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1.
Seven captive eastern box turtles (Terrapene carolina carolina) from a large collection of North American chelonians in North Carolina became acutely ill in the fall of 2002. Five of the turtles died. Clinical signs included cutaneous abscessation, oral ulceration or abscessation (or both), respiratory distress, anorexia, and lethargy. The predominant postmortem lesion was fibrinoid vasculitis of various organs, including skin, mucous membranes, lungs, and liver. No inclusion bodies were detected by histopathology or electron microscopy of formalin-fixed tissue. An iridovirus was isolated from tissues obtained postmortem from two of the box turtles that died. The virus was characterized by electron microscopy, polymerase chain reaction, and sequence analysis of a portion of the major capsid protein as a member of the genus Ranavirus.  相似文献   

2.
The pharmacodynamics of non-steroidal anti-inflammatory drugs (NSAIDs) are for the most part well-understood. All NSAIDs inhibit the enzyme cyclooxygenase (COX), and for this reason prostaglandin synthesis. Two isoforms of COX could be isolated. COX-1 is detectable in most tissues on a constant level and is responsible for the synthesis of prostaglandins with cytoprotective effects. COX-2 is induced through inflammation and supports the inflammatory process by producing pro-inflammatory prostaglandins. The desired effects of NSAIDs are related to inhibition of COX-2, whereas inhibition of COX-1 has been linked to the typical side-effects of NSAIDs, especially in the stomach and kidney. The great differences between effects and side-effects in the numerous substances can be explained because of different interactions of the NSAIDs on COX-1 and COX-2. In various test systems meloxicam has been shown to be a preferential inhibitor of COX-2. There are also large differences between the individual NSAIDs with regard to pharmacokinetics. Meloxicam is completely absorbed from the gastrointestinal tract and has an elimination half-life of 24 hours in the dog. It is excreted in faeces and urine. The metabolites, detectable in urine are biologically inactive and do not influence the prostaglandin synthesis in the kidney. In the underlying study, plasma concentration of meloxicam was determined after a subcutaneous injection of 0.2 mg/kg b. w. (day 1) followed by oral treatment of 0.1 mg/kg b. w. (days 2-14). The results confirm the recommended dosage regime of meloxicam with its initial loading dose and the subsequent maintenance dose. This dosing regime results in a very favourable curve of concentrations with a very rapidly attained steady state after roughly two days, without accumulation even in long-term treatment.  相似文献   

3.
OBJECTIVE: To evaluate cyclooxygenase isozyme distribution in tissues from dogs and determine the differential sensitivity of canine cyclooxygenase (COX)-1 and -2 isozymes to nonsteroidal anti-inflammatory drugs (NSAIDs). SAMPLE POPULATION: Canine tissue samples (stomach, duodenum, ileum, jejunum, colon, spleen, cerebral cortex, lung, ovary, kidney, and liver) were obtained from 2 dogs for northern and western blot analyses, and blood for whole blood COX assays was obtained from 15 dogs. PROCEDURE: 11 NSAIDs were evaluated to determine their COX-2 selectivity in whole blood assays. The concentrations of the drug needed to inhibit 50% of enzyme activity (IC50) were then calculated for comparison. Expression and tissue distribution of COX isozymes were determined by northern and western blot analysis. RESULTS: Aspirin, diclofenac, indomethacin, ketoprofen, meclofenamic acid, and piroxicam had little selectivity toward COX isozymes, whereas NS398, carprofen, tolfenamic acid, nimesulide, and etodolac had more than 5 times greater preference for inhibiting COX-2 than COX-1. All canine tissues examined, including those from the gastrointestinal tract, coexpressed COX-1 and -2 mRNA, although protein expression was observed only for COX-1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine COX-2 was selectively inhibited by etodolac, nimesulide, and NS398; tolfenamic acid and carprofen also appeared to be preferential COX-2 inhibitors in dogs. The roles of COX-1 as a constitutive housekeeping enzyme and COX-2 as a proinflammatory inducible enzyme (as determined in humans) appear to apply to dogs; therefore, COX-2-selective inhibitors should prove useful in reducing the adverse effects associated with nonselective NSAIDs.  相似文献   

4.

