On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the hoof twitch (eg, digital extensor) occurred with simultaneous quantification of blood values of metocurine. Pharmacokinetic and pharmacodynamic analyses of the data were done by a nonlinear regression program, using the Hill equation. There were no differences in findings between exercised and nonexercised horses. The mean blood concentration for the 50% paralyzing dose of metocurine was 0.44 +/- 0.11 (SD) micrograms/ml in exercised horses, and 0.58 +/- 0.22 micrograms/ml in nonexercised horses. Despite evidence for a response to conditioning, a significant change in the sensitivity of the neuromuscular junction to metocurine was not found.

Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only PAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.

The effect of metoclopramide (MC), a dopamine antagonist on luteinizing hormone (LH), was examined in anestrous primaparous cows. Metoclopramide has been found to be beneficial in overcoming fescue toxicosis; increasing LH secretion stimulates return to ovulatory function after parturition. Consequently, if MC had negative effect on LH secretion, it would indicate that administration of MC to reproducing animals might be limited. Of 14 postpartum (47 to 66 days) cows, 7 were given MC (4 mg/kg of body weight, IV), and 7 served as controls. Blood was obtained via jugular cannulas at 15-minute intervals for 8 hours; MC was given at the end of the first hour, and gonadotropin-releasing hormone (GnRH, 7 mg/kg), was given IV at the end of hour 7 as a challenge stimulus for LH secretion. Prior to GnRH administration, MC did not have significant effect on LH secretion, as judged by mean serum LH concentration, LH pulse frequency, and LH pulse amplitude. Administration of MC resulted in greater (P < 0.05) LH response to GnRH, indicating enhanced secretory ability when the pituitary gland was challenged. Serum prolactin concentration was increased (P < 0.01) by MC administration. Therefore, MC did not have adverse effect on LH secretion in postpartum cows.

In 2 trials, the efficacy of an in-feed preparation of ivermectin was evaluated in 40 pigs naturally infected with endoparasites and Sarcoptes scabiei var suis. Treated pigs (n = 10 in each trial) were fed a ration containing 2 ppm ivermectin for 7 days, followed by consumption of a nonmedicated ration for the remainder of the trial. Control pigs (n = 10 in each trial) were fed a complete, nonmedicated ration for the duration of the trial. Pigs in trial A were monitored for 14 days after treatment; those in trial B were monitored for 35 days after treatment. In trial A, treatment efficacy of ivermectin was 100% against Ascaris suum, Physocephalus sexalatus, Oesophagostomum dentatum, O brevicaudum, Metastrongylus spp; 99.8% against Ascarops strongylina; 90.9% against Trichuris suis; and 13.1% against Macracanthorhynchus hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were observed between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Oesophagostomum spp. On posttreatment day 14, S scabiei were not found in any scrapings taken from treated pigs, but were found in scrapings from 3 of 10 control pigs. The number of infested pigs in the treatment group was not statistically different from the number of infested pigs in the control group. In trial B, treatment efficacy was 100% for A suum and Metastrongylus spp; 96.9% for Ascarops strongylina; and 76.9% for M hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were evident between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Metastrongylus spp. On posttreatment days 7, 2 1, and 35, S scabiei were not found in scrapings taken from treated pigs. On posttreatment days 7, 2 1, and 35, S scabiei were found in scrapings from 8, 6, and 1 pig, respectively, whereas live mites were not found on scrapings taken from treated pigs on these days. Statistically significant (P < 0.05) differences were evident between the numbers of infested pigs in the treated and control groups on days 7 and 21. Ivermectin fed to swine ad libitum in a complete ration at 2 ppm was shown to be highly effective as an anthelmintic and acaricide.

Acyloxyacyl hydrolase (AOAH) is a lysosomal enzyme found in neutrophils and macrophages that acts to partially deacylate the lipid-A component of the endotoxin of gram-negative bacteria rendering it less toxic, yet maintaining much of its immunostimulatory potential. We have found that the activity of neutrophil AOAH per cell increased during localized inflammation. The purpose of this study was to determine the mechanism(s) responsible for these increases in neutrophil AOAH activity. Because changes in neutrophil maturity commonly are associated with inflammation, intravascular infusion of purified gram-negative bacterial lipopolysaccharide and SC injection of bovine recombinant granulocyte colony-stimulating factor was used to induce large numbers of circulating immature neutrophils. Immature neutrophils were found to have AOAH activity equal to that of mature cells; however, when neutrophils were stimulated in vitro with known activators, AOAH activity of activated cells was more than that of unstimulated cells. The increase in AOAH activity was inversely related to prestimulation activity. Increases in AOAH activity after neutrophil activation were not a result of de novo synthesis of the enzyme, because cycloheximide did not prevent activation-induced increases in activity.

