Pharmacokinetic variables of skeletal muscle creatine kinase (CK) activity after IV administration of a muscle extract; CK bioavailability after IM administration of the muscle extract; and effect of IM administration of saline solution, to appreciate the possible release of CK consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on plasma CK activity (ANOVA, P > 0.05) in any of the cows. After IV administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of CK were 0.027 +/- 0.007 L/kg, 520 +/- 109 minutes, and 6.43 +/- 2.29 ml/kg/h, respectively. After IM administration (150 U/kg), mean bioavailability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 97 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours. Amplitudes were 6.31 +/- 4.45 and 6.57 +/- 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of CK liberated from control muscle was 0.69 +/- 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 +/- 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after IM administration of a test article: Qmuscle, test article (g/kg) = 4.41 X 10(-6) AUC (U/h/L), with AUC being the CK plasma activity area under the curve.

The cause of species difference in the susceptibility of erythrocytes to L-sorbose, and the difference in the hemolytic effect of sorbose on high potassium-containing (HK) and low potassium-containing (LK) canine erythrocytes were examined. L-sorbose was phosphorylated in canine erythrocytes, but not in human erythrocytes. Furthermore, sorbose-1-phosphate, a metabolite of L-sorbose, strongly inhibited the hexokinase of LK canine erythrocytes, but not that of HK canine erythrocytes. These results strongly indicated that inhibition of hexokinase by sorbose-1-phosphate in LK erythrocytes induced severe glycolytic limitation in these cells, resulting in hemolysis, and that HK erythrocytes are resistant to sorbose-induced hemolysis because these cells have a high hexokinase activity.

Cerebrospinal fluid and serum were obtained from 17 adult, healthy llamas (9 males, 1 castrated male, and 7 females). Osmolality; activities of lactate dehydrogenase and creatine kinase; and concentrations of glucose, sodium, chloride, potassium, total protein, and albumin were determined in serum and CSF. Total and differential cell counts were determined in CSF, and electrophoresis of CSF proteins was performed. Total nucleated cell count was low, 0 to 3/microliter, which is lower than that reported for other domestic species and is similar to values in healthy people. Differential leukocyte percentages were disparate depending on the degree of blood contamination. Blood contamination influenced the percentage of neutrophils and eosinophils in CSF. Samples with few erythrocytes had differential leukocyte distribution similar to that of other species: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Older llamas had a few eosinophils in the CSF. Total protein, albumin, and gamma-globulin concentrations in llamas were similar to values in cattle and were higher than values in most domestic species. Glucose concentration in CSF was approximately 40% of the value in serum (nonruminant animals and people typically have CSF glucose concentration that is approximately 60 to 80% of the serum glucose concentration). Sodium and Cl concentrations in CSF were higher than those in serum, whereas K concentration was lower in CSF, compared with serum. Activities of creatine kinase and lactate dehydrogenase in CSF were markedly lower than those in serum, and the ranges of values in this group of healthy llamas were narrow.

A former secondary lead smelter was in operation in Granite City, Ill, until the early 1980s. As a result, the surrounding area is heavily contaminated with lead. Soil concentrations as high as 5,000 ppm have been measured in prior studies. Because of growing concerns about health defects associated with low levels of lead exposure in human beings, a major study has been conducted on people living in the area. The study reported here was a corollary to the human exposure study. Lead concentration was determined in 84 dogs and 26 cats in the town and ranged between < 5 and 28 microgram/dl. None of the dogs had clinical signs of lead poisoning. The CBC and serum biochemical values did not indicate many significant differences between dogs with a high (larger than or equal to 10 microgram/dl) or low blood lead concentration (BLC). Hemoglobin concentrations were lower, and WBC counts were higher in dogs and cats with higher BLC, but they were still within reference ranges. Free erythrocyte protoporphyrin concentration was determined. Normal values appeared to be similar for dogs and cats. Only animals with BLC larger than or equal to 20 microgram/dl were found to have somewhat increased concentration of free erythrocyte protoporphyrin. Delta-aminolevulinic acid dehydratase activity was measured and found to be negatively correlated with BLC. The relation was strong, even at low BLC (5 to 10 microgram/dl) in both species. Age or sex difference was not observed. Therefore, biological changes associated with low BLC were limited to BLC in the 10- to 30-microgram/dl range.

