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G E Lees P F Suter G C Johnson 《Journal of the American Veterinary Medical Association》1978,172(6):690-696
Acute pancreatitis and cardiac disease were diagnosed in a dog with pulmonary edema. The early clinical course and initial thoracic radiographs suggested that the pulmonary edema was noncardiogenic. The late clinical course was complicated by heart failure. The dog died, and a necropsy was performed. Histologically, an acute, severe capillary-alveolar membrane lesion was found in the lungs. Review of the human medical literature indicated that respiratory complications, including pulmonary edema, are commonly recognized in people with acute pancreatitis. Furthermore, in acute pancreatitis of human beings, the existence of specific mechanisms of pulmonary injury is suspected. Retrospective consideration of this case suggested that the initial pulmonary edema was induced by acute pancreatitis. 相似文献
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Wilmink JM Veenman JN van den Boom R Rutten VP Niewold TA Broekhuisen-Davies JM Lees R Armstrong S van Weeren PR Barneveld A 《Equine veterinary journal》2003,35(6):561-569
REASONS FOR PERFORMING STUDY: Wound healing proceeds faster in ponies than in horses and complications during healing, such as wound infection, occur less frequently in ponies. Earlier studies suggested that this difference might be related to differences in the initial post traumatic inflammatory response. HYPOTHESIS: That polymorphonuclear leucocyte (PMN) function and profiles of humoral factors in local inflammatory processes are different in horses and ponies. METHODS: PMNs were isolated from venous blood of horses and ponies. Chemotaxis and reactive oxygen species (ROS) production was determined. Tissue cages were implanted in limbs and necks of horses and ponies and injected with carrageenan and, 3 weeks later, with LPS. In sequential samples of inflammatory exudate, the numbers of macrophages and PMNs and the production of PGE2, TNFalpha, IL-1, IL-6 and chemoattractants were determined. RESULTS: In vitro ROS production of PMNs was significantly higher in ponies than in horses, whereas in vitro PMN chemotaxis was significantly lower in ponies. In the tissue cages for both stimuli, the production of IL-1 and chemoattractants was significantly higher in ponies than in horses and remained so towards the end of the observation period in ponies. CONCLUSIONS: This study demonstrated a higher production of various inflammatory mediators by pony leucocytes. Despite the lower in vitro chemotaxis of pony PMNs, this higher in vivo production resulted in a stronger initial inflammatory response in ponies, as has been reported in studies on wound healing, through the attraction of leucocytes and triggering of the production of other cytokines. A stronger initial inflammation may promote healing by more rapid elemination of contaminants and earlier transition to repair. POTENTIAL RELEVANCE: Modulation of the initial inflammatory response might therefore be a valid option for therapeutic intervention in cases of problematic wound healing. Further, the intraspecies differences in leucocyte function may have an impact on many fields in equine medicine. 相似文献
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Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum,exudate and transudate 总被引:5,自引:0,他引:5
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration-time curve (AUC) and elimination half-life (t(1/2)el) values were 9.99 and 10.11 microg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 microg h/mL after intravenous and 8.84, 8.53 and 8.52 microg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 microg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 microg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms. 相似文献
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The efficacy of eight benzimidazole anthelmintics has been examined against Trichostrongylus colubriformis in gerbils and Nippostrongylus brasiliensis in rats, when the parasites were entering into the fourth and final moult. The dose--response slopes obtained from the data for both host--parasite systems did not deviate significantly from a non-parallel model, and were used for relative potency determinations. The T. colubriformis assay ranked the benzimidazoles in order of potency as follows: albendazole, oxfendazole, fenbendazole, cambendazole, mebendazole, oxibendazole, parbendazole and thiabendazole. This compares favourably with the expected relative efficacies against trichostrongyles in sheep. N. brasiliensis was found to be far less useful in this respect. All compounds tested, with the exception of thiabendazole, were highly effective against both parasites. The T. colubriformis/gerbil assay could be a very useful tool for preliminary in vivo evaluation and possibly in the early selective optimisation of chemical series. 相似文献
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L. Pelligand J. N. King V. Hormazabal P. L. Toutain J. Elliott P. Lees 《Journal of veterinary pharmacology and therapeutics》2014,37(4):354-366
Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B2 concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E2 concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE2 concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB2 between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC50COX‐1/IC50COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood. 相似文献
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