Time-dependent changes in inhibitory action of lipopolysaccharide on intestinal motility in rat

Endotoxin causes gastrointestinal motility disorder. Aim of this study is to clarify inhibitory mechanisms of lipopolysaccharide (LPS) on smooth muscle contraction in rat ileum. Ileal tissues were isolated from control rat or from LPS-induced peritonitis model rat. Treatment with LPS inhibited carbachol (CCh)-mediated contraction in a time-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes were also upregulated, but iNOS expression was preceded by a rising of COX-2. All subtypes of prostaglandin E₂ (PGE₂) receptors (EP1-EP4) were expressed in ileum, and PGE₂ and selective EP2 or EP4 agonist inhibited CCh-mediated contraction. Selective iNOS inhibitor did not reverse LPS-induced inhibition of contraction by CCh at 1 and 2 hr, but reduced the inhibitory action at 4 hr after the LPS treatment. COX-2 inhibitor reversed the inhibitory action by LPS in all exposure time. Finally, in ileal tissues isolated from peritonitis model rat, iNOS expression was upregulated only at 4 hr after LPS administration, resulting in enhanced inhibitory action of LPS against CCh-induced contraction. In conclusion, LPS induces COX-2 to produce PGE₂, which initially activates EP2 and/or EP4 on smooth muscle cells to inhibit the contractility in early phase of LPS exposure. Moreover, in late phase of LPS treatment, iNOS is expressed to produce NO, which in turn inhibited the contraction by CCh. The inhibitory cascade is similar in the ileum isolated from peritonitis model rat, indicating time-dependent changes of inhibitory action by LPS on intestinal motility in peritonitis.     

Anti-emetic drug maropitant induces intestinal motility disorder but not anti-inflammatory action in mice

Maropitant is a neurokinin 1 receptor (NK1R) antagonist that is clinically used as a new anti-emetic drug for dogs. Substance P (SP) and its receptor NK1R are considered to modulate gastrointestinal peristalsis. In addition, SP works as an inflammatory mediator in gastrointestinal diseases. Aim of this study is to clarify the effects of maropitant on intestinal motility and inflammation in mice. Ex vivo examination of luminal pressure-induced intestinal motility of whole intestine revealed that maropitant (0.1–10 µM) increased frequency of contraction, decreased amplitude of contraction and totally inhibited motility index in a concentration-dependent manner. We measured intestinal transit in vivo by measuring transportation of orally administered luminal content labeled with phenol red. Our results demonstrated that maropitant (10 mg/kg, SC) delayed intestinal transit. Geometric center value was significantly decreased in maropitant-treated mice. Anti-inflammatory effects of maropitant against leukocytes infiltration into the intestinal smooth muscle layer in post-operative ileus (POI) model mice were measured by immunohistochemistry. In POI model mice, a great number of CD68-positive macrophages or MPO-stained neutrophils infiltrated into the inflamed muscle region of the intestine. However, in the maropitant treated mice, the infiltration of leukocytes was not inhibited. The results indicated that maropitant has ability to induce disorder of intestinal motility in mice, but has no anti-inflammatory action in the mouse of a POI model. In conclusion, in mice, maropitant induces disorder of intestinal motility in vivo.     

Expression of the ether-a-go-go (ERG) potassium channel in smooth muscle of the equine gastrointestinal tract and influence on activity of jejunal smooth muscle

OBJECTIVE: To determine whether ether-a-go-go (ERG) potassium channels are expressed in equine gastrointestinal smooth muscle, whether ERG channel antagonists affect jejunal muscle contraction in vitro, and whether plasma cisapride concentrations in horses administered treatment for postoperative ileus (POI) are consistent with ERG channels as drug targets. SAMPLE POPULATION: Samples of intestinal smooth muscle obtained from 8 horses free of gastrointestinal tract disease and plasma samples obtained from 3 horses administered cisapride for treatment of POI. PROCEDURE: Membranes were prepared from the seromuscular layer of the duodenum, jejunum, ileum, cecum, large colon, and small colon. Immunoblotting was used to identify the ERG channel protein. Isolated jejunal muscle strips were used for isometric stress response to ERG channel blockers that included E-4031, MK-499, clofilium, and cisapride. Plasma concentrations of cisapride were determined in 3 horses administered cisapride for treatment of POI after small intestinal surgery. RESULTS: Immunoblotting identified ERG protein in all analyzed segments of the intestinal tract in all horses. The selective ERG antagonist E-4031 caused a concentration-dependent increase in jejunal contraction. Clofilium, MK-499, and cisapride also increased jejunal contraction at concentrations consistent with ERG channel block; effects of E-4031 and cisapride were not additive. Peak plasma cisapride concentrations in treated horses were consistent with ERG block as a mechanism of drug action. CONCLUSIONS AND CLINICAL RELEVANCE: The ERG potassium channels modulate motility of intestinal muscles in horses and may be a target for drugs. This finding may influence development of new prokinetic agents and impact treatment of horses with POI.     