Objective

Quantify visual acuity of a semi-aquatic turtle species, Terrapene carolina triunguis (three-toed box turtles), utilizing optokinetic response/reflex/nystagmus.

Methods

Ten turtles were placed on a custom platform and an image of white and black gratings of varying sized widths was projected onto a white screen in front of the turtles. Optokinetic response (OKR) was observed through a web camera as well as physically by an observer. The grating sizes were decreased until OKR could not be elicited. The size of grating was recorded and was used to calculate visual acuity.

Results

The average visual acuity was 0.26 cycle per degree (cpd) with the highest recorded value being 0.43 cpd and lowest being 0.15 cpd. Neither sex nor weight were significantly associated with visual acuity (p = .24 and .98, respectively).

Conclusions

Visual acuity of these semi-aquatic turtles was much lower than previously reported visual acuities of aquatic turtles. This could be due to differences in refractive indices between water and air, behavioral adaptations for the different species and/or method of obtaining visual acuity.  相似文献   

5.
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6.
《Veterinary microbiology》2015,175(2-4):218-223
Herpesviruses are significant pathogens of chelonians which most commonly cause upper respiratory tract disease and necrotizing stomatitis. Herpesvirus infection was identified in two populations of captive Eastern box turtles (Terrapene carolina carolina) using histopathology and polymerase chain reaction (PCR) with DNA sequencing. Necrotizing lesions with eosinophilic to amphophilic intranuclear inclusion bodies were identified in the tissues of one hatch-year individual in January 2013, which was herpesvirus positive by PCR. A separate captive group of adults had an observed herpesvirus prevalence of 58% using PCR in July 2011. In these cases, a novel herpesvirus, Terrapene herpesvirus 1 (TerHV1), was identified and serves as the first herpesvirus sequenced in the genus Terrapene. Similar to the other herpesviruses of the Order Testudines, TerHV1 clusters with the genus Scutavirus of the subfamily Alphaherpesvirinae.  相似文献   

7.
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8.
1. Glucose transporter (GLUT) proteins, one of which is the major insulin-responsive transporter GLUT4, play a crucial role in cellular glucose uptake and glucose homeostasis in mammals. The aim of this study was to identify the extent of mRNA expression of GLUT1, GLUT2, GLUT3 and GLUT8 in chickens intrinsically lacking GLUT4. 2. GLUT1 mRNA was detected in most tissues of 3-week-old broiler chickens, with the highest expression measured in brain and adipose tissue. GLUT2 was expressed only in the liver and kidney. GLUT3 was highly expressed in the brain. GLUT8 was expressed ubiquitously, with expression in kidney and adipose tissue relatively higher than that of other tissues. 3. Expression levels of GLUT isoforms 1, 3 and 8 in skeletal muscle tissue were very low compared to the other tissues tested. 4. [3H]Cytochalasin B binding assays on tissue from 3-week-old chickens showed that the number of cytochalasin B binding sites in skeletal muscle plasma membranes was higher than in liver plasma membranes. These results suggest that GLUT proteins and/or GLUT-like proteins that bind cytochalasin B are expressed in chicken skeletal muscles. 5. It is proposed that GLUT expression and glucose transport in chicken tissues are regulated in a manner different from that in mammals.  相似文献   

