Changes in the peritoneum of the small intestine and diaphragm in experimental portal hypertension

Diaphragm and small intestine peritoneum morphology was studied in experimental portal hypertension in rats with the help of luminescent, transmission and scanning electron microscopy techniques. Structural organizations of these peritoneum portions and performance function were different: fluid transudation realized through the small intestine peritoneum and resorption occurred via diaphragm peritoneum. Morphological signs allowed to judge about the increasing of fluid transudation in abdominal cavity and diaphragmatic resorption in early period of portal hypertension. Morphological alterations appeared in peritoneum resorption sites (pumping diaphragmatic hatchs) according to progress of portal hypertension that indicated decompensation process of peritoneal fluid absorption and led to ascites.     

Absorption of 241Am in the gastrointestinal tract

In experiments with rats a study was made of a number of factors influencing the resorption of 241Am from the gastrointestinal tract (GIT). The resorption of 241Am from GIT was found to be 120-245 times more intensive in neonatal rats, during the first 21 days after birth (a milk diet), than in adult animals. A milk diet for adult rats produced a 5-fold increase in the resorption of 241Am from GIT. The additional administration of digestive enzymes, as a homogenate from pancreas and small intestine, produced a 7--9-fold increase in the rate of 241Am resorption from GIT.     

Integrating miRNA and mRNA expression profiles in response to heat stress-induced injury in rat small intestine

The molecular mechanisms underlying the pathophysiology of heat stress in the small intestine remain undefined. Furthermore, little information is available concerning changes in microRNA (miRNA) expression following heat stress. The present study sought to evaluate miRNA and mRNA expression profiles in the rat small intestine in response to heat stress. Male Sprague-Dawley rats were subjected to 2?h of heat stress daily for ten consecutive days. Rats were sacrificed at specific time points immediately following heat treatment, and morphological changes in the small intestine were determined. The miRNA and mRNA expression profiles from sample of small intestine were evaluated by microarray analysis. Heat stress caused pronounced morphological damage in the rat small intestine, most severe within the jejunum after 3?days of heat treatment. A mRNA microarray analysis found 270 genes to be up-regulated and 122 genes down-regulated (P?≤?0.01, ≥2.0-fold change) in the jejunum after heat treatment. A miRNA microarray analysis found 18 miRNAs to be up-regulated and 11 down-regulated in the jejunum after heat treatment (P?≤?0.05). Subsequent bioinformatic analyses of the differentially expressed mRNAs and miRNAs were carried out to integrate miRNA and mRNA expression and revealed that alterations in mRNA following heat stress were negatively correlated with miRNA expression. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of heat stress-induced injury in the small intestine, specifically with regard to miRNAs.     

Surgical stress-induced alterations in retinoid metabolism in the small intestine: role of oxygen free radicals

Oxidative stress in the small intestine can result in altered cell proliferation, migration, and differentiation of villus-crypt cells. Retinoid metabolism is recognized as an important mediator of cellular differentiation in the intestine. This study examined the effect of oxidative stress in retinoid metabolism in a surgical stress model. Surgical stress was performed by handling the intestine as done during laparotomy. Villus-crypt cells were isolated at different time periods and various retinoid concentrations in the cell homogenate and the retinoic acid forming enzymes were quantitated using HPLC. Surgical stress resulted in altered retinoid levels in various cell populations in the small intestine at 1 and 12h. The activity of alkaline phosphatase and retinal oxidase was also altered at these time points and all these changes were prevented by inhibiting superoxide generation using xanthine oxidase inhibitor, allopurinol. These studies suggest that alterations seen in enterocytes during surgical stress may be mediated by changes in retinoid metabolism.     

Decrease in muscarinic acetylcholine receptors in the small intestine of mice subjected to repeated cold stress

The maximal contraction of the small intestine by acetylcholine greatly decreased during repeated cold stress. This change was mainly due to decrease in muscarinic receptors in small intestine, whose amounts were measured by the binding of 3-quinuclidinyl benzilate. Injection of norepinephrine or a tricyclic antidepressant, carpipramine during the exposure to the stress prevented this decrease in muscarinic receptors. The physiological significance of this phenomenon is discussed in relation to vagal hyperactivity under the stress.     

Effect of bovine small intestine thioredoxin on aldose reductase activity

Under oxidative stress mediated by H(2)O(2), significant activation of purified aldose reductase from bovine small intestine was observed in the presence of purified thioredoxin from bovine small intestine.     

Effect of bovine small intestine thioredoxin on aldose reductase activity

Under oxidative stress mediated by H₂O₂, significant activation of purified aldose reductase from bovine small intestine was observed in the presence of purified thioredoxin from bovine small intestine.     

Periodic fluid extrusion and models of digesta mixing in the intestine of a herbivore,the common brushtail possum (<Emphasis Type="Italic">Trichosurus vulpecula</Emphasis>)

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.     

