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.

Influence of age, breed, and stage of pregnancy on hepatic ultrasonographic findings of cows was determined. In addition, the relation between body weight, height at the withers, milk production, and the measurements determined via ultrasonography was investigated. The liver of 186 cows was examined ultrasonographically. The cows comprised Swiss Braunvieh, Simmental, and Holstein breeds, and age ranged from 2.5 to 11.5 years. The ultrasonographic findings of the liver, gallbladder, caudal vena cava, and portal vein were described, and the position, size, thickness, and distal angle of the liver were determined. In addition, the position and diameter of the caudal vena cava and portal vein were determined. There was no significant difference between any of the variables determined and breed or age. Therefore, measurements for the 3 breeds and for the various ages were summarized into 1 group. There were significant correlations between body weight, milk production, and size and thickness of the liver. In 3 pregnant cows, the liver was examined ultrasonographically 8 times during the course of pregnancy. Positive correlation was detected between stage of pregnancy and diameter of the caudal vena cava. There was a negative correlation between stage of pregnancy and diameter of the portal vein. In 23 cows, the ultrasonographically determined measurements of the liver were compared with those determined at slaughter. Weight of the liver correlated well to thickness of the liver determined via ultrasonography.

Sheep given powdered Ferula communis variety brevifolia at dosage of 2.5 g/kg of body weight/d for 15 days developed classical clinical signs of intoxication: anorexia, somnolence, apparent weakness, and hemorrhage. Marked reduction of vitamin K-dependent coagulation factors and prolongation of prothrombin time and activated partial thromboplastin time were consistent with presence of ferulenol, a toxic coumarinic factor in the plant. Changes induced in the coagulation system developed by the second day of plant administration and were normal within 4 days after dosing was stopped. There was no evidence of primary liver damage or platelet malfunction. Of 6 intoxicated sheep, 2 died with only minimal evidence of hemorrhage.

Intrareticularly placed sustained-release selenium boluses were administered to 1 group of selenium-deficient heifer calves (n = 16), and a second group (n = 16) was left as nontreated controls. Age range for all calves was 83 to 156 days. These boluses release 3 mg of selenium each day, as sodium selenite. Measurements of blood selenium concentration, plasma copper concentration, hepatic copper concentration, and body weight were made over a 188-day day study. The treated group of calves had significantly higher mean blood selenium concentration at posttreatment days 68 (P < .0001), 112 (P < 0.0001), and 188 (P < 0.005) than did the control group. Mean blood selenium concentration in the treated calves was > 0.10 micrograms/ml for 188 days. These boluses were observed to be clinically safe; signs of selenium toxicosis were not detected and untoward effects were not seen in the selenium-treated calves. There were no differences between control and treatment groups with respect to mean hepatic copper concentration or mean plasma copper concentration. There were no observed differences between the control and treatment groups with respect to weight gain during the study.

The reticulum and adjacent organs were mined ultrasonographically in 51 cows by use of a 3.5-Mhz linear transducer applied to the ventral aspect of the thorax over the sixth and seventh intercostal spaces. Examination included assessment of the contour of the reticulum, of reticular contractions, and of the organs adjacent to the reticulum. The normal reticulum appeared as a half-moonshaped structure with a smooth contour; it contracted at regular intervals and was situated immediately adjacent to the diaphragm and ventral portion of the abdominal wall when relaxed. Contents of the reticulum could not normally be imaged because of its partly gaseous composition. The ruminoreticular groove, craniodorsal blind sac of the rumen, and the ventral sac of the rumen were observed caudally. The distal aspect of the spleen and parts of the omasum, abomasum, and liver could be imaged. Reticular motility was characterized by a biphasic contraction pattern. Four biphasic reticular contractions usually were observed during a 4-minute period. During the first (incomplete) contraction, the reticulum contracted by a mean of 7.2 +/- 2.30 cm. There was then low-grade, incomplete relaxation of the reticulum, followed immediately by the second reticular contraction, during which the reticulum usually disappeared from the 17.5-cm-deep screen. The reticulum then reappeared in its normal position. The first reticular contraction lasted a mean of 2.6 +/- 0.33 seconds and the second contraction lasted 3.9 +/- 0.55 seconds. The mean interval between 2 biphasic contractions was 44.9 +/- 10.53 seconds. The speed of the first reticular contraction was 5.4 +/- 1.32 cm/s. Ultrasonography was useful for assessing the contour and motility of the reticulum.

