Articular cartilage explants from 3 horses were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan on proteoglycan biosynthesis. Cultures were exposed to concentrations of 0, 50, or 200 microgram of the drug/ml for either 2 days or 6 days, and labeled with 35S, before measuring the content of sulfated proteoglycan in the culture media and in extracts of cartilage. In a second experiment, the explants were incubated with the isotope and subsequently exposed to the same concentrations of the polysulfated glycosaminoglycan for 4 days. Subsequently, the amount of remaining labeled proteoglycan was determined. Gel filtration chromatography was used to compare the hydrodynamic size of proteoglycans from the cartilage explants in each experiment. Polysulfated glycosaminoglycan caused a dose-dependent depression of sulfated proteoglycan synthesis, which was statistically significant after 6 days of exposure. Radioactive proteoglycan content in explants was similar in the experiment involving isotopic labeling prior to exposure to the drug. Proteoglycan monomer size was similar in all treatment groups. It was concluded that polysulfated glycosaminoglycan caused a modest depression in proteoglycan synthesis, had little effect on endogenous proteoglycan degradation, and did not influence the size of sulfated proteoglycans synthesized by normal equine chondrocytes in explant culture.

The thiamylal sparing effect of midazolam was studied in 30 healthy Beagle and mixed-breed dogs. Using a replicated Latin square design, all dogs were given placebo (saline solution) and 0.025, 0.05, 0.1, and 0.2 mg of midazolam/kg of body weight prior to IV administration of thiamylal sodium. The 0.1 and 0.2 mg/kg dosages significantly decreased the amount of thiamylal required to obtund swallowing reflex and easily achieve endotracheal intubation. Midazolam at 0.1 and 0.2 mg/kg reduced thiamylal requirement by 16.4% and 18.9%, respectively, whereas the 0.05 mg/kg dosage decreased thiamylal requirement by only 6.8%. The 0.2 mg/kg dosage did not further decrease thiamylal requirement beyond that achieved with the 0.1 mg/kg dosage of midazolam. This study demonstrates that the preanesthetic IV administration of midazolam reduces the thiamylal dose necessary to accomplish intubation. The optimal preanesthetic dosage (lowest dosage with significant effect) was 0.1 mg/kg.

Eight ponies were allotted to 2 groups of 4. Group-1 ponies (1-4) were given 0.2 g of indole/kg of body weight orally and group-2 ponies (5 to 8) were given 0.1 g of indole/kg. Various physical, hematologic, and physiologic measurements were obtained after administration of indole. Intravascular hemolysis and hemoglobinuria were detected in both groups within 24 hours of dosing. Hemolysis was reflected by decreases in PCV, hemoglobin concentration, and RBC count, and an increase in indirect bilirubin. Erythrocyte fragility appeared to increase in both groups at 8 hours after dosing and peaked at 16 hours after dosing. At 72 hours after dosing, the RBC fragility value was less than predose measurements. Heinz body formation was noticed in group-2 ponies, but not in group 1. Plasma indole concentrations increased in both groups from the nondetectable predose concentrations. Group-1 values were 203% of group-2 values. In group 2, plasma indole was nondetectable by 12 hours, whereas low concentrations could still be measured in the group-1 ponies at 24 hours. Ponies in group 1 died or were euthanatized between 24 and 72 hours after dosing, whereas group-2 ponies were euthanatized between 48 and 120 hours. At necropsy, all body fat, mucous membranes, and elastic tissue were stained yellow. Hemoglobinuric nephrosis was the most prominent microscopic lesion. Results of this study indicated that indole, a metabolite of the amino acid tryptophan, causes acute intravascular hemolysis in ponies.

Hematologic reference values were determined for a captive population of 11 Mexican wolves (Canis lupus baileyi). Wolf pups from 4 to 24 weeks old had progressive age-related increases in PCV, hemoglobin concentration, mean cell volume, and RBC counts similar to those seen in domestic dog pups (C familiaris). Hematologic indices in wolves older than 24 weeks were comparable to those of the adult domestic dog; however, PCV, hemoglobin concentration, and RBC counts were higher.

A new topically administered anhydrase inhibitor, MK-927, evaluated for its ocular hypotensive activity in normotensive and glaucomatous Beagles. Single- and multiple-dose studies were performed. Six concentrations of the drug were evaluated in the single-dose study and the 2% solution was used for multiple-dose evaluation. The decrease in intraocular pressure (IOP) was greater in glaucomatous Beagles at the higher concentrations of the drug. The 2 and 4% solutions of MK-927 significantly lowered IOP (mean, 5 mm of Hg; SEM +/- 1.6 and SEM +/- 1.2, respectively) in normotensive and glaucomatous Beagles. In the multiple-dose study, IOP was significantly decreased in the normotensive (mean, 4 mm of Hg; SEM +/- 0.74) and glaucomatous Beagles (mean, 9 mm of Hg; SEM +/- 1.2). The maximal effect was observed by day 4. A contralateral effect was found in glaucomatous Beagles, with the maximal effect on day 4.

