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.     

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).     

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.     

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。     

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.     

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。     

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.     

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.     

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.     

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).     

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).     

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.     

Effects of Temperature Changes on the Contractility of Isolated Small Intestinal Smooth Muscle in Rabbits

In order to explore the influence of temperature changes on animal digestive tract smooth muscle,the contractility of isolated rabbit small intestine (duodenum,jejunum and ileum) were measured at different temperatures (39→32℃,32→39℃,39→42℃ and 42→39℃) using the biological signal processing system.The results showed that the contraction frequency of duodenum and jejunum was positively correlated with temperature changes between 39 and 32℃,while the amplitude and tension of duodenum were negatively correlated with temperature changes.Only the contraction frequency of ileum was positively correlated with temperature changes between 39 and 32℃.Changes of frequency,amplitude and tension of duodenum between 39 and 42℃ were similar with those changes between 39 and 32℃.However,the contraction of jejunum and ileum was irregular.When the temperature was decreased from 42 to 39℃,the contraction of small intestine could not return to the condition in 39℃.The results suggested that the optimal bath temperature was 37℃ in contraction test of rabbit small intestine in vitro,and the present results could be referenced to explore the disorder of gastrointestinal movement due to the change of environment temperature in animals.     

温度变化对家兔离体小肠平滑肌运动的影响

为了探究温度变化对动物消化道平滑肌运动的影响,本试验用生物信号处理系统测定了浴槽不同温度（39→32℃、32→39℃、39→42℃和42→39℃）对家兔离体小肠各段（十二指肠、空肠、回肠）平滑肌运动的影响。结果显示,当温度在39和32℃之间变化时家兔离体十二指肠和空肠运动的收缩频率同温度变化呈正相关,而十二指肠收缩幅度和收缩张力同温度变化呈负相关,但回肠仅表现在收缩频率同温度变化呈正相关;当温度从39℃升高到42℃时,十二指肠的收缩频率、收缩幅度和收缩张力变化与温度在39和32℃之间变化情况相同,但是空肠和回肠的规律性较差;当温度从42℃高温降低到39℃时,3段离体小肠运动不能恢复到39℃时的运动状态,家兔小肠离体试验浴槽最适温度为37℃。本研究结果提示,在进行动物小肠离体试验时应注意浴槽温度对小肠运动的影响,同时本研究结果也为探究由于环境温度变化导致的动物胃肠运动异常的机理提供参考。