Hepatobiliary scintigraphy provides a noninvasive assessment of hepatobiliary structure and function, and has been used extensively in people. Hepatocellular measurements determined in the cats of this study include cardiac washout (less than or equal to 2 minutes) and time of maximal hepatic activity (less than or equal to 5 minutes) and hepatic washout (less than or equal to 30 minutes). The gallbladder response to synthetic cholecystokinin was determined to be less than or equal to 3 minutes. Additional measurements also were identified. Potential use of hepatobiliary scintigraphy in feline medicine is discussed.

High serum alkaline phosphatase (ALP) activity is considered a sensitive marker of cholestasis in most mammalian species, including dogs. Induction of high serum ALP activity in association with cholestasis is dependent on high hepatic bile acids concentrations. Treatment of dogs with glucocorticoids also results in high serum ALP activity. The possible causal relation between serum ALP activity and bile acids concentration was investigated in dogs treated with glucocorticoids. The relation of glucocorticoid treatment to changes in the activity of individual ALP isoenzymes, alanine transaminase (ALT) and gamma-glutamyltransferase (GGT) also was investigated. Eight conditioned dogs were given 4 mg of prednisone/kg of body weight, IM, daily for 10 days. Blood samples were taken prior to treatment and on treatment days 3, 5, 7, and 10. Liver tissue was then taken from each dog. Serum total ALP activity was significantly (P < 0.05) high at day 3 in prednisone-treated dogs. Isoenzyme analysis indicated that this increase was attributable to an increase in the liver ALP isoenzyme (LALP). Significant increases in serum corticosteroid-induced ALP (CALP) and bone ALP were first observed on days 7 and 10, respectively. Serum ALT and GGT activities were significantly increased by day 5. Increased serum or hepatic tissue bile acids concentrations were not observed in prednisone-treated dogs, compared with values in 8 clinically normal (control) dogs, but were high in 3 dogs with complete bile duct ligation. Hepatic activities of LALP, CALP, and GGT were higher in prednisone-treated dogs than values in controls, indicating probable increased hepatic synthesis of these enzymes. Hepatic ALT activity was not increased. The ratio of serum to tissue LALP activity was increased in prednisone-treated dogs, compared with values in controls, indicating that LALP may have been preferentially released into serum. There was no difference in the ratio of serum to liver GGT activity between prednisone-treated dogs and controls. The LALP and GGT ratios were increased in bile duct-obstruction dogs. It was concluded that, although LALP is the principal ALP isoenzyme in serum during the first 10 days of prednisone treatment, hepatic bile acid concentrations are not increased and, therefore, are not likely to be responsible for induction and release of ALP into serum. Prednisone may, therefore, be directly responsible for induction of ALP activity in dogs treated thusly.

Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4)M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6)M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8)M dexamethasone. Dexamethazone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

In rats infected with the cestode Taenia taeniaeformis, hepatomegaly results from development of parasitic cysts in the liver. Diffuse nodular mucosal hyperplasia in the glandular region (corpus and antrum) of the stomach, and gross thickening of the intestinal mucosa also result. Between postinfection days (PID) 21 and 84, radiologic observations were made after oral administration of a barium sulfate suspension in T taeniaeformis-infected rats and in age/sex-matched controls. There was radiographic evidence of hepatic enlargement at PID 21. Enlargement of the gastric folds was first observed along the greater curvature of the stomach at PID 35. Fimbriation of small intestinal mucosal surfaces resulted from thickening of the intestinal villi and was observed in the duodenum at PID 21. Intestinal motility was assessed, and contractions were counted, using image intensification fluoroscopy, then were recorded on videotape. There were no significant differences between control and infected rats for gastric emptying time, intestinal transit time, and number of intestinal contractions per minute. Barium contrast radiography clearly indicated large gastric folds, thickening of the small intestinal villi, and hepatic enlargement, and was useful for assessing gastrointestinal motility.