Role of paraoxonase-1 as a diagnostic marker for feline infectious peritonitis.

Feline infectious peritonitis (FIP) is characterised by the presence of systemic inflammation accompanied by oxidative stress. Paraoxonase-1 (PON-1) is a negative acute phase reactant produced by the liver. A paraoxon-based method has been validated to measure PON-1 activity in feline serum. The aim of this study was to investigate the usefulness of PON-1 activity as a biomarker to discriminate FIP from other diseases with similar clinical signs. Of 159 cats enrolled, 71 were healthy, 34 had FIP and 54 had another disease but presented with clinical signs that could be consistent with FIP. PON-1 activity was lower (P <0.0001) in cats with FIP (median, 26.55 U/L; range, 5.40-78.20 U/L) compared to healthy (median, 87.5 U/L; range, 46.60-215.50 U/L) and Non-FIP Sick group cats (median, 57.90 U/L; range, 3.80-122.60 U/L). Two receiver operating characteristic curves were used to determine the thresholds that maximised the performance of PON-1 activity in predicting FIP both from a screening and diagnostic point of view. A threshold of 78.30 U/L yielded a sensitivity of 100%, a specificity of 50.4%, and a negative likelihood ratio of 0.00 (screening curve). While a threshold of 24.90 U/L maximised specificity (94.4%), had a sensitivity of 44.1%, and increased the likelihood ratio to 7.94, making PON-1 activity a good confirmatory test for FIP (diagnostic curve). Using these thresholds, serum PON-1 activity showed good diagnostic performance in discriminating FIP affected cats from cats with other inflammatory conditions.

Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.

Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis-transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis-transisomerase active sites of Cyps might be required for FCoV replication.

Electrophoretic fractionation of creatine kinase isoenzymes and macroenzymes in clinically healthy dogs and cats and preliminary evaluation in central neurologic disease.

BACKGROUND: Information about the electrophoretic distribution of CK-MM, CK-MB, and CK-BB, serum creatine kinase (CK) isoenzymes that are indicators of skeletal muscle, cardiac muscle, and brain lesions, respectively, and CK macroenzymes (macro-CK1 and macro-CK2) in dogs and cats with and without central neurologic disease is scant and equivocal. OBJECTIVES: The objectives of this study were to describe the electrophoretic distribution of CK isoenzymes and macroenzymes in healthy dogs and cats and to provide a preliminary assessment of the utility of CK enzymatic electrophoresis in dogs and cats with central neurologic disease. METHODS: Electrophoretic separation of serum CK isoenzymes and macroenzymes was performed on freeze-thawed serum samples from 20 healthy dogs and 3 dogs with central neurologic disease and from 14 healthy cats and 6 cats with neurologic feline infectious peritonitis (FIP). Electrophoretic separation was also performed on supernatants of homogenized brain, skeletal muscle, and cardiac muscle from both species, to assess the tissue distribution of isoenyzmes in dogs and cats. RESULTS: CK-MM was the predominant isoenzyme in the serum of healthy dogs and cats, followed by macro-CK2 and CK-BB in dogs and by both macroenzymes in cats. In dogs, CK-MB was essentially absent from both serum and homogenized hearts. CK-BB increased in dogs with neurologic disease. In cats, CK-BB was essentially absent from serum, but was present in brain homogenates. Two of 6 cats with FIP had increased macro-CK1 and increased CK-BB activity. CONCLUSIONS: This study identified the electophoretic distribution of CK isoenzymes and macroenzymes of dogs and cats and provided encouraging data about the possible use of CK-BB as a biomarker for canine neurologic disorders, but not for FIP.

Validation of the determination of the activity of adenosine deaminase in the body effusions of cats.

In order to identify parameters differentiating exudative from transudative effusions, it was postulated that the activity of adenosine deaminase (AD) (EC 3.5.4.4) might be highly correlated with granulomatous inflammatory processes of the serosa, and the activity of the enzyme in body effusions and serum from cats was examined. The method of Slaats et al (1985) for the determination of the enzyme was evaluated by using an Hitachi 705 autoanalyser, and its activity was measured in body cavity effusions of 174 cats. The activity of AD was high in effusions from cats with infectious serositis and bacterial or feline infectious peritonitis (FIP). In cases of FIP the activity of AD was very significantly different from all other cases of thoracic (P = 0.004) and abdominal (P < 0.0001) effusions. The determination of AD in the serum of cats did not contribute to the aetiological differentiation of hydrops. The increases in the activity of AD appeared to originate from the body effusion, because the ratio of the activity of the enzyme in the effusion to its activity in serum was relatively high in cases of FIP.