9.
This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administration routes (but with delayed absorption in horses and ruminants after oral dosing), a high degree of binding to plasma protein, low volumes of distribution, limited excretion of administered dose as parent drug in urine, marked inter-species differences in clearance and elimination half-life and ready penetration into and slow clearance from acute inflammatory exudate. The therapeutic effects of NSAIDs are exerted both locally (at peripheral inflammatory sites) and centrally. There is widespread acceptance that the principal mechanism of action (both PD and toxicodynamics) of NSAIDs at the molecular level comprises inhibition of cyclooxygenase (COX), an enzyme in the arachidonic acid cascade, which generates inflammatory mediators of the prostaglandin group. However, NSAIDs possess also many other actions at the molecular level. Two isoforms of COX have been identified. Inhibition of COX-1 is likely to account for most of the side-effects of NSAIDs (gastrointestinal irritation, renotoxicity and inhibition of blood clotting) but a minor contribution also to some of the therapeutic effects (analgesic and anti-inflammatory actions) cannot be excluded. Inhibition of COX-2 accounts for most and possibly all of the therapeutic effects of NSAIDs. Consequently, there has been an intensive search to identify and develop drugs with selectivity for inhibition of COX-2. Whole blood in vitro assays are used to investigate quantitatively the three key PD parameters (efficacy, potency and sensitivity) for NSAID inhibition of COX isoforms, providing data on COX-1:COX-2 inhibition ratios. Limited published data point to species differences in NSAID-induced COX inhibition, for both potency and potency ratios. Members of the 2-arylpropionate sub-groups of NSAIDs exist in two enantiomeric forms [R-(-) and S-(+)] and are licensed as racemic mixtures. For these drugs there are marked enantiomeric differences in PK and PD properties of individual drugs in a given species, as well as important species differences in both PK and PD properties.  相似文献   

10.
OBJECTIVE: To assess expression of cyclooxygenase (COX)-1 and -2 in naturally occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in horses. SAMPLE POPULATION: Tissue samples collected from 3 conjunctival, 2 vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia. PROCEDURES: Tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until analysis. Protein was extracted from the frozen tissues, and western blot analyses were performed. Nonneoplastic and abnormal tissues from each body region were run on the same blot, and blots were run in triplicate. Molecular-weight markers and COX-1 and 2 ovine standards (positive control samples) were run concurrently on the gels; negative control samples were not used. RESULTS: All tissues, including the nonneoplastic and SCC tissues, expressed both COX-1 and -2 proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the expression of COX proteins in both nonneoplastic and SCC-affected tissues in horses is markedly different from that in other species. The reason for the potential benefit of COX-2 inhibitors in horses and other species is unknown. Further research needs to be performed to evaluate the efficacy of COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms of tumor development in horses should be performed to increase understanding of this disease and ascertain how the mechanisms differ from those in other animals.  相似文献   

11.
Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV, q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of LPS into one middle carpal joint. Synovial fluid was analyzed for white blood cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac significantly reduced WBC count 6 and 24-h following injection of LPS compared to untreated horses. In addition, both drugs significantly reduced PGE2 levels (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2 was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac may serve as a more selective anti-inflammatory agent than phenylbutazone for treatment of equine synovitis.  相似文献   

12.
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13.
Gastrointestinal disorders are an important cause of morbidity in box turtles (Terrapene carolina Carolina), however published information is currently lacking on the normal radiographic anatomy, transit, and emptying times of the gastrointestinal tract. A total of 15 healthy box turtles were recruited for this prospective, anatomic, reference interval study. Three‐view radiographic series (vertical beam dorsoventral, horizontal beam latero‐lateral, and horizontal beam rostrocaudal views) were acquired prior to contrast administration, and following contrast administration at 0, 20, 40, 60, and 90 min, 2, 4, 8, 12, and 24 h post administration, and every 24 h thereafter until all contrast was eliminated (15 mL/kg barium sulfate diluted to 30% weight per volume was administered via orogastric gavage). Vertical beam dorsoventral and horizontal beam latero‐lateral views were of excellent quality to identify gastrointestinal structures. The horizontal beam rostrocaudal view immediately postcontrast administration provided gastric and pyloric identification but had lesser diagnostic use at later time points due to anatomical superimposition. The gastrointestinal tract was composed of a tubular stomach, a pyloric sphincter near midline, a duodenum with a cranial flexure in the right cranial coelomic cavity, small intestines within the right coelom, a small cecal bulb, and a transverse and descending colon. Contrast media entered the large intestine by 24 h in all turtles, and a pyloro‐colic indentation was noted at the proximal descending colon. The large intestinal emptying was highly variable due to the interindividual variability of contrast sequestration within the cecal bulb. Findings from the current study serve as a reference on the gastrointestinal anatomy, transit, and emptying times in healthy eastern box turtles; and introduce a novel, horizontal beam, rostrocaudal view for gastrointestinal contrast studies in chelonians.  相似文献   