Because articular chondrocytes are a target for drugs that can influence the integrity of cartilage, we investigated the effects of 3 antiarthritic drugs, glycosaminoglycan polysulfate, diclofenac-Na, and S-adenosylmethionine sulfate p-toluenesulfonate on total protein, fibronectin, and DNA synthesis, as well as on extradomain-A fibronectin and keratan sulfate content. Glycosaminoglycan polysulfate stimulated dose-dependent incorporation of [35S]methionine into protein and fibronectin, whereas incorporation of [3H]thymidine into DNA was unaffected. Total fibronectin, extradomain-A fibronectin, and keratan sulfate content were high in chondrocyte cultures treated with glycosaminoglycan polysulfate. In contrast, fibronectin and DNA synthesis, as well as extradomain-A fibronectin and keratan sulfate content were unaffected by diclofenac-Na. S-adenosylmethionine decreased dose-dependently the synthesis of fibronectin, as well as the content of fibronectin and keratan sulfate. At the highest concentration of S-adenosylmethionine tested, findings suggest that cell viability was impaired as assessed by the release of lactate dehydrogenase into the media.

Contact wide-field specular microscopy was performed on eyes of 16 healthy dogs after tissue plasminogen activator at a concentration of 25 microgram/100 (group 1, n = 8) or 50 microgram/100 microliter (group 2, n = 8) was injected into 1 anterior chamber of each dog. The contralateral eye served as a nontreated control. Applanation tonometry was used to measure intraocular pressure in both eyes for up to 168 hours. By use of computerized morphometric analysis and pachymetry, changes from baseline values in endothelial cell density, cell morphologic features, and corneal thickness were evaluated at postinjection, hours 24, 48, and 168. Significant mean differences in intraocular pressure were not detected between treated eyes of group-1 dogs and those in group 2 at designated times, or between treated and nontreated eyes of dogs in either group. Mean corneal thickness of treated and nontreated eyes was similar in both groups through postinjection hour 168. Changes in mean percentage of endothelial cell sides were observed only in treated eyes of group-2 dogs, with the mean percentage of hexagons at postinjection hour 168 decreasing by 18%, a decrease that was significantly (P < 0.05) greater than the decrease in nontreated eyes. The mean percentage of 6-sided cells in treated eyes of group-2 dogs was significantly (P < 0.05) less than that in treated eyes of group-1 dogs at postinjection hour 168.

Porcine blood mononuclear cells (BMC) were exposed to prepartum concentration of estrogen in gilts before acquisition (in vivo), and their subsequent reactivity (in vitro) was explored. In a cross-over experimental designed study, 6 ovariectomized gilts were injected once with 3.75 mg of estradiol-17beta benzoate in arachidic oil or with arachidic oil only during 2 experiments. The ability of their BMC to proliferate in response to stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen was assayed in cultures of blood and in cultures of purified BMC. After 2 days of mitogen stimulation, activity of accessible interleukin 2 was quantified in supernatants obtained from cultures of purified BMC and supernatants of blood cultures stimulated with pokeweed mitogen. Also, production of immunoglobulins by purified BMC in response to polyclonal stimuli was measured. Three days after treatment with estradiol, the proliferative response was suppressed in blood cultures stimulated with concanavalin A (P < 0.05) and phytohemagglutinin (P < 0.07). Effects of estradiol treatment were not found in any of the assays performed with purified BMC. We, therefore, assumed that in vivo exposure to estradiol can affect the function of porcine BMC; however, this was only evident when the in vitro assays were performed on blood cultures.

Addition of alanine and taurine blocked killing of lymphocytes caused by culture at 45 C. The optimal concentration for thermoprotection was achieved at 12.5 mM for L-alanine and 5 mM for taurine. Both D and L forms of alanine provided thermoprotection. The effect of these agents was not simply to increase osmolarity of the culture medium, because NaCl did not provide thermoprotection at comparable concentrations. Alanine and taurine were each tested at concentration of 50 mM for ability to block heat shock-induced killing and developmental retardation of 8- to 16-cell mouse embryos. Both agents enhanced embryo development after exposure to high temperature, though development remained less than that for embryos not exposed to high temperature. In one experiment, for example, 81% of embryos cultured at 38 C advanced in development during culture vs 0% at 42 C, 15% at 42 C with alanine, and 32% at 42 C with taurine. The beneficial effect of alanine at high temperature may have been partly attributable to effects independent of thermoprotection, because development of embryos cultured at 38 C was also improved by alanine.

We evaluated the effect of anticoagulant (lithium heparin, sodium heparin, or none) and type of autoanalyzer on selected blood biochemical values of the loggerhead sea turtle (Caretta caretta). More differences were observed between the analytes in serum and those in the 2 types of plasma than were observed between the 2 types of plasma. Differences in electrolyte concentrations were not significant when plasma from sodium-heparinized blood was compared with plasma from lithium-heparinized blood. Serum is not recommended for reptilian studies because clot formation is unpredictable and because the time required for clotting may allow substantial changes in the chemical composition of the sample. For most determinants, values varied more between the 2 types of autoanalyzers than among the 3 anticoagulant treatments. These sources of variation must be considered when performing comparative studies.