Serum interleukin-6 (IL-6) concentration was measured in 11 colostrum-fed (CF) and 8 colostrum. deprived (CD) 2- to 3-day-old foals after foals were infused with lipopolysaccharide LPS; Escherichia coli O55:B5 endotoxin, 0.5 micrograms/kg of body weight in sterile saline [0.9% NaCl] solution. Four CF and 2 CD foals were given saline solution alone. Serum IL-6 concentration was estimated by use of an in vitro proliferative bioassay, using the IL-6 dependent B.13.29 clone 9 cells. Interleukin-6 concentration increased in all LPS-infused foals, and geometric mean serum IL-6 concentration was significantly higher in CF than CD foals 30 and 90 minutes after infusion. Both LPS-infused. groups had multiple spikes of mean IL-6 concentration that peaked at 120 minutes in CF foals and 150 minutes in CD foals. Results indicated that IL-6 is produced in neonatal foals in response to LPS infusion. Furthermore, colostrum deprivation resulted in longer times to peak mean serum IL-6 concentration and tended to reduce serum IL-6 concentration in neonatal foals.

The effects of exogenous platelet-activating factor (PAF) were determined in anesthetized ponies. Administration of PAF induced a decrease in cardiac index that resulted in systemic hypotension. This was followed by tachycardia, hypertension, and a return of cardiac index to baseline. Pulmonary arterial pressure increased markedly because of pulmonary vasoconstriction. Exogenous PAF also caused leukopenia and thrombocytopenia. The specific PAF receptor antagonist (WEB 2086) blocked all PAF-induced changes. Flunixin meglumine, a cyclooxygenase inhibitor, abolished the pulmonary hypertension and tachycardia, and attenuated the systemic hypotension but did not change the PAF-induced peripheral cellular changes. The PAF antagonist also inhibited platelet aggregation induced by PAF in vitro. The PAF-induced changes are similar to those reported after endotoxin exposure in horses.

Semen from three stallions was used to evaluate the effectiveness of two antibiotics added to semen extender for samples stored at 20 degrees C or 5 degrees C for up to 48 hours. Each ejaculate was divided into six different treatments: semen+extender (SE); SE+gentamicin (100 micrograms/mL); SE+polymyxin B (1000 units/mL); and each of the above treatments inoculated with Pseudomonas aeruginosa ATCC 27853. Sampling of diluted semen for bacteriological analysis was performed after 2, 8, 24 and 48 hours of preservation at either temperatures. The presence of nonspecific bacteria was noted after two hours in all SE aliquots. The number of bacteria did not change in samples stored at 5 degrees C, while in samples preserved at 20 degrees C, it increased by three to four times after 48 hours. In semen aliquots treated with either of the antibiotics, the number of nonspecific bacteria was very low after two and eight hours at both temperatures. This number remained stable up to 48 hours at 5 degrees C, while an increase was noted at 24 and 48 hours at 20 degrees C. At 5 degrees C, the number of P. aeruginosa cells tended to decrease between 24 and 48 hours in SE aliquots. The presence of gentamicin or polymyxin B appeared to rapidly inhibit growth of P. aeruginosa. At 20 degrees C, growth of P. aeruginosa increased between 8 and 24 hours in SE, while the presence of antibiotics almost completely inhibited the growth of the bacterium. In conclusion, gentamicin and polymyxin B appeared effective for the control of P. aeruginosa at either temperature, but nonspecific bacteria increased after 24 and 48 hours at 20°C.

After IV administration of 0.5 mg of glucagon/cat, glucose tolerance and insulin secretory response were evaluated in 10 lean cats, 10 obese cats, and 30 cats with diabetes mellitus. Blood samples for glucose and insulin determinations were collected immediately before and at 5, 10, 15, 30, 45, and 60 minutes after IV administration of glucagon. Baseline serum insulin concentration and insulin secretory response were used to classify diabetes mellitus in the 30 cats as type I or type II. Mean (+/- SEM) baseline and 30-minute serum glucose concentrations in obese cats were significantly (P < 0.05) decreased, compared with values in lean cats, but were similar at all other blood sample collection times. Serum glucose concentration in diabetic cats was significantly (P < 0.05) greater than values in obese and lean cats at all blood sample collection times. Two statistically different insulin responses to IV administration of glucagon were seen in diabetic cats. Of the 30 diabetic cats, 23 had minimal insulin secretory response after glucagon administration (ie, serum insulin concentration was at or below sensitivity of the insulin assay). Seven diabetic cats had baseline serum insulin concentration similar to that of obese cats and significantly (P < 0.05) greater than that of lean cats and of the other 23 diabetic cats. In these 7 diabetic cats, serum insulin concentration increased after glucagon administration. Total insulin secretion was not significantly different between these 7 diabetic cats and the lean and obese cats, and was significantly (P < 0.05) greater than total insulin secretion in the other 23 diabetic cats. Results support existence of type-I and type-II diabetes mellitus in cats.

