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1.
Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5-aminosalicylic acid (5-ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by high-performance liquid chromatography methods. Evaluation of the plasma pharmacokinetics revealed a rapid, but low extent of absorption of OLZ (peak concentrations around 1 microg/mL at 0.5-1.5 h), and a delayed minimal absorption of 5-ASA (concentrations < 0.2 microg/mL, at 11-35 h), which is immediately metabolized to Ac-5-ASA. As indicators of the local availability in the colon, high faecal water concentrations of 5-ASA and Ac-5-ASA (mean C(max) about 300 and 130 microg/mL, respectively), but only traces of OLZ were found in faeces excreted 18-50 h after dosing. Of the administered OLZ dose 26% could be recovered from faeces, almost completely as 5-ASA and Ac-5-ASA. Routine clinical examination of the horses and assay of standard haematological and serum chemistry parameters before and after OLZ administration confirmed that a single dosage of 30 mg/kg was well tolerated. To estimate the systemic availability of 5-ASA liberated from OLZ, 5-ASA was administered i.v. at a dosage of 1.5 mg/kg to four horses and plasma concentrations of 5-ASA and Ac-5-ASA were determined. The pharmacokinetic evaluation showed a very low bioavailability of 2.4% for 5-ASA, released from orally administered OLZ. Furthermore, in an in vitro experiment, the metabolic transformation of 5-ASA to Ac-5-ASA mediated by bacteria in the caecal content of horses was determined at 38 degrees C for 31 h and compared with the metabolism data of the in vivo study. The markedly lower degree of acetylation in vitro supports the assumption that biotransformation of 5-ASA in vivo occurs not only by colonic bacteria, but also at other sites.  相似文献   
2.
In recurrent airway obstruction (RAO) or heaves, bronchospasm has been attributed to enhanced cholinergic activity. However, the expression and function of muscarinic acetylcholine receptors (mAChR) and their signaling components are not yet known. Thus, we examined the expression, subtype distribution and postreceptor signaling pathways of mAChR in the peripheral lung, bronchial and tracheal epithelia with the underlying smooth muscle from nine horses with RAO and 11 healthy control horses. In RAO horses, no significant segment-dependent alteration in mAChR density and subtype distribution (assessed by [N-methyl-3H]-scopolamine binding; ([3H]-NMS)), was found, except a trend in receptor down-regulation in some peripheral parts of the lung. The total number of high mAChR binding sites (assessed by carbachol-displacement experiments in the presence or absence of guanosine 5'-triphosphate) was not changed in RAO, suggesting that the functional coupling of mAChR to the corresponding G-proteins is intact. The M2-mediated inhibition of adenylate cyclase (AC) as well as the M3-receptor-G(q/11)-phospholipase C (PLC) activity was not different between RAO and control airway tissues. In conclusion, in equine RAO airways, mAChR expression and function were not altered, and thus appear not to account for the enhanced cholinergic activity in RAO.  相似文献   
3.
Blood cell morphology and count are not uniform across species. Recently, between‐species comparisons revealed that the size of red blood cells is associated with body size in some lizard taxa, and this finding was interpreted in the context of the metabolic theory. In the present study, we examined the numbers and the size of blood cells in 2 species of monitor lizards, the mangrove‐dwelling monitor (Varanus indicus) and the savannah monitor (V. exanthematicus), and we compared these traits in individuals of different body size. The results revealed that during the course of ontogeny, the size of red blood cells increases with body mass. Because the mass‐specific metabolic rate decreases with body size and the cell volume‐to‐surface ratio decreases with the cell size, changes in the erythrocyte size might be the result of oxygen transport adjustment.  相似文献   
4.
