileum, but not in the colon. Histological analysis of tissue revealed normal mucosa thickness and villus height in the small intestine of GLP-2-treated rats, whereas non-treated rats maintained on TPN exhibited villus shortening and thinning of the mucosa. Compared with TPN alone, no significant effects of GLP-2 were noted on tumor growth, liver weight, or heart weight. Coinfusion of GLP-2 with TPN had no significant effect on TPN-associated immunosuppression, as measured by mitogen-induced proliferation of cultured splenocytes. Although translocation of bacteria to the mesenteric lymph nodes appeared to be reduced in GLP-2-treated rats, the difference between groups was not statistically significant. These results suggest that hormonal alterations may be more important than an absence of luminal nutrition in TPN-associated mucosa changes in tumor-bearing rats. Additionally, maintenance of gut integrity during TPN does not appear to be a sufficient condition for the avoidance of the negative sequelae associated with this route of supplemental nutrition.
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PMID:Maintaining gut integrity during parenteral nutrition of tumor-bearing rats: effects of glucagon-like peptide 2. 1114 96

The involvement of intestinal damage in experimental African trypanosomiasis was investigated in rats infected with Trypanosoma brucei brucei by measuring the urinary excretion of the previously administered non-metabolizable sugar probes, D-mannitol and lactulose, and the flux of FITC-dextran across isolated, everted gut segments. There was increased urinary recovery and flux of the sugar probes across the intestine which were significant (P < 0.05) and maximum at day 21 of the infection, but subsequently reduced, in the terminal stages of infection (day 33 p.i.). In the case of the everted sac studies the reductions were to less than 25% control values (P < 0.001). Levels of circulating endotoxin were increased approximately 3-fold at day 21 p.i., 4-fold at day 33 p.i., compared to controls. At day 21 there was a significant correlation (r = 0.63, P < 0.01) between the log endotoxin levels and the increased sugar excretion expressed as the lactulose/mannitol ratios. Histological studies showed damage to the villi, wall thinning and marked cellular infiltrations, which were very prominent in the proximal jejunum and duodenum. These results demonstrate that during trypanosome infections in rats, increased intestinal leakage and increased circulating endotoxins are significant pathological features.
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PMID:The relationships between intestinal damage and circulating endotoxins in experimental Trypanosoma brucei brucei infections. 1211 14

Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1microg/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.
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PMID:Insulin-like growth factor-I governs submucosal growth and thickness in the newborn mouse ileum. 1468 93

The digesta in four gut compartments (proximal and distal halves of small intestine, caecum, and proximal colon) of a wild hindgut fermenting herbivore, the common brushtail possum (Trichosurus vulpecula), were investigated by rheometry and permeametry. Digesta from all compartments were highly viscous and exhibited shear-thinning. Apparent viscosity was positively related to dry matter content, and increased from proximal small intestine to colon. Dynamic rheological measurements showed that in small intestinal digesta the elastic modulus was greater than the viscous modulus and their ratios were characteristic of weak gels, indicating that digesta could sustain compression. The apparent viscosity of distal small intestinal digesta was markedly lower when measured by capillary viscometry than by rotatory viscometry, indicating that plug flow was likely to be facilitated by lubrication from a peripheral layer of less viscous fluid; i.e., there was an augmented plug flow. Permeametry showed that fluid was extruded from all digesta on compression at physiological pressures, that there was significant permeability of proximal and distal small intestinal digesta, but that digesta became progressively compacted during permeation, with a concomitant reduction in permeability as dry matter content increased. It is proposed that conditions within the small intestine differ from those of an ideal plug flow reactor as radial mixing and turbulence cannot occur. Instead, we suggest that segmentation and peristalsis aid radial mixing of the fluid phase by compressing the solid phase, with extrusion of fluid through the digesta plug. This extrusion may be followed by resorption of fluid back into the plug when the elasticity of the solid phase of digesta is Hookean, thus aiding the mixing of secreted enzymes with insoluble substrates within the plug.
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PMID:Periodic fluid extrusion and models of digesta mixing in the intestine of a herbivore, the common brushtail possum (Trichosurus vulpecula). 1592 16

During the past decade, a detailed understanding has emerged of the aminergic and peptidergic neural pathways present within the brain that regulate appetite. Central among the peptide regulators is neuropeptide Y (NPY), a potent orexigenic agent that acts through five different receptor subtypes. Efforts to find novel appetite suppressant drugs that inhibit the interaction of NPY with either the NPY Y1 or NPY Y5 receptor subtypes have proven disappointing. Attempts have now been made to identify an NPY Y2 stimulator that will suppress appetite. Within the hypothalamus, NPY Y2 receptors have a predominantly presynaptic location where they act to inhibit NPY release. Stimulation of NPY Y2 receptors with synthetic peptide ligands or the gut derived peptide PY3-36 has been shown to reduce food intake. The NPY Y2 receptor has a wide distribution both within the brain and in the periphery. Stimulation of the NPY Y2 subtype at these sites produces a wide array of effects unrelated to changes in food intake. In consequence, the administration of both endogenous and exogenous agonists of the NPY Y2 receptor is likely to cause side effects, particularly regarding pituitary hormone release, as well as on the cardiovascular and gastrointestinal systems. The possibility that long-term NPY Y2 agonism could cause bone thinning and retinal angiogenesis are of particular concern and will need to be investigated as drug discovery moves forward.
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PMID:Neuropeptide Y2 receptors as drug targets for the central regulation of body weight. 1625 21

The initial opening between the gut and the outside of the deuterostome embryo breaks through at the extreme anterior. This region is unique in that ectoderm and endoderm are directly juxtaposed, without intervening mesoderm. This opening has been called the stomodeum, buccopharyngeal membrane or oral cavity at various stages of its formation, however, in order to clarify its function, we have termed this the "primary mouth". In vertebrates, the neural crest grows around the primary mouth to form the face and a "secondary mouth" forms. The primary mouth then becomes the pharyngeal opening. In order to establish a molecular understanding of primary mouth formation, we have begun to examine this process during Xenopus laevis development. An early step during this process occurs at tailbud and involves dissolution of the basement membrane between the ectoderm and endoderm. This is followed by ectodermal invagination to create the stomodeum. A subsequent step involves localized cell death in the ectoderm, which may lead to ectodermal thinning. Subsequently, ectoderm and endoderm apparently intercalate to generate one to two cell layers. The final step is perforation, where (after hatching) the primary mouth opens. Fate mapping has defined the ectodermal and endodermal regions that will form the primary mouth. Extirpations and transplants of these and adjacent regions indicate that, at tailbud, the oral ectoderm is not specifically required for primary mouth formation. In contrast, underlying endoderm and surrounding regions are crucial, presumably sources of necessary signals. This study indicates the complexity of primary mouth formation, and lays the groundwork for future molecular analyses of this important structure.
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PMID:Development of the primary mouth in Xenopus laevis. 1667 48


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