5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist

The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.     

Effect of the liquid form of traditional Chinese medicine,Hozen-S,on gastric motility in dogs

Juzen-taiho-to, a traditional Chinese herbal medicine, is used for patients with anorexia and fatigue in human medicine. In our previous study, granulated Juzen-taiho-to improved vincristine-induced gastrointestinal adverse effects through increasing gastric motility in dogs. As the effect of Hozen-S, the sweet liquid form of Juzen-taiho-to, on dog gastric motility has not been investigated, we examined the effect of administration of Hozen-S on gastric motility. Furthermore, we assessed dog plasma ghrelin level to further elucidate the mechanism of the effect of Hozen-S on gastric contraction. Finally, we assessed the palatability of Hozen-S compared to granulated Juzen-taiho-to and its effect on body weight in dogs. Administration of Hozen-S significantly increased gastric motility, plasma ghrelin concentration, and body weight. A palatability evaluation revealed that the dogs preferred Hozen-S to granulated Juzen-taiho-to. In conclusion, Hozen-S administration to dogs promoted gastric motility by raising plasma ghrelin levels. Considering these functional and palatability data, Hozen-S may replace granulated type Juzen-taiho-to and become a prominent traditional Chinese veterinary medicament.     

The effects of medetomidine and xylazine on gastrointestinal motility and gastrin release in the dog

The effect of medetomidine, a potent and highly selective α₂-adrenoceptor agonist, on the motility of the gastric antrum, duodenum, mid-jejunum and ileum was investigated in ten dogs. Its effect on the release of gastrin was also determined. Administration of medetomidine intramuscularly (i.m.) at a dose of 40 μg/kg inhibited the motility of the gastric antrum, duodenum, mid-jejunum and ileum significantly, in comparison to administration of xylazine intramuscularly at a dose of 2.0 mg/kg. The release of gastrin was also significantly decreased in dogs receiving medetomidine. It was found to inhibit the motility in the gastric antrum and duodenum longer than in the mid-jejunum and ileum, presumably by acting specifically on α₂-adrenoceptors, likely at the peripheral level. Medetomidine also inhibited the gastric contraction associated with gastrin secretion.     

Ultrasonographic evaluation of reticular motility during rest, eating, rumination and stress in 30 healthy cows

A 3.5 MHz linear transducer was used to assess the motility of the reticulum in 30 healthy, standing, non-sedated cows while they were at rest, eating, ruminating and under stress. The ultrasonographic examinations were made over periods of nine minutes and video recorded for analysis. The reticulum contracted in a biphasic pattern while the cows were resting, eating or stressed. The first contraction was incomplete and was followed by a period of incomplete relaxation. A complete second contraction occurred immediately afterwards, followed by an interval of complete relaxation and the return of the organ to its original position. When the cows were ruminating, a regurgitation contraction, which was incomplete, occurred immediately before the biphasic contraction. The number of reticular contractions in a nine-minute period was largest when the cows were eating (13.9 contractions, or approximately 1.5 per minute) and smallest when they were stressed (9.3 contractions, or approximately 1 per minute). The duration of the first reticular contraction was shortest during rumination (2.4 seconds) and longest when the cows were eating (3.0 seconds). The interval between two biphasic contractions was shortest when the cows were eating (31.6 seconds) and longest when they were stressed (53.8 seconds).     

