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1.
Shoma MIKAWA Shohei YAMAMOTO Md Shafiqul ISLAM Noriyuki KAJI Takahisa MURATA Risuke MIZUNO Hiroshi OZAKI Masatoshi HORI 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(10):1195-1199
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. 相似文献
2.
3.
Mari Spildrejorde Stephen J. Curtis Belinda L. Curtis Ronald Sluyter 《Veterinary immunology and immunopathology》2014,157(1-2):105-110
Binding of extracellular adenosine 5′-triphosphate (ATP) or lipopolysaccharide (LPS) to the damage-associated molecular pattern receptor P2X7 or the pathogen-associated molecular pattern receptor Toll-like receptor (TLR)4, respectively, can induce the release of the pleiotropic cytokine interleukin (IL)-1β in humans and mice. However, the release of IL-1β in dogs remains poorly defined. Using a canine IL-1β enzyme-linked immunosorbent assay, this study investigated whether ATP or LPS could induce IL-1β release in a canine blood-based assay. Short-term incubations (30 min) with ATP induced IL-1β release in LPS-primed canine blood, and this process could be near-completely impaired by the P2X7 antagonist, A438079. In contrast, ATP failed to induce IL-1β release from blood not primed with LPS. ATP-induced IL-1β release was observed with LPS-primed blood from eight different pedigrees or cross breeds. Long-term incubations (24 h) with LPS induced IL-1β release in canine blood in a concentration-dependent manner. This process was not altered by co-incubation with A438079. LPS-induced IL-1β release was observed with blood from 10 different pedigrees or cross breeds. These results demonstrate that both extracellular ATP and LPS can induce IL-1β release in dogs, and that ATP- but not LPS-induced IL-1β release in blood is dependent on P2X7 activation. These findings support the role of both P2X7 and TLR4 in IL-1β release in dogs. 相似文献
4.
P2X7 is an ATP gated purinoceptor that has been linked to various immune responses. P2X7 appears to be expressed ubiquitously in the immune system and thus may be important as an effector pathway or play significant roles in cell activation/death. 2',3'-(4-Benzoyl)benzoyl ATP is the most potent agonist of this receptor and ATP in its fully dissociated form (ATP(4-)) also activates the receptor. High concentrations of ATP can cause the P2X7 receptor to induce pore formation on the surface of the cell that allows molecules of considerable size to pass and can lead to cell death. The P2X7 receptor has also been linked to various immune activities when the concentration of ATP is lower, including the release of IL-1beta. The role P2X7 receptors have on immune cell activities is just beginning to be understood. We sought to determine the role of P2X7 on bovine macrophages in eliminating the causative agent of bovine-type tuberculosis, Mycobacterium bovis. Because high concentrations of ATP are linked to macrophage death, we determined if this method of cell destruction also leads to reduced bacterial viability. We find that P2X7 is present on bovine macrophages from different sources, including both peripheral blood-derived as well as alveolar macrophages. In addition, P2X7 mRNA is present in B and T lymphocytes. The treatment of M. bovis-infected macrophages with ATP results in reduced macrophage viability as well as reduced M. bovis viability. 相似文献
5.
REASONS FOR PERFORMING STUDY: Post operative ileus (POI) remains an important cause of post operative morbidity and mortality in the horse. However, clinical progression of naturally occurring cases of POI in both horse and man does not entirely support the 'neurogenic' hypothesis as the sole mechanism of POI; and the hypothesis that inflammation plays a major role at 12-24 h after surgery requires validation. HYPOTHESIS: An inflammatory infiltrate in the muscularis externa and myenteric plexus of equine jejunum is present 18 h following a period of ischaemia. METHODS: Samples of normal jejunum, jejunum from the proximal resection margins of clinical cases and jejunum obtained 18 h after 1 or 2 h ischaemia or manipulation alone were evaluated for neutrophil infiltration. Samples obtained 18 h after surgery were additionally evaluated for leucocyte activation using calprotectin immunohistochemistry. Results were evaluated by ANOVA and P < 0.05 was considered significant. RESULTS: Significant neutrophilic inflammation was identified in the samples from the proximal resection margins of clinical cases compared to uninjured jejunum. In experimental cases, neutrophilic inflammation appeared to be increased further by 18 h and was identified through all intestinal layers, particularly in the serosa, fascial planes around circular and longitudinal muscle fibres, and myenteric plexus. This elevated level of neutrophilic inflammation was mirrored by an increased number of calprotectin-positive cells in these intestinal layers, indicating leucocyte activation. CONCLUSIONS: Significant neutrophilic inflammation occurs in equine jejunal myenteric layers 18 h after surgery. POTENTIAL RELEVANCE: This neutrophilic inflammation coincides with the clinical time point at which POI is identified and may indicate that inflammatory pathways, rather than solely neurogenic pathways, are responsible for POI in the horse. 相似文献
6.