Infectious Ovine Keratoconjunctivitis (IOK) is a contagious ocular disease of sheep. A range of organisms have been observed as the aetiological agents of IOK. In this study, the presence of chlamydial pathogens (C. pecorum, C. abortus, C. psittaci) in conjunctival swabs was tested for. The swabs were collected from sheep with varying grades of IOK in an Australian pre‐export feedlot. The sheep had been rejected from a shipment because of the eye disease. The relative contribution of chlamydial pathogens to IOK and the rejection of animals was evaluated. In total, 149 conjunctival swabs were taken from rejected sheep (IOK Grades 1 to 6; n = 126) as well as those with healthy eyes (Grade 0; n = 23). Screening for chlamydial pathogens was done using species–specific qPCR assays. Chlamydial DNA was detected in 35.6% (53/149) of conjunctival samples. C. pecorum was the most predominant species with an overall prevalence of 28.9% (43/149). C. psittaci prevalence was 6.7% (10/149). Both organisms were detected in healthy as well as IOK‐affected eyes. All swabs tested negative for C. abortus. The results from this study demonstrate that Chlamydia spp can be readily detected in sheep presenting with IOK. The zoonotic C. abortus was not detected in any of the samples in this study, providing further evidence to the suggestion that this pathogen remains absent from Australia. Although the exact contribution of Chlamydia spp in the IOK pathogenesis is unclear, such studies are anticipated to be of benefit to Australian domestic and live export production systems.  相似文献   
5.
Because of the importance of reproduction in stock breeding systems, it is necessary to find selection criteria that increase reproductive efficiency. The aim of this study was to estimate genetic parameters for the probability of conception on first service (PROB) in Murrah heifers, and its association with other traits of economic interest [age at first calving (AFC), service period, calving interval and milk yield at 270 days], with the purpose of evaluating their use as selection criteria. Reproductive information and first lactation records of 1200 Murrah heifers were used to perform two‐trait analyses between PROB and the other characteristics. Bayesian inference was used to estimate the variance components, considering PROB as threshold and the other as linear factors. The results demonstrate that this trait has heritability of 0.15, indicating the possibility of a genetic gain by using it for selection. With respect to the genetic correlation estimates, the only high‐magnitude association was with AFC (?0.899), which is the current criterion indicating sexual precocity of females. In the light of the parameters estimated, the first‐service pregnancy rate is an alternative for indication of sexual precocity, although presenting a smaller genetic gain than the current standard AFC. Nevertheless, additional research should be conducted regarding this trait to assess the economic importance of its use in dairy buffalo production systems.  相似文献   
6.
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7.
The objective of this study was to define the patterns of organogenesis and foetal haemodynamics during the normal gestation of healthy agoutis (Dasyprocta prymnolopha) kept in captivity. Thirty pregnant agoutis that ranged in size from small to medium and weighed between 2.5 and 3 kg underwent B‐mode and Doppler ultrasonography for the biometric evaluation of the foetal organs. The foetal aortic blood flow proved to be predominantly systolic, and the measured flow velocity was 78.89 ± 2.95 cm/s, with a maximum pressure gradient of 2.12 ± 0.27 mmHg. The liver was characterized by its large volume, occupying the entire cranial aspect of the abdominal cavity, and it was associated cranially with the diaphragm and caudally with the stomach. The flow velocity in the portal vein was estimated to equal 12.17 ± 2.37 cm/s, with a resistivity index of 0.82 ± 0.05. The gallbladder was centrally located and protruded cranially towards the diaphragm. The spleen was visualized as an elongated structure with tapered cranial and caudal extremities, and the foetal kidneys were visualized bilaterally in the retroperitoneal region, with the right kidney positioned slightly more cranially than the left. The morphological characterization and hemodynamic analysis of the foetal organs of black‐rumped agoutis via B‐mode and Doppler ultrasonography allow determination of the vascular network and of reference values for the blood flow required for perfusing the anatomical elements essential for maintaining the viability of foetuses at different gestational ages.  相似文献   
8.
