In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Methicillin resistant Staphylococcus aureus (MRSA) infection in a dog in the Netherlands

In the Netherlands, methicillin resistant Staphylococcus aureus (MRSA) are regularly isolated from humans. We present the first isolation of MRSA from animal origin in the Netherlands. A coagulase positive staphylococcus was cultured from an infected wound in a Dutch dog that recently underwent surgery abroad. The staphylococcus was resistant to methicillin, ampicillin, amoxycillin + clavulanic acid, cephalexin, erythromycin, lincomycin, tetracycline, gentamicin and enrofloxacin. It was identified as S. aureus by fermentation of mannitol and Martineau-PCR. The presence of mecA was confirmed by PCR.     

世界猪病的发展与演变

1 疾病是生态的和进化的动态过程 任何疾病都是某些相互作用持续进行的结果,这种相互作用在传统上一直被称为“病原-宿主-环境”三者之间的相互作用,这种概念已经相当过时。甚至较新的病因网络观点仍然有其局限性,因为它仅仅考虑到危害因素,而疾病的发展还包括时间和空间上的因素。我们只注意捕捉疾病的个别图像,这种思维方式往往左右了我们对疾病的考虑。动物死亡之后,病理学家看到的只是疾病的“静态照片”;临床专家看到的只是主要时期的     

Use of the ARC/INFO GIS to study the distribution of Lyme disease ticks in an Illinois county

Lyme disease is a bacterial disease of humans and domestic animals transmitted primarily through the bite of the deer tick, Ixodes dammini. Using the ARC/INFO geographic information system (GIS), the distribution of tick vectors can be associated simultaneously with a large number of environmental, biological and demographic factors. The Illinois GIS was used to study the associations of soil type, potential vegetation cover and distance from waterways with tick distributions, and to compare the dispersion patterns of tick-infested and uninfested deer in one northwestern Illinois county. Tick presence was associated with sandy soils, wooded vegetation, and proximity to rivers. Infested deer were clustered around an endemic focus I. dammini, while uninfested deer showed no such clustering. Changes in the spatial distribution of ticks over two years and likely sites for further establishment of ticks were also studied.     

Ten-year study comparing enzyme-linked immunosorbent assay with the immunofluorescent antibody test for detection of feline leukemia virus infection in cats.

Immunodetection tests for feline retroviruses are powerful tools used in modern veterinary practice. Veterinarians must fully understand the characteristics--strengths and weaknesses--of the FeLV tests so that the information gained from them can be used properly. Any FeLV ELISA or immunofluorescent antibody (IFA) test is a method for detection of FeLV infection (the virus) and is not a diagnostic test for leukemia or other feline disease. From previous studies, it was determined that the most accurate test for detection of persistent FeLV infection is the IFA test, which detects FeLV antigens in cytoplasm of leukocytes in the blood of infected cats. In the study reported here, 1,142,600 FeLV IFA tests were performed between June 1972 and December 1990. During this period 19.8% of the IFA test results were positive and 78% were negative. Evaluation was not possible for the remaining 2.2% of the tests because of lack of enough leukocytes in the smears to evaluate, or nonspecific staining reactions. In 1979, 7 years after introduction of the IFA test, in-hospital FeLV ELISA were introduced, which enabled veterinarians to test for FeLV in their hospitals. Ever since that time, continual discrepancies have been reported between results of FeLV ELISA and IFA tests, particularly between positive ELISA results and their IFA test confirmation. A 10-year comparison was made between practitioner-performed in-hospital FeLV ELISA (n = 20, 240 tests) results and FeLV IFA test performed by a commercial laboratory. All samples tested by ELISA were submitted (for confirmation of results) by veterinarians from the United States, Canada, Europe, Japan, and Australia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic responses to ammonium acetate infusion in exercising horses.

The relationship between elevated plasma ammonia (NH3) levels, fatigue development and muscle metabolism were examined in horses during a submaximal fatigue test. Eight Quarter Horse mares were intravenously infused prior to exercise with either sodium acetate (control) or ammonium acetate (AMINF), and exercised to fatigue on an 11% grade treadmill, carrying 27 kg of lead. Time to fatigue was not different (P greater than 0.05) between groups. Intramuscular NH3 and lactate increased (P less than 0.001) during exercise; however, the treatment did not (P greater than 0.05) affect either. A treatment by exercise interaction (P less than 0.01) occurred for plasma NH3. The reciprocal relationship between changes in plasma and intramuscular alanine (ala) and glutamate (glu) indicated activation of the glucose-alanine cycle. Plasma glutamine (gln) increased (P less than 0.001) during exercise; however intramuscular gln was not (P greater than 0.05) altered. The excretion of urea-N was depressed as a result of exercise while the orotic acid/creatinine ratio did not (P greater than 0.05) change. The amino acids and urinary metabolites were not (P greater than 0.05) affected by treatment. These results did not show any metabolic evidence for a role of increased plasma NH3 levels in fatigue development. However this study did provide insight into other aspects of nitrogen metabolism during exercise in the horse.     