Lillich JD Rakestraw PC Roussel AJ Finley MR Ganta S Freeman LC 《American journal of veterinary research》2003,64(3):267-272
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. 相似文献
7.
OBJECTIVE: To report prokinetic strategies used to manage horses after gastrointestinal surgery. DESIGN: Electronic questionnaire. SAMPLE POPULATION: Diplomates of the American College of Veterinary Surgeons (ACVS) who perform equine intestinal surgery. PROCEDURE: A survey (21 questions) designed to determine use of prokinetic agents was sent electronically to 112 ACVS Diplomates known to perform equine intestinal surgery. Several clinical scenarios were also described to determine which, if any, prokinetic agent respondents would select. RESULTS: Responses were obtained from 58 (52%) surgeons from 44 clinics. Selection of prokinetic agent for specific gastrointestinal conditions was relatively uniform whereas there was considerable variation in dose administered. For postoperative ileus (POI) associated with most intestinal lesions, 2% lidocaine was most commonly selected. Other prokinetics in decreasing frequency of use were erythromycin lactobionate, metoclopramide, and cisapride. Prokinetic agents were more commonly administered after small intestine strangulating obstructions and less commonly for large intestinal lesions. No novel agents were identified by respondents. CONCLUSIONS: Prokinetic drugs are commonly used for the management and/or attenuation of POI in horses, but dosages and routes of administration are variable. CLINICAL RELEVANCE: Although prokinetics are commonly used for management of POI in horses there is clearly a need for more controlled studies to define efficacious dosing and a need to develop new prokinetic drugs. 相似文献
8.
SUSAN J. HOLCOMBE VMD PhD Diplomate ACVS & ACVECC KATIE M. RODRIGUEZ DVM JENNIFER L. HAUPT BS JAMES O. CAMPBELL DVM KRISTIN P. CHANEY DVM HOLLY D. SPARKS DVM JOE G. HAUPTMAN DVM Diplomate ACVS 《Veterinary surgery : VS》2009,38(3):368-372
Objectives— To determine the incidence of postoperative ileus (POI) in a population of horses after small intestinal surgery and the effect of multiple variables on development of POI.
Study Design— Case series.
Animals— Horses (n=233) aged ≥1 year that had exploratory celiotomy for small intestinal disease that recovered from surgery from 1995 to 2005.
Methods— Sixty-eight variables were collected from medical records (1995–2005) for each horse. POI was defined as nasogastric reflux volume >20 L over 24 hours or >8 L at any single time after surgery.
Results— Twenty-seven percent (64/233) of horses developed POI; 29 of 64 (46%) horses with POI had duodenitis proximal jejunitis (DPJ). When no intestinal resection was required at surgery, excluding horses with DPJ, 15% of horses had POI; 30% horses had POI after intestinal resection. Ten percent of horses had POI for >24 hours. When horses with DPJ were excluded, factors associated with increased risk of POI included high packed cell volume at hospital admission ( P =.024), increasing age ( P =.0004), and length of intestinal resection ( P =.05).
Conclusions— Risk factors for POI in this study were nonspecific although horses with intestinal resection are at higher risk compared with horses without intestinal resection.
Clinical Relevance— Predicting with certainty which cases will develop POI remains elusive. 相似文献
Study Design— Case series.
Animals— Horses (n=233) aged ≥1 year that had exploratory celiotomy for small intestinal disease that recovered from surgery from 1995 to 2005.
Methods— Sixty-eight variables were collected from medical records (1995–2005) for each horse. POI was defined as nasogastric reflux volume >20 L over 24 hours or >8 L at any single time after surgery.