Transient changes of enzyme activities and expression of stress proteins in the small intestine of piglets after weaning

To determine the transient effects of weaning on the small intestine, 16 piglets were slaughtered at days 0, 1, 4 and 7 after weaning. Jejunal samples were collected to examine different enzyme activities and mRNA expressions of two stress protein families, namely, heat-shock proteins (HSP) and trefoil factors (TFF). Results showed that the activities of ceruloplasmin, alkaline phosphatase and lactate dehydrogenase, were significantly changed at Day 1 and/or Day 4. The mRNA expressions of HSP10, HSP60 and HSP90 showed a pattern of increased expression with time after weaning. Expression significantly differed between Day 0 and Day 7 after weaning. The mRNA expression of HSP70 was significantly increased on Day 1 only. Similarly, the mRNA expressions of TFF1 and TFF2 were significantly increased on Day 7 compared with those on Day 0. Expression of TFF3 was not affected by time after weaning. In conclusion, the present study indicated that weaning induced transient injury to small intestinal morphology and function. Particularly it changed enzyme activities and gene expression of stress proteins in the small intestine of piglets. At first time, a change in the gene expression of HSP10 and a gene overexpression of TFF1 in the small intestine of piglets after weaning was found.     

Microarray analysis of gene expression profiles of rat small intestine in response to heat stress

Ambient temperature is a critical factor that affects biological organisms in many ways. In this study, the authors investigated gene expression changes in rat small intestine in response to heat stress. Male Sprague-Dawley rats were randomly divided into control and heat-stressed groups. Both groups were housed at 25 °C, although the heat-stressed group was also subjected to 40 °C for 2 h each day for 10 successive days. Rats were sacrificed 1, 3, 6, and 10 days after heat treatment, and sections of their small intestine epithelial tissue were excised for morphological examination and microarray analyses. The rat rectal and body surface temperatures and serum cortisol levels were all significantly increased after heat treatment (p < 0.05). The jejuna were significantly damaged by 3 days after heat treatment began. Microarray analysis showed that 422 genes were differentially expressed, of which 290 genes were significantly upregulated and 132 genes were significantly downregulated. Subsequent bioinformatics analyses revealed that the differentially expressed genes were mainly related to stress, immune regulation, and metabolism processes. The bioinformatics analysis of the differentially expressed genes should be beneficial to further investigations on the underlying mechanisms involved in heat stress-induced damage in the small intestine.     

Catecholamine concentration in adrenergic plexuses of the spleen and intestine during cold-induced and emotional stress

Computer analysis and histochemical techniques were used to investigate catecholamine concentration in the adrenergic plexuses of the spleen and small intestine in rats. The concentration was found to increase during both emotional and short-term cold-induced stress. Injection of 10 mg/kg guanethidine i.p. does not counteract cold-induced accumulation of catecholamines in the adrenergic plexuses of the spleen and small intestine. During emotional stress, by contrast, an accumulation of this sort does take place. The mechanisms potentially underlying catecholamine accumulation in the adrenergic plexus of these organisms associated with different types of stress are discussed. Cold-induced stress is thought to produce catecholamine synthesis in the adrenergic nerve endings of the prevertebral ganglia, whereas emotional stress leads to catecholamine uptake by adrenergic terminals from the blood.Institute of Physiology, Academy of Sciences of the Byelorussian SSR, Minsk. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 347–354, May–June, 1990.     

Antiulcerous efficacy of reamberin at the background of the stress ulcerogenic factor action

The effect of reamberin on morphofunctional changes in the small intestine mucous membrane due to stress ulcerogenesis was studied. Normalization of the lipid modifications in the tissue structure, evident of the drug antiulcerous properties, was observed.     

Expression of stress fibers in bullfrog mesothelial cells in response to tension

The relationship between stress fibers and tension in mesothelial cells of the bullfrog small intestine was examined by fluorescence cytochemistry using en face mesothelial cell preparations. In nontreated controls, actin revealed by rhodamine-phalloidin staining was localized only along the margins of the mesothelial cells. On the other hand, many stress fibers were formed in the mesothelial cells within 5-7 min after stretching of the intestinal wall in a given direction. The orientation of stress fibers within the cells was coincident with the direction of the tension applied. These cytoplasmic fibers disappeared almost completely from the mesothelial cells within 30 min after the release of tension. According to a difference in the intensity of tension necessary for stress fiber expression, the intestinal mesothelial cells were classified into two groups. Furthermore, cells containing stress fibers in each group showed a rapid increase in number once a given value of tension was applied. The present results indicate that the mesothelial cells of bullfrog small intestine may develop stress fibers to counteract tension exerted on the intestinal wall. Such stress fibers may serve to maintain cellular integrity by strengthening the cellular attachment to subepithelial tissue.     