Serum liver enzyme and histopathologic changes in calves with chronic and chronic-delayed Senecio jacobaea toxicosis.

Progressive changes in serum enzyme activity and liver histologic features were monitored in calves fed tansy ragwort (Senecio jacobaea)-contaminated pellets. The experiments were designed to simulate natural intoxicant ingestion conditions in relationship to the dose and duration of exposure to the toxic plant to correlate early laboratory diagnostic changes with the natural progression of the disease, thereby facilitating early diagnosis and intervention by veterinary clinicians. Eight calves were fed tansy ragwort and 4 additional calves served as controls. In group 1, 4 calves were continuously fed dried tansy ragwort mixed in a pelleted feed at a 5% concentration by dry weight until terminal liver disease developed. Serum liver enzyme (alkaline phosphatase, glutamate dehydrogenase, and gamma-glutamyltransferase) activities were monitored at weekly intervals in these calves and in the 2 controls. In group 2, 4 calves were fed the same contaminated feed for only 60 days, with return to normal feed for the duration of the trial. Two additional calves served as controls. Their liver enzyme activities were monitored every other week in conjunction with percutaneous liver biopsies. All 8 calves fed tansy ragwort-contaminated pellets developed terminal hepatopathy in either a chronic pattern (n = 6) or a chronic-delayed pattern (n = 2), with the onset of a moribund state or sudden death at 11 to 17 weeks and 27 to 51 weeks, respectively. The calves were euthanatized when classic terminal signs of hepatic encephalopathy first became evident. The clinicopathologic patterns of chronic and chronic-delayed toxicoses were typical of over 5,000 cases of field tansy toxicosis diagnosed at the diagnostic laboratory. Serum glutamate dehydrogenase was the first enzyme to increase in most animals, with a short-term increase to peak values followed by a rapid return to normal. This enzyme change was followed by increases in alkaline phosphatase and gamma-glutamyltransferase. Serum enzyme changes preceded development of recognizable histologic lesions. Vacuolar changes in hepatocyte nuclei, biliary hyperplasia, and fibrosis sequentially developed in liver biopsy specimens from each animal, whereas megalocytosis was not a predominant feature until necropsy. On the basis of our findings, we suggest that the optimal tests for diagnosis of pyrrolizidine alkaloid intoxication should consist of liver biopsy and determination of concurrent serum liver-enzyme activities.     

Further studies on the antinociceptive activity and respiratory effects of buprenorphine in sheep

The thermal and mechanical analgesic profile of buprenorphine at a dose rate of 1.5 micrograms/kg i.v. was investigated in five sheep. This dose produced significant analgesia for 40 min against the thermal stimulus, but no mechanical antinociception. A higher dose rate of 12 micrograms/kg also failed to produce antinociception to a mechanical stimulus. In addition, the effect of the drug (6 micrograms/kg) on respiratory gas tensions was determined and no significant changes were observed.     

Light and electron microscopic observations of a segmented filamentous bacterium attached to the mucosa of the terminal ileum of pigs.

Segmented filamentous bacteria were seen attached to apical villous enterocytes of the terminal ileum in 15 of 2,766 live pigs submitted for necropsy over a 6-year period. Infected pigs ranged in age from 2 to 13 weeks. All pigs except 2, however, were greater than 4 weeks old and had been weaned. All infected pigs came from conventional commercial herds with intensive, all-indoor, confinement rearing management systems. The bacteria were gram negative or gram variable and were not associated with any clinical disease. Bacteria were more commonly attached to epithelium on the dome villi in the ileum. Electron microscopic examination revealed organisms composed of a cranial segment with a nipple-like appendage and several other segments making up elongated filaments of various lengths. Each filament was divided into segments by transverse septa. The nipple-like appendage served as an attachment apparatus by indenting the enterocyte surface without physically penetrating it. Occasionally, the colonizing bacterium was itself colonized by small rod-shaped bacteria that completely surrounded the filament.     

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.