Results— Twenty-seven percent (64/233) of horses developed POI; 29 of 64 (46%) horses with POI had duodenitis proximal jejunitis (DPJ). When no intestinal resection was required at surgery, excluding horses with DPJ, 15% of horses had POI; 30% horses had POI after intestinal resection. Ten percent of horses had POI for >24 hours. When horses with DPJ were excluded, factors associated with increased risk of POI included high packed cell volume at hospital admission ( P =.024), increasing age ( P =.0004), and length of intestinal resection ( P =.05).
Conclusions— Risk factors for POI in this study were nonspecific although horses with intestinal resection are at higher risk compared with horses without intestinal resection.
Clinical Relevance— Predicting with certainty which cases will develop POI remains elusive. 相似文献
9.
Sutton S Clutterbuck A Harris P Gent T Freeman S Foster N Barrett-Jolley R Mobasheri A 《Veterinary journal (London, England : 1997)》2009,179(1):10-24
Osteoarthritis (OA) is one of the most common and disabling chronic joint disorders affecting horses, dogs and humans. Synovial inflammation or synovitis is a frequently observed phenomenon in osteoarthritic joints and contributes to the pathogenesis of OA through formation of various catabolic and pro-inflammatory mediators altering the balance of cartilage matrix degradation and repair. Catabolic mediators produced by the inflamed synovium include pro-inflammatory cytokines, nitric oxide, prostaglandin E(2) and several neuropeptides, which further contribute to the pathogenesis of OA by increasing cartilage degradation. Recent studies suggest that substance P, corticotropin-releasing factor, urocortin and vasoactive intestinal peptide may also be involved in OA development, but the precise role of these neuropeptides in the pathogenesis of OA is not known. Since increased production of matrix metalloproteinases by the synovium is stimulated by pro-inflammatory cytokines, future anti-inflammatory therapies should focus on the synovium as a means of controlling subsequent inflammatory damage. 相似文献
10.
O.A Garden H.C Rutgers S.H Sørensen S Daniels D Walker R.M Batt 《Research in veterinary science》1997,63(3):257
A reference range was determined for a combined test of differential sugar permeability, using lactulose (L) and rhamnose (R), and intestinal function, using D-xlylose (X) and 3-O-methylglucose (G), in clinically healthy adult Irish setter dogs. Urinary L/R ratios in 48 Irish setters from one to 12 years old varied from 0·03 to 0·18, with a mean (
) of 0·10 (0·01); X/G ratios varied from 0·46 to 0·81, with a mean (
) of 0·59 (0·01). There were no significant differences between L/R or X/G ratios of dogs of different sex (P>0·2) or age (P0·5), using analysis of covariance. Lactulose/rhamnose ratios of ≥0·18 and X/G ratios ≥0·43 were considered normal, defined by the respective mean ± 2
. Repeatability was established by performing three permeability and function tests at monthly intervals in twelve of the dogs. Analysis of repeated L/R and X/G ratios by means of linear models procedure revealed no significant differences between measurements made on successive occasions (P>0·15), confirming the repeatability of this test. 相似文献
11.
Present Concepts on the Inflammatory Modulators with Special Reference to Cytokines* 总被引：2，自引：0，他引：2
Van Miert AS 《Veterinary research communications》2002,26(2):111-126
The pro- and anti-inflammatory cytokines create a network of interactions between cells that lead to both stimulatory and inhibitory responses that maintain an effective homeostatic regulation. The anti-inflammatory cytokines are a family of peptides that modulate the pro-inflammatory cytokine response. Cytokines act in concert with non-cytokine mediators, such as prostaglandin E2, glucocorticosteroids, lipocortins, and catecholamines. This review highlights new developments in our understanding of the pathophysiology of inflammation and gives an example of a more recent approach to the modulation of acute systemic inflammatory disorders: activation of 2-adrenergic receptors on macrophages. In this respect the potent 2-adrenergic agonist clenbuterol seems of therapeutic interest. 相似文献
12.
Z. M. Lisowski R. S. Pirie A. T. Blikslager D. Lefebvre D. A. Hume N. P. H. Hudson 《Equine veterinary journal》2018,50(3):292-303
Post‐operative ileus (POI) is a serious condition which any horse undergoing abdominal surgery is at risk of developing, leading to increased hospitalisation time and resulting costs. Advances in the understanding of the development of equine POI are mainly based on human and rodent literature, where manipulation‐induced inflammation has been identified as a trigger, with activation of resident muscularis externa macrophages playing a crucial role in the pathophysiology. Despite many pharmacological trials in all species, there is no single completely successful treatment for POI, highlighting that the condition is multifactorial in cause and requires a multimodal approach to minimise its incidence. 相似文献
13.
