Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease.

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P less than or equal to 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.

OBJECTIVE To determine the feasibility of radiographic measurement of liver area in small-breed dogs and to assess correlations between CT liver volume measurements (reference standard) and radiographic liver size measurements. ANIMALS 107 small-breed dogs (body weight, ≤ 10 kg) that had previously undergone orthogonal thoracic and abdominal radiography and abdominal CT. PROCEDURES In a retrospective study design, dogs were allocated to groups (normal liver [n = 36], microhepatia [34], and hepatomegaly [37]) on the basis of radiographic liver size and clinicopathologic findings. Radiographic liver area (RLA) was automatically calculated from archived radiographic images by free-hand outlining of the liver margins by use of DICOM viewer software, and other standard radiographic measurements were performed. Liver volume was measured on CT images. Intraoperator repeatability of RLA and CT measurements was assessed (duplicate measurements 2 weeks apart). To control for various breed conformations, radiographic values were normalized to body weight and T11 area. RESULTS Mean ± SD ratios of RLA to T11 area and RLA to body weight for dogs with normal livers were 32.7 ± 6.2 and 7.0 ± 1.4, respectively. Excellent intraobserver agreement was observed in RLA measurements within groups (intraclass correlation coefficients, 0.861 to 0.989), and RLA measurements had the highest correlation with CT liver volume measurements (r = 0.94) of all radiographic measurements. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that RLA measurement in small-breed dogs with or without liver disease was useful and accurate for estimation of liver size, compared with CT measurement, and might be particularly useful for monitoring of changes in liver size.

Nematode eggs in liver tissues of two wild rats were recorded atthe Regional Veterinary Laboratory, Kota Bharu from 2014 to 2015. A total of 15 (2014) and 48 (2015) wild rats were examined by the laboratory for routine screening of zoonotic pathogens such as Leptospira sp. and others. On histological examination of the haematoxylin and eosin (H&E) stained liver tissues, masses of parasitic nematode eggs were observed. The shell of the eggsis striated with shallow polar prominences at either end. Numerous mini-pores can be seen on the outer shell as well. The eggswere identified as Capillaria hepatica (C. hepatica) nematode eggs, which causes hepatic capillariasis in rodents and numerous other mammal species, including humans. The wild rats were alsoshown to harbour Salmonella enteritidis from the intestine, E. coli from the lung and liver but none had leptospirosis by PCR. The purpose of this report is to highlight a common nematode of wildrats that is Capillaria hepatica infection in wild rats in Kelantan diagnosed by the Kota Bharu Regional Laboratory, in orderto create the awareness on concurrent parasitic infections which may cause reduced immunity thereby creating higher risk for other zoonotic pathogens such as leptospirosis.

Objective-To determine total glutathione (GSH) and glutathione disulfide (GSSG) concentrations in liver tissues from dogs and cats with spontaneous liver disease. Sample Population-Liver biopsy specimens from 63 dogs and 20 cats with liver disease and 12 healthy dogs and 15 healthy cats. Procedure-GSH was measured by use of an enzymatic method; GSSG was measured after 2-vinylpyridine extraction of reduced GSH. Concentrations were expressed by use of wet liver weight and concentration of tissue protein and DNA. Results-Disorders included necroinflammatory liver diseases (24 dogs, 10 cats), extrahepatic bile duct obstruction (8 dogs, 3 cats), vacuolar hepatopathy (16 dogs), hepatic lipidosis (4 cats), portosystemic vascular anomalies (15 dogs), and hepatic lymphosarcoma (3 cats). Significantly higher liver GSH and protein concentrations and a lower tissue DNA concentration and ratio of reduced GSH-to-GSSG were found in healthy cats, compared with healthy dogs. Of 63 dogs and 20 cats with liver disease, 22 and 14 had low liver concentrations of GSH (µmol) per gram of tissue; 10 and 10 had low liver concentrations of GSH (nmol) per milligram of tissue protein; and 26 and 18 had low liver concentrations of GSH (nmol) per microgram of tissue DNA, respectively. Low liver tissue concentrations of GSH were found in cats with necroinflammatory liver disease and hepatic lipidosis. Low liver concentrations of GSH per microgram of tissue DNA were found in dogs with necroinflammatory liver disease and cats with necroinflammatory liver disease, extrahepatic bile duct occlusion, and hepatic lipidosis. Conclusions and Clinical Relevance-Low GSH values are common in necroinflammatory liver disorders, extrahepatic bile duct occlusion, and feline hepatic lipidosis. Cats may have higher risk than dogs for low liver GSH concentrations.

Microcystin and related toxic peptides produced by cyanobacteria (blue-green algae) are potent and selective inhibitors of protein phosphatases 1 and 2A. We adapted existing enzymatic techniques to analyze the liver of rainbow trout after oral administration of hepatotoxic cyanobacteria. Liver tissue was removed 3 and 12 hours after treatment, and phosphatase activity was determined in liver extracts, using a specific phosphoprotein substrate. In all samples from fish exposed to toxic cyanobacteria, phosphatase activity was suppressed, whereas the control enzyme, lactate dehydrogenase, present in the same liver extract, was not affected by cyanobacteria. Thus, experimental poisoning by hepatotoxic cyanobacteria resulted in an abnormally low ratio of phosphatase to lactate dehydrogenase activity in the liver extracts. These results indicate that specific inhibition of phosphatases 1 and 2A may provide a useful diagnostic tool to determine the early effects of cyanobacteria toxic peptides directly in liver samples from poisoned animals. Although this test was developed with rainbow trout, it should be possible to extend the analysis of liver phosphatase activity to other species, including sheep and cattle, which are frequently affected by hepatotoxic cyanobacteria.

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 finding 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.

To differentiate the origin of high total lactate dehydrogenase (LD) activity in canine sera, a spectrophotometric method based on the preferential inhibition of cardiac LD isoenzymes by pyruvate was performed. Comparison with the electrophoretic separation of LD isoenzyme activities and determination of the hydroxybutyrate dehydrogenase-to-LD ratio indicated that the method proposed gave a better discrimination between cardiac and hepatic LD activities than did the other tests.

OBJECTIVE To evaluate stiffness of the liver parenchyma in healthy adult cats by means of point shear wave elastography (PSWE). ANIMALS 18 client-owned adult (1- to 6-year-old) healthy cats. PROCEDURES Echogenicity and echotexture of the liver parenchyma were assessed by means of conventional B-mode ultrasonography. The shear wave velocity (Vs) of the right and left portions of the liver were measured by means of PSWE. RESULTS B-mode ultrasonography revealed no abnormalities in echotexture or echogenicity of the liver parenchyma in any cat. Mean (95% CI) Vs in the liver parenchyma was 1.46 m/s (1.36 to 1.55 m/s) for the right portion, 1.36 m/s (1.26 to 1.47 m/s) for the left portion, and 1.43 m/s (1.35 to 1.51 m/s) overall. The difference in mean Vs between the 2 portions of the liver was significant. No significant correlation was found between Vs and body weight or between Vs and the depth at which this variable was measured. CONCLUSIONS AND CLINICAL RELEVANCE Quantitative PSWE of the liver was feasible in healthy adult cats. The obtained values for Vs may be useful for interpretation of and comparison with values measured in cats with liver disease. Additional research is needed to explore the potential usefulness of PSWE for diagnostic purposes.