14.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage a wide variety of conditions in horses, including management of colic. Flunixin meglumine is by far the most commonly used drug in the control of colic pain and inflammation and has become a go-to for not only veterinarians but also horse-owners and nonmedical equine professionals. NSAID use, however, has always been controversial in critical cases due to a high risk of adverse effects associated with their potent cyclo-oxygenase (COX) inhibition. There are two important COX isoenzymes: COX-1 is generally beneficial for normal renal and gastrointestinal functions and COX-2 is associated with the pain and inflammation of disease. Newer selective NSAIDs can target COX-2-driven pathology while sparing important COX-1-driven physiology, which is of critical importance in horses with severe gastrointestinal disease. Emerging research suggests that firocoxib, a COX-2-selective NSAID labelled for use in horses, may be preferable for use in colic cases in spite of the decades-long dogma that flunixin saves lives.  相似文献   

15.
Cyclooxygenase (COX) inhibitors and the intestine   总被引：1，自引：0，他引：1  
Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.  相似文献   

16.
A healthy adult, intact female keeled box turtle (Cuora mouhotii) was found to have a marked heterophilic leukocytosis using normal hematologic parameters established for the eastern box turtle (Terrapene carolina carolina), a related chelonian species. This animal was monitored with serial complete blood counts (CBCs) over the next 15 years despite remaining asymptomatic for an infectious condition. Retrospective CBC data were compiled from 38 presumably healthy keeled box turtles to establish hematologic values for comparison in this species. Using this species-specific data, over the 15-year period, the female keeled box turtle had two times where the white blood cell (WBC) count was greater than 2 standard deviations (SD) above the mean, six times where the WBC count was greater than 1 SD above the mean, six times where the PCV was greater than 2 SD above the mean, and eight times where the PCV was greater than 1 SD above the mean. Infection and inflammation are the most common causes of leukocytosis in reptiles; however, given the clinical presentation of this patient, it was postulated that these clinicopathologic changes could be secondary to a stress response. Establishing reference intervals and understanding how stress impacts CBC parameters are important for evaluating the health status of keeled box turtles kept in captivity and for assessing the effects of environmental changes on the health status of wild populations of this endangered chelonian species.  相似文献   

17.
Cyclooxygenase (COX) performs the critical initial reaction in the arachidonic metabolic cascade, leading to formation of proinflammatory prostaglandins, thromboxanes, and prostacyclins. The discovery of a second COX isoform (COX-2) associated with inflammation led to agents that selectively inhibit COX-2. Cyclooxygenase-2 inhibitors are also being developed for canine applications. To assess the compound potency on canine enzymes, canine COX-1 and COX-2 were cloned, expressed, and purified. Cyclooxygenase-1 was cloned from a canine kidney complementary DNA (cDNA) library, with 96 % sequence homology to human COX-1. Cyclooxygenase-2 was cloned from canine kidney and lipopolysaccharide-stimulated macrophage cDNA libraries, with a 93 % sequence homology to human COX-2. The arachidonic acid Michaelis constants for canine COX-1 and COX-2 were 4.8 and 6.6 micrometer, respectively, compared with 9.6 and 10.2 micrometer for ovine. Inhibition results indicated that, for all compounds tested, there was no significant difference between potencies determined for canine enzymes and those for human enzymes.  相似文献   

18.
Bovine urinary bladder tumors occur frequently in animals suffering from chronic enzootic hematuria because of prolonged ingestion of bracken fern (Pteridium spp.). Cyclooxygenase (COX) genes (COX-1 and COX-2) are known to be involved in the carcinogenesis of human and some animal urothelial tumors. The aim of the present study was to investigate COX-1 and COX-2 expression by immunohistochemical methods in 20 bovine urothelial carcinomas collected at public slaughterhouses from cows that had been suffering from chronic enzootic hematuria. COX-1 immunostaining was identified intracytoplasmically in normal urothelium and in 15 of 20 neoplastic specimens. COX-1 immunosignal in the tumor cells was either absent or weak. COX-2 was also expressed intracytoplasmically in 17 of 20 urothelial carcinomas. Moderate to intense COX-2 labeling was detected in both noninvasive and invasive urothelial carcinomas. Coexpression of both enzyme isoforms was also revealed by confocal laser scanning microscopic investigations. This study indicates that COX-2 is overexpressed in naturally occurring urothelial carcinomas of cows.  相似文献   

