The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg Of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses. Histochemical (safranin-0) staining intensity was reduced significantly (P < 0.05) in all layers of articular cartilage in MPA-treated joints in groups 1 and 2. In the replacement tissue, intense safranin-O staining was found only in the chondrocyte clusters deep in the tissue of control joints, confirming fibrocartilage repair. Intra-articular administration of MPA in this dosing regimen thus induced degenerative changes in normal articular cartilage and resulted in histomorphologic changes in the repair of full-thickness articular osteochondral defects in horses.

Pigs [9+/-1] weeks old) were inoculated with Streptococcus suis type 2, pseudorabies virus (PRV) or both. For each pig of groups A, B, and C the inoculum of S suis was 10(9) colony-forming units. For each pig of groups A, B, and D the inoculum of PRV was 5 X 10(3) TCID50 of either PRV strain 4892 (group A, n = 9) or PRV isolate B (group B, n = 9). The PRV strain 4892 is a highly virulent strain; isolate B causes mild clinical signs of infection in inoculated pigs. Group-C pigs (n = 9) were given S suis alone, and group-D pigs (n = 3) were inoculated only with PRV isolate B. Clinical signs of infection and development of lesions were readily seen in pigs of groups A, B, and C. Duration and severity of clinical signs of disease and lesions were reduced in pigs of group C, compared with those of the other 2 groups. Lesions, such as polyarthritis and fibrinous pericarditis, were more abundant and acute in the groups of pigs given mixed challenge exposure, compared with pigs inoculated exclusively with S suis type 2 (group C). The group of pigs inoculated with PRV isolate B alone did not manifest clinical signs of disease or lesions. Average daily gain for group-C pigs was higher, compared with that of other groups; the difference was statistically significant at P < 0.02 and P < 0.05 for groups B and D, respectively. Spread of S suis within the tissues of infected pigs was higher in pigs of groups A and B, compared with pigs of group C. Total number of isolations was 8, 15, and 7 for groups A, B, and C, respectively; S suis was isolated from more than 1 tissue specimen from some pigs. The rate of pigs carrying S suis was 4 of 4 in group-A, 7 of 9 in group-B, and 5 of 9 in group-C pigs. It was concluded that clinical disease associated with S suis type 2 was enhanced by concomitant infection with PRV and such effect was common to both PRV strains tested, the highly virulent strain and the strain with low virulence.

Glutamine has been shown to be an important metabolic substrate of enterocytes in many animals, including cats, dogs, hamsters, human beings, monkeys, rabbits, rats, and sheep. To determine whether glutamine is important in the metabolism of cells of the equine gastrointestinal tract, we examined transintestinal differences in glutamine concentrations in the arterial and venous circulation, and measured activity of the major glutamine catabolizing enzyme, glutaminase. Arteriovenous differences provide an index of the amount of a given substrate removed by the tissue across which the measurements are made, and commonly are expressed as a percentage of substrate removed, or percent extraction. Arteriovenous differences for glutamine were determined in 7 anesthetized adult horses (weight, 450 to 500 kg) before and after an IV glutamine infusion. The mean baseline arterial glutamine concentration (+/- SEM) was 572 +/- 24 microM; this concentration quadrupled (to 2,167 +/- 135 microM, P < 0.01) 1 minute after IV bolus infusion of a 17.5-g glutamine load. Baseline extraction by the portal-drained viscera was 7.5 +/- 1.5%; this value increased to 18 +/- 2% at 1 minute (P < 0.01) and had returned to baseline values 60 minutes later. Arteriovenous differences were greatest across the jejunum (11.8 +/- 1.8% in the baseline period vs 33.1 +/- 3.1% at 1 minute, P < 0.001), with smaller differences across the colon, suggesting that the jejunum was the more avid utilizer of glutamine. Glutaminase activity was 4.38 +/- 0.16 and 4.00 +/- 0.60 micromol/mg of protein/h under standard conditions in jejunal and ileal mucosa, respectively. Kinetic studies of jejunal glutaminase revealed the enzyme to have a Km of 3.81 +/- 0.35 mM and a Vmax of 8.08 +/- 0.54 micromol/mg of protein/h, suggesting that the small intestine of horses has a high capacity to extract and metabolize circulating glutamine.

Effect of fluoride was assessed on molars during and after mineralization. Two groups of 7 sheep each were dosed orally with 3.5 mg of fluoride/kg of body weight daily for 4 months (from 5 to 9 months after birth). Sheep of the first group were slaughtered immediately after fluoride administration; those of the second group were slaughtered 4 months later at the age of 13 months. Three control groups of 7 sheep each were slaughtered at 5 months (to determine the state of the teeth at the beginning of fluoride administration), and at 9 and 13 months. During fluoride administration, plasma fluoride concentration rapidly increased to about 0.50 micrograms/ml; after fluoride administration, it stabilized at 0.20 micrograms/ml in treated sheep, whereas controls had concentration of 0.10 micrograms/ml (P < 0.01). Parts of the molars that were in the process of mineralization during fluoride administration (mainly second molars) had thinning enamel, with pits, mainly close to the apex, marked decrease in hardness throughout the layer (< 100 Vickers U, compared with 240 Vickers U), and fluoride accumulation twice as high as that in controls (1,000 to 2,500 mg(kg [dry weight]). Fluoride accumulation was higher in dentine (2,700 to 4,200 mg/kg), but hardness was less affected. On parts of the molars that were already mineralized mostly, the first molar), changes in the appearance of enamel and cementum, decreased hardness (less important than in teeth during mineralization) affecting outer enamel more than inner enamel, high fluoride concentration (4,000 to 5,500 mg(kg [dry weight]) in outer enamel extending over 200 Km were observed. Thus, in sheep, fluoride has a substantial postsecretory effect that may be explained by a slower maturation phase of enamel in this species. Because molar wear is correlated to enamel hardness (dentine at the occlusal surface has low resistance--30 Vickers U), abnormal abrasion of molar teeth that have mineralized before and during fluoride intakes can be observed.