3d Mechanical properties of the partially obstructed guinea pig small intestine

Background and aimsPartial obstruction of the small intestine results in severe hypertrophy of smooth muscle cells, dilatation and functional denervation. Hypertrophy of the small intestine is associated with alteration of the wall structure and the mechanical properties. The aims of this study were to determine three dimensional material properties of the obstructed small intestine in guinea pigs and to obtain the 3D stress–strain distributions in the small intestinal wall.MethodsPartial obstruction of mid-jejunum was created surgically in five guinea pigs that were euthanized 2 weeks after the surgery. Ten-cm-long segments proximal to the obstruction site were used for the stretch-inflation mechanical test using a tri-axial test machine. The outer diameter, longitudinal force and the luminal pressure during the test were recorded simultaneously. An anisotropic exponential pseudo-strain energy density function was used as the constitutive equation to fit the experimental loading curve and for computation of the stress–strain distribution.ResultsThe wall thickness and the wall area increased significantly in the obstructed jejunum (P<0.001). The pressure—outer radius curves in the obstructed segments were translated to the left of the normal segments, indicating wall stiffening after the obstruction. The circumferential stress and the longitudinal stress through the wall were higher in the obstructed segments (P<0.02). This was independent of whether the zero-stress state or the no-load states were used as the reference state.ConclusionThe mechanical behaviour of the obstructed small intestine can be described using a 3D constitutive model. The obstruction-induced biomechanical properties change was characterized by higher circumferential and longitudinal stresses in the wall and altered material constants in the 3D constitutive model.     

Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function

The aim of this study was to determine the effect of magnesium deficiency on small intestinal morphology and function. Rats were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 weeks. Infiltration of neutrophils and mucosal injury were assessed in stained sections of small intestine. Magnesium deficiency alone induced a significant increase in neutrophil infiltration and increased vascular ICAM-1 expression, in the absence of changes in mucosal injury or expression of proinflammatory mediators. Magnesium deficiency was associated with hyposecretory epithelial cell responses and vascular macromolecular leak in the small intestine and lung, which was attributed partly to reduced expression of NOS-3. To determine the effect of hypomagnesmia on the intestinal responses to a known oxidative stress, groups of rats were randomized to either sham operation or superior mesenteric artery occlusion for 10 (non-injurious) or 30 (injurious) minutes followed by a 1- or 4-hour reperfusion period. In response to mesenteric ischemia/reperfusion, deficient rats showed exaggerated PMN influx, but similar mucosal injury. Intestinal ischemia in sufficient animals induced vascular macromolecular leak in the small intestine and lung at 4 hours of reperfusion, with levels similar to those observed in untreated deficient rats. Acute magnesium repletion of deficient rats 24 h before surgery attenuated the exaggerated inflammation in deficient rats. These data show that magnesium deficiency induced a subclinical inflammation in the small intestine in the absence of mucosal injury, but with significant functional changes in local and remote organs and increased sensitivity to oxidative stress. The opinions contained herein are those of the authors and are not to be construed as official policy or reflecting the views of the Department of Defense     

The Effect of Exogenous Peroxiredoxin 6 on the State of Mesenteric Vessels and the Small Intestine in Ischemia–Reperfusion Injury

Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of ischemia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mesenteric artery, was used in this work. Recombinant peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous peroxiredoxin 6 prior to ischemia–reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric vessels. The impact of the exogenous peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous peroxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normalization of the tissue redox homeostasis, structure protection, and restoration of the microvasculature.     

Genomic and Genetic Characterization of the Bile Stress Response of Probiotic Lactobacillus reuteri ATCC 55730

Probiotic bacteria encounter various stresses after ingestion by the host, including exposure to the low pH in the stomach and bile in the small intestine. The probiotic microorganism Lactobacillus reuteri ATCC 55730 has previously been shown to survive in the human small intestine. To address how L. reuteri can resist bile stress, we performed microarray experiments to determine gene expression changes that occur when the organism is exposed to physiological concentrations of bile. A wide variety of genes that displayed differential expression in the presence of bile indicated that the cells were dealing with several types of stress, including cell envelope stress, protein denaturation, and DNA damage. Mutations in three genes were found to decrease the strain's ability to survive bile exposure: lr1864, a Clp chaperone; lr0085, a gene of unknown function; and lr1516, a putative esterase. Mutations in two genes that form an operon, lr1584 (a multidrug resistance transporter in the major facilitator superfamily) and lr1582 (unknown function), were found to impair the strain's ability to restart growth in the presence of bile. This study provides insight into the possible mechanisms that L. reuteri ATCC 55730 may use to survive and grow in the presence of bile in the small intestine.     

Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase

Prolyl endopeptidases (PEP) (EC 3.4.21.26), a family of serine proteases with the ability to hydrolyze the peptide bond on the carboxyl side of an internal proline residue, are able to degrade immunotoxic peptides responsible for celiac disease (CD), such as a 33-residue gluten peptide (33-mer). Oral administration of PEP has been suggested as a potential therapeutic approach for CD, although delivery of the enzyme to the small intestine requires intrinsic gastric stability or advanced formulation technologies. We have engineered two food-grade Lactobacillus casei strains to deliver PEP in an in vitro model of small intestine environment. One strain secretes PEP into the extracellular medium, whereas the other retains PEP in the intracellular environment. The strain that secretes PEP into the extracellular medium is the most effective to degrade the 33-mer and is resistant to simulated gastrointestinal stress. Our results suggest that in the future, after more studies and clinical trials, an engineered food-grade Lactobacillus strain may be useful as a vector for in situ production of PEP in the upper small intestine of CD patients.