Gross and histologic lesions of paratuberculosis were studied in water buffaloes. Small intestines and associated mesenteric lymph nodes of 405 water buffaloes were examined. Of these, 20 animals having visible changes of intestinal thickening, mucosal corrugations, and enlargement of mesenteric lymph nodes exhibited histologic alteration characteristics of mild to moderate granulomatous inflammation. The histologic lesions observed in these animals were classified into 3 grades on the basis of type of cellular infiltration, granuloma formation, and presence of acid-fast bacilli. Grade-1 lesions observed in 8 animals were marked by the presence of scattered epithelioid macrophages amid large number of lymphocytes in the intestinal villi and in the paracortical regions of the associated mesenteric lymph nodes. Another 8 animals classified under grade-2 revealed microgranulomas, infiltration with a larger number of epithelioid macrophages besides lymphocytes in the intestinal villi, and granulomas in the mesenteric lymph nodes. Grade-3 lesions observed in 4 animals were characterized by the presence of epithelioid granulomas and giant cells in the intestines and the mesenteric lymph nodes. The Ziehl-Neelsen's stained tissue sections revealed acid-fast bacilli in grade-3 and -2 animals and acid-fast granular debris in grade-1 animals. Among these 20 buffaloes, 14 (70%) were positive in the IS900 specific polymerase chain reaction and 6 (30%) were positive in the bacterial culture. 相似文献
14.
Fujimoto Y Nakatani N Kubo T Semi Y Yoshida N Nakajima H Iseri T Azuma YT Takeuchi T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2012,74(1):27-34
Macrophages are essential for controlling the majority of infections, and are mediators of natural immunity. During infection, lipopolysaccharide (LPS) stimulates macrophages to produce pro-inflammatory cytokines. Adenosine and ATP released into the extracellular space by immunological stimuli have been shown to regulate various immune functions. More recently, it has been shown adenosine and ATP have a critical role on the physiological negative feedback mechanism for limitation and termination of tissue-specific and systemic inflammatory responses. It was useful and meaningful to gain information about interaction between LPS, which generates the inflammation, and adenosine and ATP, which terminate the inflammation. We evaluate effects of adenosine and ATP on the production of cytokines related to inflammation in canine macrophage cell line DH82 cells. Adenosine and ATP respectively increased the production of IL-10 without affecting the production of IL-6, TNF-α and IL-12 in DH82 cells. In addition, adenosine and ATP prevented the production of LPS-induced IL-6, TNF-α and IL-12 in DH82 cells. In contrast, adenosine and ATP potentiated LPS-induced IL-10 production in DH82 cells. Moreover, adenosine, but not ATP inhibited LPS-induced expression of TLR4 in DH82 cells. These results suggest that conditions related to increased adenosine and/or ATP may play an important role in the inflammatory reactions. 相似文献
15.
Allenspach K Steiner JM Shah BN Berghoff N Ruaux C Williams DA Blum JW Gaschen F 《American journal of veterinary research》2006,67(3):479-483
OBJECTIVE: To assess intestinal mucosal function by measuring permeability and absorptive capacity in dogs with chronic enteropathy (CE) before and after treatment and to determine whether those variables were correlated with clinical disease activity or histologic scoring of intestinal biopsy specimens. ANIMALS: 29 dogs with CE. PROCEDURE: Dogs were designated as having dietresponsive CE or CE requiring glucorticoid treatment. Severity of clinical signs was assessed by calculating the canine inflammatory bowel disease activity index (CIBDAI). Histologic severity of intestinal infiltration was assessed before and after 4 weeks of treatment in the diet-responsive group and before and after 10 weeks of treatment in the glucocorticoid group. Gastrointestinal permeability and mucosal absorptive capacity were assessed by use of intragastric administration of a solution containing lactulose, rhamnose, xylose, 3-O-methylglucose, and sucrose. Urine was collected 6 hours after administration of the sugar solution to determine urinary lactulose-to-rhamnose (L:R), xylose-to-methylglucose (X:M), and sucrose-to-methylglucose (S:M) ratios. RESULTS: Median CIBDAI scores decreased significantly in both groups of dogs after treatment. However, the median histologic grade of intestinal biopsy specimens did not change with treatment in either group. There were no significant differences in L:R, X:M, or S:M ratios after treatment in either group and no significant correlations between L:R, X:M, or S:M ratios and CIBDAI or histologic scores. CONCLUSIONS AND CLINICAL RELEVANCE: Results of tests for intestinal permeability and mucosal absorptive capacity were not useful indicators of clinical disease activity as assessed by the CIBDAI or the sever ity of infiltration as indicated by histologic evaluation. 相似文献
16.