Purinergic P2X7 receptor antagonist ameliorates intestinal inflammation in postoperative ileus

Postoperative ileus (POI) is a postsurgical gastrointestinal motility dysfunction caused by mechanical stress to the intestine during abdominal surgery. POI leads to nausea and vomiting reduced patient quality of life, as well as high medical costs and extended hospitalization. Intestinal inflammation caused by macrophages and neutrophils is thought to be important in the mechanism of POI. Surgery-associated tissue injury and inflammation induce the release of adenosine triphosphate (ATP) from injured cells. Released ATP binds the purinergic P2X7 receptor (P2X7R) expressed on inflammatory cells, inducing the secretion of inflammatory mediators. P2X7R antagonists are thought to be important mediators of the first step in the inflammation process, and studies in chemically induced colitis models confirmed that P2X7R antagonists exhibit anti-inflammatory effects. Therefore, we hypothesized that P2X7R plays an important role in POI. POI models were generated from C57BL/6J mice. Mice were treated with P2X7R antagonist A438079 (34 mg/kg) 30 min before and 2 hr after intestinal manipulation (IM). Inflammatory cell infiltration and gastrointestinal transit were measured. A438079 ameliorated macrophage and neutrophil infiltration in the POI model. Impaired intestinal transit improved following A438079 treatment. P2X7R was expressed on both infiltrating and resident macrophages in the inflamed ileal muscle layer. The P2X7R antagonist A438079 exhibits anti-inflammatory effects via P2X7R expressed on macrophages and therefore could be a target in the treatment of POI.     

Dietary carbohydrate modifies the density of L cells in the chicken ileum

Glucagon-like peptides (GLPs) are secreted from intestinal L cells and stimulate various physiological functions in the gastrointestinal tract. The secretion of GLPs is influenced by macronutrient ingestion. This study aims to clarify the effects of dietary carbohydrate (CHO) on L cells in the chicken ileum. Six-week-old, male White Leghorn chickens were divided into three groups: control, low-CHO and CHO-free, with five chickens in each group. Paraffin sections were made from the proximal and distal ileum of each animal and subjected to immunohistochemistry for GLP-1 and GLP-2 peptides and in situ hybridization for proglucagon (PG) mRNA. A significant reduction of GLP-1- and GLP-2-immunoreactive cells was observed in the two experimental groups compared with that in the control. A reduction of cells expressing PG mRNA was observed in the proximal and distal ileum of the CHO-free group compared with that in the control. The ratio of GLP-1-immunoreactive cells showing Ki-67 immunoreactivity was significantly lower in the distal ileum of the CHO-free group than that in the control group. These data suggest that dietary CHO is an effective stimulator for modifying L cell density in the chicken ileum.     

Stress exposure during the preimplantation period affects blastocyst lineages and offspring development

We found retardation of preimplantation embryo growth after exposure to maternal restraint stress during the preimplantation period in our previous study. In the present study, we evaluated the impact of preimplantation maternal restraint stress on the distribution of inner cell mass (ICM) and trophectoderm (TE) cells in mouse blastocysts, and its possible effect on physiological development of offspring. We exposed spontaneously ovulating female mice to restraint stress for 30 min three times a day during the preimplantation period, and this treatment caused a significant increase in blood serum corticosterone concentration. Microscopic evaluation of embryos showed that restraint stress significantly decreased cell counts per blastocyst. Comparing the effect of restraint stress on the two blastocyst cell lineages, we found that the reduction in TE cells was more substantial than the reduction in ICM cells, which resulted in an increased ICM/TE ratio in blastocysts isolated from stressed dams compared with controls. Restraint stress reduced the number of implantation sites in uteri, significantly delayed eye opening in delivered mice, and altered their behavior in terms of two parameters (scratching on the base of an open field test apparatus, time spent in central zone) as well. Moreover, prenatally stressed offspring had significantly lower body weights and in 5-week old females delivered from stressed dams, fat deposits were significantly lower. Our results indicate that exposure to stress during very early pregnancy can have a negative impact on embryonic development with consequences reaching into postnatal life.     

Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086

The effect of pre-treatment with a selective platelet-activating factor (PAF) antagonist, WEB 2086, on the actions of low-dose endotoxin was evaluated in ponies prepared with gastrointestinal strain gauges. Endotoxin (0.1 microgram/kg i.v.) produced a marked reduction in gastric contraction amplitude and rate, and an increased frequency and reduced duration of jejunal phase III activity fronts (AFs). WEB 2086 (6.6 mg/kg) administered i.v. 10 min before the endotoxin, produced significant antagonism (P less than 0.001) of the effect of endotoxin on gastric contraction amplitude and rate. The combination of WEB 2086 and endotoxin produced gastric contractions of significantly (P less than 0.01) higher frequency than in the control studies. WEB 2086 also reduced endotoxin-induced abnormal phase III AFs in the jejunum and increases in heart rate and packed cell volume. These results provide evidence that endogenous PAF plays a role in mediating the acute effects of endotoxin on equine gastrointestinal motility.     