Pharmacokinetic variables of ibuprofen were studied in 6 adult lactating dairy goats after single administration of the drug (14 and 25 mg/kg of body weight, IV, and 50 and 100 mg/kg, PO). Each of the goats was given all doses, with a minimum of 1 week between doses. Ibuprofen concentration in serum was analyzed by use of high-performance liquid chromatography. The lower limit of detection for the ibuprofen assay was 50 ng/ml. Ibuprofen pharmacokinetic variables after IV administration best fit an open two-compartment model. Geometric mean (range) volume of distribution at steady state was 0.16 (0.11 to 0.19) and 0.17 (0.15 to 0.19) lag, and terminal half-life was 1.08 (0.79 to 1.70) and 1.27 (1.03 to 1.88) hours, for ibuprofen dosages of 14 and 25 mg/kg, respectively. After 50 and 100 mg/kg administered orally, bioavailability was 90.8 and 106%, respectively. Area under the curve increased linearly with dose administered. Adverse effects were not observed in goats given ibuprofen.

The pattern of vertical ground reaction force redistribution among limbs during episodes of acute synovitis of the stifle in 12 mixed-breed dogs was investigated as an adjunct to a blinded nonsteroidal anti-inflammatory drug efficacy study. Without regard to drug efficacy groupings, the redistribution of vertical forces before and during the acute synovitis episode was evaluated by analysis of gait, using a force platform. Acute synovitis was induced by intrasynovial injection of sodium urate crystals. Simultaneously, each dog was given 1 of 4 treatment regimens, including IV injection of sterile saline solution (as a negative control), phenylbutazone (as a positive control), or 1 of 2 proprietary nonsteroidal anti-inflammatory drugs. Postinjection analyses took place at 2, 4, 8, 12, 24, and 36 hours. The peak vertical force redistribution in the 3 untreated limbs of the dogs was described. The greatest redistribution sm observed 4 hours after substance injection when the synovitis was clinically at maximum. Thereafter, there was steady improvement and the dogs had a clinically normal gait 24 hours after substance injection. During synovitis, peak vertical force increased in the contralateral hind limb. During the more severe synovitis episodes, force was decreased in both forelimbs. There was good correlation between severity of lameness and peak vertical force response in the contralateral hind limb. Results of the study indicate that the untreated limbs of the same animal should not be used as a control during acute lameness studies.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs commonly used for the management of colic, endotoxemia, and musculoskeletal disorders in equids. Although it is not usually recommended, there appears to be an increasing trend to use nonsteroidal anti-inflammatory drugs in combination to enhance or prolong their effects. Therefore, we studied the effect of concurrent administration of flunixin (1.1 mg/kg of body weight, IV) as flunixin meglumine and phenylbutazone (2.2 mg/kg, IV) on the pharmacokinetics of each drug and on in vitro thromboxane B2 production. Pharmacokinetic variables calculated for each drug when given alone and in combination were similar to those reported. Serum thromboxane B2 production was significantly (P = 0.05) suppressed for 12, 8, and 24 hours after administration of flunixin, phenylbutazone, and the drugs in combination, respectively. These results indicate that although concurrent administration of these drugs at the aforementioned dosages does not alter either drug disposition or clearance, it prolongs their pharmacologic effect.

Desoxycorticosterone pivalate was administered IM to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and BUN concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.

Ouabain, a cardiac glycoside, binds to the Na+-K+i-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP were compared with age-matched clinically normal horses. The number of [3H]ouabain-binding sites in adult gluteal muscle was not different between the 2 types of horses (85.7 +/- 8.9 pmol of [3H]ouabain-binding sites/g [wet muscle weight] in horses with HYPP vs 100.2 +/- 8.8 pmol/g in clinically normal adult horses). Gluteal muscles in HYPP-affected and clinically normal foals also contained a similar number of [3H]ouabain-binding sites (222.3 +/- 21.0 pmol/g vs 225.3 +/- 24.2 pmol/g, respectively). The affinity of these binding sites for ouabain was not different, between adults or foals, in clinically normal or affected horses. Our results indicate that membrane events underlying the periodic episodes of paralysis in horses with HYPP are not attributable to quantitative changes in Na+ pump number or affinity. Our data cannot exclude the possibility that the specific activity of the Na+ pump is altered in muscle from HYPP-affected horses.