To assess right colic artery blood flow and relevance of xanthine dehydrogenase/xanthine oxidase after experimentally induced strangulation obstruction and reperfusion of the colon, 5 ponies were subjected to 2.5 hours of complete ischemia of the left dorsal and ventral colons, allowed to recover from surgery, and monitored during a 48-hour reperfusion period. Five ponies were subjected to sham surgery and served as controls. All ponies had a Doppler ultrasound blood flow monitor implanted on the right colic artery near the pelvic flexure 10 to 14 days prior to the ischemic period. Colic artery blood flow was monitored prior to, during, and for 4 hours after surgery. Blood samples from the right colic artery and vein distal to the obstruction site were collected during surgery (prior to ischemia, after 1 and 2 hours of ischemia, and after 10 and 60 minutes of reperfusion) for determination of arterial and venous blood gas tensions and electrolytes. Prior to surgery, blood selenium and plasma vitamin E (alpha-tocopherol) concentrations and blood glutathione peroxidase (GPX) activity were determined to assess the status of endogenous antioxidants. Combined xanthine dehydrogenase (XDH) plus xanthine oxidase (XO) activity, and XO activity alone (nanomoles per minute per gram of tissue) were determined, using a dual-spectrophotometric technique. Xanthine dehydrogenase and oxidase activities were determined prior to ischemia, after 1 and 2 hours of ischemia, and at 1 and 48 hours after reperfusion. Median blood flow in the experimental and control groups (156 ml/min and 110 ml/min, respectively) was not statistically different before surgery, and was significantly (P < 0.02) lower in the experimental (4 ml/min) vs the control group (72.5 ml/min) during the ischemic period. Experimental ponies had significantly (P < 0.03) lower right colic artery blood flow during the 4 hours immediately after recovery from anesthesia. Significant difference was not observed in right colonic venous bicarbonate concentration between groups at any time. Median right colonic venous P(CO2), pH, and standard base excess were different (P < 0.001) between groups during the ischemic period only. Median venous oxygen saturation and median venous P(O2) were significantly (P < 0.001) lower in the experimental ponies at the end of 2 hours of ischemia, but were significantly (P < 0.05) increased during the reperfusion phase. Median venous potassium concentration was significantly (P < 0.01) higher in experimental ponies during the ischemic and reperfusion phases. Vitamin E and GPX values were within normal limits for all ponies. Median selenium concentration was < 15 microgram/dl; however, there were no significant differences between control and experimental ponies. Only 3 of 10 ponies had measurable XHH/XO activity at the beginning of the experiment. Enzyme activity was detected in 1 additional pony during the ischemic period. However, in all 4 ponies in which XDH/XO activity was detected, enzyme activity was low (10 to 36 nmol/min/g). On the basis of macroscopic and histologic examination of the large colon, evidence of reperfusion injury was not found in 4 of the 5 experimental ponies. The only pony with gross evidence of reperfusion injury did not have detectable XO activity. Results of the study indicate that hypoperfusion of the colon during the postischemic period may be a factor in deterioration of the colon observed clinically in equids with surgical correction of large-colon volvulus. Additionally, if reperfusion injury develops in the large colon, it probably is not mediated through the xanthine oxidase enzyme system: the activity of this enzyme in the large colon, when present, is negligible.

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.

Diamine oxidase (DAO), an enzyme of small intestinal origin, is released from mucosal storage sites by IV administration of heparin, to yield the plasma postheparin DAO (PHD) curve. The PHD curve is diminished when mucosal surface area is lost, and baseline (without heparin) plasma DAO activity increases when mucosal storage sites are damaged. Plasma DAO activity was measured after 2 doses of heparin were administered Iv in healthy, conscious horses. In anesthetized horses, the PHD curve was studied: during sham small intestinal surgery, and during venous strangulation obstruction (VSO) of the distal 50% of the small intestine. In a third group of anesthetized horses, baseline plasma DAO activity (without heparin) was measured during vso of the distal 50% of the small intestine for 90 minutes, followed by reperfusion for 90 minutes. Postheparin plasma DAO curves in conscious horses were similar to those reported in other species Horses with VSO had a similar PHD curve as did sham-operated controls at all times, except at 15 minutes, when plasma DAO activity was significantly (P < 0.05) greater in the vso group. Horses with VSO and reperfusion had no change in baseline plasma DAO activity throughout the study. Peritoneal fluid DAO activity remained low throughout the study, but increased slightly in horses with VSO that received heparin, possibly because of DAO from extravasated blood in the peritoneal fluid. Results indicated that the plasma DAO response to IV administered heparin in horses is similar to that in other mammals, but, unlike other species, baseline and postheparin DAO activities did not change as expected after small intestinal vascular obstruction and mucosal injury. There may be additional sources of DAO in horses, the type of injury induced was not of sufficient magnitude to affect storage sites of DAO, or the circulatory changes induced by vso might have altered tissue delivery of heparin.

Drug-metabolizing enzyme activities were measured in livers from calves fed commercial milk replacer (nonfunctioning rumen [veal]), and those fed milk replacer supplemented with whole grain and hay from the first week of age (functioning rumen [ruminating calves]). After birth, cytochrome P450 and its NADPH-dependent reductase activities remained unchanged in veal calves; in ruminating calves they increased almost 50%. Cytochrome P450-mediated reactions, such as aniline hydroxylase activity, tripled in ruminating calves, but remained unchanged in veal calves. In both groups of calves, coumarin hydroxylase and 7-ethoxycoumarin 0-deethylase activities increased after birth, but maturation rates and activity values in ruminating calves were considerably greater than those of veal calves. The aminopyrine N-demethylase activity for veal calves was equal to that of calves with functioning rumen. Uridine diphosphoglucuronic acid glucuronyl transferase and glutathione-S-transferase activities also were higher in calves with functioning rumen than in veal calves. This increased activity in calves with functioning rumen probably represents a response to environmental exposure to xenobiotics. Compared with rumen-functional calves, bob veal (0 to 3 weeks old) and fancy veal (15 to 19 weeks old) calves fed commercial milk replacer have a significantly (P = 0.05) diminished capacity for metabolizing drugs and other xenobiotics. From a regulatory perspective, the variance in drug-metabolizing enzyme activities within these different market classes of calves suggests that specific studies designed to determine drug residue-depletion times in veal calves may be needed.