Intestinal wall thickness is neither a specific nor sensitive ultrasound parameter for detecting intestinal inflammation. We hypothesize that mucosal echogenicity, lymphadenomegaly, and secondary findings of the gastrointestinal tract would be more sensitive and specific markers for detecting and differentiating causes of chronic inflammatory bowel disease in dogs. Fifty-six client-owned dogs with chronic diarrhea and 10 control dogs were examined with two-dimensional, gray-scale ultrasound (time 0, 4, and 10 weeks post therapy) and small intestinal mucosal biopsies were performed at the 0- and 4-week time points. The clinical activity was assessed at each time point using the canine inflammatory bowel disease activity index (CIBDAI). Fifty-one dogs had inflammatory infiltration of the duodenal mucosa and were divided into three groups, food-responsive disease, idiopathic inflammatory bowel disease, and protein-losing enteropathy, based on their response to the different treatments and histology. Two different patterns of increased echogenicity of the mucosa were detected: hyperechoic speckles and hyperechoic striations. A normal, hypoechoic bowel mucosa in dogs with chronic diarrhea had a sensitivity of 80% and a specificity of 81% for the diagnosis of food-responsive disease. Hyperechoic striations had a sensitivity of 75% and a specificity of 96% for dogs with protein-losing enteropathy. Hyperechoic speckles were non-specific for diagnosing inflammatory bowel disease. There was a significant relationship between ultrasound score and CIBDAI at t0, but not following therapy. Mucosal echogenicity may be a better parameter for detecting inflammatory bowel disease than bowel wall thickness in dogs with chronic diarrhea.  相似文献   
9.
In 12 healthy horses, the effects of the beta2-agonist clenbuterol and the glucocorticoid dexamethasone on the lymphocyte beta2-adrenoceptor density and affinity (determined by (-)-[125I]-iodocyanopindolol binding) as well as its responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 micromol/l (-)-isoprenaline) were studied. Clenbuterol treatment, 2 x 0.8 microg/kg/day i.v. for 12 days, decreased significantly ICYP binding sites by approximately 30-40%; concomitantly, lymphocyte cAMP response to (-)-isoprenaline was reduced. After withdrawal of clenbuterol, beta2-adrenoceptor density and responsiveness gradually increased, reaching predrug levels after 4 days. The effects of dexamethasone on clenbuterol-induced desensitisation were further investigated. Administration of dexamethasone (1 x 0.1 mg/kg/day, i.v. for 5 days) immediately after clenbuterol withdrawal accelerated beta2-adrenoceptor recovery: only 24 h after administration dexamethasone restored the number of binding sites and cAMP response to (-)-isoprenaline to levels statistically indistinguishable from values before clenbuterol treatment. Three days after dexamethasone administration, lymphocyte beta2-adrenoceptors were further increased about 2-fold the pretreatment values, and this increase declined gradually after dexamethasone withdrawal, reaching baseline values after 4 days. Furthermore, in groups exposed simultaneously to both drugs, dexamethasone completely prevented clenbuterol-induced decrease in lymphocyte beta2-adrenergic receptor density and responsiveness. No significant change was observed in the dissociation constant for ICYP in any of the situations. We conclude that dexamethasone (glucocorticoids) can reverse and prevent Clenbuterol-induced desensitisation (down-regulation) of the lymphocyte beta2-adrenoceptors and therefore, a combined therapy with clenbuterol and dexamethasone may be potentially beneficial in horses suffering from chronic obstructive pulmonary disease (COPD).  相似文献   
10.
Doping in performance horses is defined as the "illegal application of any substance, except normal diet, that might modify the natural and present capacities of the horse at the time of the race." The prohibition of doping is mainly based on the protection of animals. Doping can be performed with various aims: "doping to win" can be regarded as the classical method by mobilization of overphysiological capacities. Such positive doping may be classified as an acute form using psychomotoric stimulants, as a chronic form using anabolic hormones, and as a paradoxical form using small doses of neuroleptics or tranquilizers in excitable horses. In larger doses these sedatives are acting for "doping to loose" in a more subtle manner as compared to hypnotics. According to the doping regulations there is no difference between therapy and doping at the time of the race. Thus at the race all medications to restore normal performance have to be regarded as doping. This fact especially concerns the therapy of lamenesses with non-steroidal antiinflammatory drugs or local anesthetics. A particular problem is "inadvertent" doping due to unknown side effects, combinations of drugs, galenic supplements or food additives. Accidental doping may further be caused by the unawareness of elimination times. At the moment no exact withdrawing times can be defined due to the manifold interindividual variations at different levels of the pharmacokinetics. As a border-line case of doping the application of endogenous substances, like electrolytes or glucose, may be regarded. Though their parenteral application is prohibited prior to the race, only bicarbonate or "blood doping" may be considered to be effective as positive doping. Special doping methods are the use of "masking" substances or diuretics in order to make more difficult the detection of illegal drugs as well as physical doping procedures which are often hardly to define and which thus are only in part included in the doping regulations.  相似文献   
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