19.
本研究旨在克隆猪CPB2基因的不同可变剪接体，预测对应蛋白的功能特性以及研究不同转录本表达特性。以健康状态和体重相同的3头12月龄巴马小型猪为试验动物，通过RT-PCR技术及基因平末端克隆技术扩增猪CPB2基因的CDS区及部分非编码区，利用生物信息学工具预测CPB2编码蛋白的基本生物学特征，利用RT-PCR技术检测CPB2基因在肝、心、肾、皮下脂肪、肠系膜脂肪、股二头肌和背最长肌中的表达特征。以实验室制备的代谢性疾病易感猪为试验动物，利用qRT-PCR技术检测CPB2基因在富营养饮食效应下肝中的表达特征。结果表明，本研究成功克隆出猪CPB2基因的3种可变剪接体（CPB2-1、CPB2-2和CPB2-3），其中CPB2-1与NCBI序列XM_001929146.4相同，CPB2-2和CPB2-3为新发现转录本。与CPB2-1相比，CPB2-2和CPB2-3发生了5'端可变剪接（alternative 5'splice site，A5SS）事件；CPB2-1编码423个氨基酸的酸性不稳定性蛋白，CPB2-2和CPB2-3编码同种281个氨基酸的碱性不稳定性蛋白；与CPB2-1相比，CPB2-2和CPB2-3缺少信号肽和激活肽，但具有相同羧肽酶活性结构域；CPB2基因3种转录本仅在肝和肾中表达，其他组织无表达；在富营养饮食诱导的代谢性疾病易感猪的肝中，CPB2-1（P<0.01）和CPB2-2（P<0.01）显著降低，CPB2-3未显著降低（P=0.14）。综上，本研究成功在肝中克隆了猪CPB2的3种可变剪接体，推测CPB2-1是行使纤溶与凝血等生理功能的正常转录本；新发现转录本CPB2-2和CPB2-3被留在肝和肾中可能具有羧肽酶活性和重要生理学功能；CPB2基因可能与代谢相关的慢性肝病存在一定联系。  相似文献   

20.
OBJECTIVE: To develop and validate in cats suitable in vitro assays for screening and ranking nonsteroidal antiinflammatory drugs (NSAIDs) on the basis of their inhibitory potencies for cyclooxygenase (COX)-1 and COX-2. ANIMALS: 10 cats. PROCEDURE: COX-1 and COX-2 activities in heparinized whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. For the COX-2 assay, blood was pretreated with aspirin. The COX-1 and COX-2 assays were standardized, such that time courses of incubation with the test compounds and conditions of COX expression were as similar as possible in the 2 assays. Inhibition of thromboxane B2 production, measured by use of a radioimmunoassay, was taken as a marker of COX-1 and COX-2 activities. These assays were used to test 10 to 12 concentrations of a COX-1 selective drug (SC-560) and of 2 NSAIDs currently used in feline practice, meloxicam and carprofen. Selectivities of these drugs were compared by use of classic 50% and 80% inhibitory concentration (ie, IC50 and IC80) ratios but also with alternative indices that are more clinically relevant. RESULTS: These assay conditions provide a convenient and robust method for the determination of NSAID selectivity. The S(+) enantiomeric form of carprofen was found to be COX-2 selective in cats, but meloxicam was only slightly preferential for this isoenzyme. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro pharmacodynamic and in vivo pharmacokinetic data predict that the COX-2 selectivity of both drugs for cats will be limited when used at the recommended doses. This study provides new approaches to the selection of COX inhibitors for subsequent clinical testing.  相似文献   

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