ULTRASONOGRAPHIC EVALUATION OF GASTROINTESTINAL DISEASES IN SMALL ANIMALS

Sonographic findings of 18 dogs and four cats with gastrointestinal (GI) diseases were reviewed. Wall thickness, wall layer identification, wall symmetry, extension of the lesion, nature of the GI contents, motility, and regional and/or systemic involvement were recorded for each animal. Ultrasonographic appearance of gastrointestinal neoplasms, gastrointestinal obstruction, ileus, intussusception, inflammatory GI diseases, and congenital disorders are discussed.     

地衣芽孢杆菌对脂多糖应激仔猪肠道形态、肠黏膜抗氧化能力和免疫力的影响

本试验旨在研究地衣芽孢杆菌对脂多糖(LPS)应激仔猪肠道形态、肠黏膜抗氧化能力和免疫力的影响。试验选用35日龄、平均体重为(10.0±0.5)kg的苏山猪90头,随机分成3组(对照组、LPS组和BL+LPS组),每组3个重复,每个重复10头仔猪。其中,对照组和LPS组仔猪均饲喂基础饲粮;BL+LPS组仔猪饲喂添加500 mg/kg地衣芽孢杆菌的基础饲粮。预试期3 d,正试期21 d,于正试期第21天从每个重复中选2头仔猪腹腔注射LPS(LPS组和BL+LPS组)或等量的灭菌生理盐水(对照组),注射24 h后屠宰取样。结果显示:1)与对照组相比,LPS应激显著降低了仔猪十二指肠二胺氧化酶(DAO)、空肠一氧化氮合成酶(NOS)活性及空肠一氧化氮(NO)含量(P<0.05),显著提高了血浆中NO含量和NOS活性(P<0.05);显著降低了空肠绒毛高度和绒隐比、回肠绒隐比(P<0.05);显著降低了十二指肠、空肠和回肠谷胱甘肽过氧化物酶(GSH⁃Px)、十二指肠和回肠超氧化物歧化酶(SOD)活性(P<0.05);显著降低了空肠上皮细胞中淋巴细胞、空肠和回肠上皮细胞中杯状细胞数量(P<0.05);显著降低了血清免疫球蛋白G(IgG)含量,提高了回肠黏膜白细胞介素-6(IL⁃6)和白细胞介素-1β(IL⁃1β)含量(P<0.05)。2)与LPS组相比,饲粮添加地衣芽孢杆菌显著提高了LPS应激仔猪回肠DAO和NOS活性(P<0.05);显著提高了空肠黏膜GSH⁃Px活性显著提高(P<0.05),显著降低了十二指肠黏膜丙二醛(MDA)含量(P<0.05);显著提高了血清IgG含量(P<0.05)。由此可见,LPS应激导致仔猪肠黏膜损伤,在饲粮中添加地衣芽孢杆菌可提高LPS应激仔猪的肠黏膜抗氧化能力和免疫力,一定程度上促进肠道形态的修复,减缓LPS应激导致的肠道损伤。     

Physiological responses of dietary tryptophan fed Labeo rohita to temperature and salinity stress

Two experiments were conducted to elucidate the possible effects of dietary L‐tryptophan (TRP) in Labeo rohita based on growth performance and physio‐biochemical responses. In the experiment I, a 60‐day feeding trial was carried out to elucidate the effects of dietary TRP enrichment on growth performance and physio‐biochemical responses. In the experiment II, the TRP pre‐fed L. rohita, from experiment I, was exposed to temperature and salinity stress to evaluate stress‐mitigating efficacy of TRP. In L. rohita, dietary supplementation of TRP showed significant effect on weight gain percentage and feed conversion ratio but not on blood glucose. A significant increase in RNA content and RNA/DNA ratio upon TRP supplementation was observed and was positively correlated with growth performance. The results of experiment II indicated that weight gain percentage, serum T3 and T4 levels were significantly reduced in groups that were exposed to temperature and salinity stress and fed diets without TRP supplementation. However, dietary supplementation of TRP significantly augmented weight gain percentage in stress‐exposed groups. Tryptophan supplementation helped in bringing back T3 and T4 levels comparable with control. A significant increase in superoxide dismutase, catalase, Adenosine triphosphatase, blood glucose and serum cortisol was observed in temperature‐ and salinity‐exposed groups fed without TRP‐supplemented diets. However, TRP supplementation was found to be effective in restoring the above parameters. The results of these experiments suggest that dietary TRP supplementation augments growth, lowers energy demand and helps in mitigating thermal and salinity stress in L. rohita.     