U. Schwittlick J. Junginger K. Hahn A. Habierski M. Hewicker‐Trautwein 《Anatomia, histologia, embryologia》2017,46(1):33-42
Histamine is an important mediator of many physiological processes including gastrointestinal function that acts via four different histamine receptors (H1R to H4R). Elevated histamine levels and increased HR messenger ribonucleic acid (mRNA) have been shown in humans with gastrointestinal disorders such as irritable bowel syndrome or allergic intestinal diseases. As there is limited knowledge concerning the distribution of histamine receptors (HR) in dogs, one aim of this study was to investigate the expression of histamine 1 receptor (H1R), histamine 2 receptor (H2R) and histamine 4 receptor (H4R) in the canine gastrointestinal tract at protein level using immunohistochemistry. Histamine 1 receptor, H2R and H4R were widely expressed throughout the canine gastrointestinal tract including epithelial, mesenchymal, neuronal and immune cells. In addition, in situ hybridisation was established for detecting canine H4R mRNA. Results showed H4R mRNA to be present in enterocytes, lamina propria immune cells and submucosal plexus in the duodenum and colon of nearly all investigated animals. The results elucidate the importance of HR in the canine gut and represent the basis for investigating their possible impact on canine inflammatory gastrointestinal disorders. 相似文献
17.
Equine post operative ileus: A review of current thinking on pathophysiology and management 
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下载免费PDF全文 Equine post operative ileus (POI) is a serious post surgical complication in the horse, with a significant fatality rate. Despite the ongoing debate with regard to both the clinical definition of equine POI and the optimal management of this condition, there is increasing awareness and acceptance, supported by scientific research, that inflammation plays a key role in its pathophysiology. This review aims to outline the current thinking on the pathophysiology and management of this condition, with reference to the published literature on equine, rodent and human POI. Although studies conducted in other species are likely to provide an abundant source of information with potentially useful translational applications for the equine condition, such an approach needs to be cognisant of potential interspecies differences both in the pathogenesis of the condition and in basic gastrointestinal physiology. 相似文献
18.
The action of low dose endotoxin on equine bowel motility 总被引：4，自引：0，他引：4
Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestine an increase in abnormally arranged regular activity and a decrease in irregular activity was observed. There was no significant prolongation in stomach to anus transit time as assessed by the passage of plastic spheres. The bowel motility patterns induced by endotoxin could be mimicked by the intravenous infusion of PGE2 and less potently by PGI2 (prostacyclin), but not by PGF2 alpha. This study provides evidence that systematic endotoxin present in clinical cases of colic may play a role in the pathogenesis of equine ileus. The acute effects of endotoxin on bowel motility appear to be mediated indirectly by prostaglandins, and the inhibitory effects may be mediated mainly by PGE2. 相似文献
19.
The etiological factors involved in diarrhea are multiple. Also the mechanisms and mediators involved are multiple: intracellular mediators (Ca, cAMP, cGMP, calmodulin, phospholipids), extracellular mediators (hormones, neurotransmitters, prostaglandins, enterotoxins...), intramural blood flow and oxygen, intestinal motility (local- and peristaltic motility). Till now, antidiarrheals are not so versatile that they provide a solution to all types of diarrhea. The mechanisms of action of fluid replacement therapy, loperamide, alpha 2 agonist and some nonsteroidal anti-inflammatory substances are reviewed. 相似文献
20.
The etiological factors involved in diarrhea are multiple. Also the mechanisms and mediators involved are multiple: intracellular mediators (Ca, cAMP, cGMP, calmodulin, phospholipids), extracellular mediators (hormones, neurotransmitters, prostaglandins, enterotoxins...), intramural blood flow and oxygen, intestinal motility (local- and peristaltic motility).Till now, antidiarrheals are not so versatile that they provide a solution to all types of diarrhea. The mechanisms of action of fluid replacement therapy, loperamide, alpha 2 agonist and some nonsteroidal anti-inflammatory substances are reviewed. 相似文献