Use of microangiography is now essential for the study of microcirculation in various organs. Renal microangiographic studies have been reported in rats, rabbits, dogs, human beings, and mice. However, we could not find any report on use of the technique in cattle, despite high incidence of renal disease in that species. The perfusion technique used in mice was improved over that of our previous report, and was applied to normal and diseased bovine kidneys. For the microangiographic technique, composition of the contrast medium, pressure of the injection, duration of perfusion, and washing of kidneys with heparinized saline solution before perfusion are important. In cattle, 1- to 2-mm-thick sections of the kidneys were generally necessary to observe renal vasculature: arcuate and interlobular arteries, afferent arterioles, and glomerular capillaries. In normal bovine kidneys, the angiographic and microangiographic findings were easily recognized as normal, compared with those of normal mice. In affected bovine kidneys, which histologically represented glomerulonephritis and pyelonephritis, angiography and microangiography revealed corresponding findings.

Oral keratinocytes from dogs were cultured on either collagen gels or artificial matrices at the air-liquid interface, and the expression of keratinocyte antigens and basement membrane components was determined, using various monoclonal and polyclonal antibodies. Keratinocytes grown on collagen gels expressed pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid antigens. Diffuse, suprabasal, and superficial keratinocyte membrane differentiation antigens identified by various monoclonal antibodies also were expressed in a pattern identical to that observed in the native tissue. Laminin and type-IV collagen were deposited at the keratinocyte-collagen interface in a patchy distribution. When synthetic matrices were used, the oral keratinocytes differentiated, but to a lesser extent than cells grown on collagen gels. Antigen expression for cells grown on synthetic matrices was similar to that for cells on collagen, except for failure of the keratinocytes on synthetic membranes to express superficial cell antigens and pemphigus foliaceous antigens.

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Immunoglobulin values were determined in fetal and kitten sera. In the fetal and precolostral kitten sera, only IgG was detected, except in 1 case in which IgM was detected. The IgG, IgA, and IgM were transferred to the kittens through colostrum ingestion with some selectivity. Concentration of the transferred IgG, IgA, and IgM decreased significantly with half-lives of 4.15 +/- 1.29 days, 2.03 +/- 0.33 days, and 2.2 +/- 1.2 days, respectively. As a result of this decrease and increase of de novo immunoglobulin synthesis, IgG, IgA, and IgM were at their lowest values when kittens were 20 to 25 days, 14 to 20 days, and 8 to 10 days old, respectively. After their nadir was reached, IgG values increased gradually, IgA slowly, and IgM rapidly, as a result of de novo immunoglobulin synthesis. When the kittens were 90 days old, their immunoglobulin values were 80% (IgG), 7% (IgA), and 100% (IgM), compared with those of adult cats. These findings suggest that kittens that receive inadequate colostrum from their mothers will be particularly susceptible to infection after they are 5 weeks old.

Pneumonic pasteurellosis was experimentally induced in calves by inoculation of 5 X 10(8) Pasteurella haemolytica organisms into the right diaphragmatic lung lobe. Blood and bronchoalveolar lavage fluid samples were obtained prior to inoculation and at postinoculation hour (PIH) 2, 4, and 6. Calves developed acute lung injury, characteristic of pneumonic pasteurellosis. Lesions were found only in the right diaphragmatic lobe. By PIH 4, significant (P < 0.01) increases were detected in lavage fluid total cell count, neutrophil count, total protein and albumin concentrations, and alkaline phosphatase (ALP) and lactic dehydrogenase (LD) activities. Myeloperoxidase and elastase activities did not increase. Neutrophil depletion ameliorated the lung lesions and prevented the increase in lavage fluid cell count, total protein, and albumin concentrations and ALP and LD activities. Treatment with the iron chelator, deferoxamine mesylatehydroxyethyl starch, attenuated the increase in total protein and albumin concentrations and ALP and LD activities at PID 4, but not PIH 6. Treatment with a neutrophil function inhibitor, pentoxifylline, prevented the increase in lavage fluid neutrophil numbers, but accentuated the increase in total protein and albumin concentrations, and ALP, LD, myeloperoxidase, and elastase activities.