Effect of Alcohol Extract from Different Parts of Sophora alopecuroides on the Motility of Isolated Rat Small Intestine

To explore the effect of extract from different parts of Sophora alopecuroides picked in autumn on gastrointestinal motility, alcohol extract of bean, pod, leaf and shoot apex of Sophora alopecuroides at increasing dose(0.5% to 8.0%) were added to Tyrode's solution where rat isolated small intestine were bathed.The motility of small intestine was recorded by biological signal processing system.The results showed that the contract frequency and amplitude were significantly decreased when the concentration of each parts of Sophora alopecuroides reached 2.0% to 4.0% compared with that before treatment(P<0.05) and it was the dose dependent relation ship, but had no significant effect on the contract tension(P>0.05).Moreover, the inhibition effect of bean was the strongest among the four parts.Alcohol extract of bean at a dose of 2.0% inhibited the excitatory effect caused by cholinergic M-agonists, bethanechol, and the inhibition couldn't be reversed.The results concluded that different parts of Sophora alopecuroides could inhibit the contraction of rat small intestine, and the inhibition might happen partly by blocked M-receptor, indicating that Sophora alopecuroides are expected to be used to relieve gastrointestinal over contraction due to some reasons.     

苦豆子植株不同部位醇提液对大鼠离体小肠运动的影响

为比较秋季苦豆子植株不同部位提取物对消化道运动的干预作用,本研究利用生物信号处理系统测定了浓度递增(0.5%~8.0%)的苦豆子植株不同部位(豆子、豆荚、叶和顶须)醇提液对大鼠离体小肠平滑肌运动的影响,并初步探究其机理。结果显示,与用药前相比,苦豆子植株各部位均在浓度递增到2.0%~4.0%时使离体小肠收缩频率和幅度减小(P<0.05),并呈剂量依赖关系,而对收缩张力影响不显著(P>0.05),其中豆子抑制作用最强。同时,胆碱能M-受体激动剂氯贝胆碱引起的小肠平滑肌兴奋作用可被2.0%豆子完全抑制,且2.0%豆子的抑制作用不能被氯贝胆碱扭转。结果表明,苦豆子植株各部位对离体小肠运动均有抑制作用,且可能与阻断M-受体作用有关。提示苦豆子植株各部位有望用于缓解由于某些原因引起的胃肠活动过度症状。     

Surgical diseases of the small intestine.

Surgical disorders of the gastrointestinal tract of cattle occur occasionally, and veterinarians are challenged to determine an accurate diagnosis and treatment for these conditions. Although surgical diseases most commonly occur in the forestomachs (dislocated abomasum, reticuloperitonitis) and the colons (cecal dilatation), this article focuses on lesions in the small intestine (duodenum, jejunum, ileum).     

Intestinal surgery of adult cattle.

Surgical disorders of the gastrointestinal tract of cattle occur occasionally, and veterinarians are challenged to determine an accurate diagnosis and treatment for these conditions. Although surgical diseases most commonly occur in the forestomachs (dislocated abomasum, reticuloperitonitis) and the colons (cecal dilation), this article focuses n lesions in the small intestine (duodenum, jejunum, ileum).     

COMPARATIVE ORGAN IMAGING: THE GASTROINTESTINAL TRACT

Diagnostic radiology of the esophagus, stomach, small and large intestine, mesentery, and pancreas is reviewed. Survey and contrast radiography remain the principal imaging methods used to evaluate gastrointestinal diseases in animals. Of the other imaging techniques, scintigraphy has potential in assessment of esophageal and gastric motility disorders, and detection of intestinal hemorrhage. Ultrasonography is useful for imaging the pancreas and gastrointestinal mass lesions.