When Salmonella typhimurium and Clostridium perfringens were tested in conventional chickens, larger numbers of S typhimurium and C perfringens adhered to Eimeria tenella-infected ceca than to uninfected ceca. In germ-free chickens, S typhimurium and C perfringens adhered to the E tenella-infected cecal mucosa more than to the uninfected cecal mucosa, but fewer Bacteroides vulgatus and Bifidobacterium thermophilum adhered to the E tenella-infected ceca than to the uninfected ceca. Many bacteria adhered to the lesions caused by E tenella as observed by scanning electron microscopy. On the basis of our findings, we suggest that infection with E tenella upsets the balance of competitive adherence of bacteria, allowing more colonization of S typhimurium and C perfringens.

Immunogenicity of the lipid A component of Haemophilus somnus lipooligosaccharide in cattle and mice was examined after purification, detoxification, and covalent conjugation to a protein carrier. After 2 inoculations, a substantial antibody response was induced in most cattle to lipid A and the protein carrier. To determine whether antibodies to lipid A would be protective, 5 X 10(7) colony-forming units of H somnus strain 649 were administered IV to endotoxin-responsive (C3H/HEN) mice. In one study, 8 of 13 C3H/HEN mice aborted when inoculated. In contrast, abortion did not result when mice were inoculated with the same dose of an isolate of H somnus normally found in the prepuce or with the rough mutant Escherichia coli J5. In addition, endotoxin-nonresponsive (C3H/HeJ) mice were significantly (P = 0.03) more resistant to abortion by strain 649 than were C3H/HeN mice, but inoculated C3H/HeN mice were only slightly more resistant to H somnus abortion, compared with control mice. Although a large antibody response to lipid A was detected, there was no significant difference in the immunized group between mice that aborted and mice that delivered normally. Thus, lipooligosaccharide and other properties of virulent H somnus strains may contribute to abortion in mice.

Sixteen healthy ponies were inoculated IV with Ehrlichia risticii-infected P388D1 mouse monocytes. Of the 16 ponies, 15 developed clinical signs of equine ehrlichial colitis. Twenty-four hours after onset of fever (rectal temperature > 38.8 degrees C), 7 ponies were treated with 25 mg of erythromycin stearate/kg of body weight and 10 mg of rifampin/kg, given orally every 12 hours for 5 days. The remaining 8 ill ponies served as nontreated controls. All ponies were observed for progression of clinical signs typical of equine ehrlichial colitis. Within 12 hours of initiation of treatment, 4 of the 7 treated ponies had rectal temperature < 38.4 C and, within 24 hours, 6 of the 7 ponies had rectal temperature < 38.3C. In contrast, all control ponies had rectal temperature > 39.2 C at 24 hours (P < 0.05). Of the 7 treated ponies, 4 no longer had signs of mental depression after the second day of treatment, and only 1 of the 7 ponies had mild signs of depression after the third day of treatment. In contrast, control ponies had high mental depression score during the observation period (P < 0.05). Feed intake improved in ponies of the treatment group, with feed intake of 4 of the 7 ponies returning to normal; the other 3 ponies were only mildly anorectic by the second day of treatment. Control ponies progressively decreased their feed intake during the observation period (P < 0.05). One control pony and 2 treated ponies developed diarrhea before the treatment/observation period began. Only 1 treated pony developed diarrhea after treatment began. Of the 8 control ponies, 7 developed diarrhea. Profound decrease in borborygmal sounds with silent periods lasting longer than 3 minutes was observed in 7 of the 8 control ponies. Only 1 of the 7 treated ponies had such profound decrease in borborygmi (P < 0.05). The decrease in borborygmal sounds progressed in the control ponies during the observation period. None of the treated ponies continued to have decreased borborygmi after treatment day 2 (P < 0.05). Of the 8 control ponies, 2 were euthanatized; all treated ponies survived. In survivors, signs lasted 8 to 17 (mean, 10) days in control ponies but only 1 to 5 (mean, 2.9) days in treated ponies.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

The anthelmintic efficacy of ivermectin (IVM) delivered from a sustained-release (SR) bolus was evaluated against natural infections with gastrointestinal tract nematodes in 12 crossbred beef heifers in spring. The 12 calves were randomly allotted to 2 groups of 6 calves each. Group-1 calves were treated with an SR bolus designed to deliver 8 mg of ivermectin/d. Group-2 calves were nontreated controls. Cattle groups were kept in separate concrete-floored pens (grass hay nutrition) and slaughter was performed at 35 days after treatment. Fecal egg counts for group-1 calves remained zero after treatment, except for detection of < 1 egg/g of feces in 1 calf at the time of slaughter; counts in nontreated calves increased. Mean and range of Ostertagia ostertagi inhibited larvae in nontreated calves were 27,093 and 10,622 to 56,368, respectively. Efficacy of the IVM SR bolus was 100% against O ostertagi developing fourth-stage larvae (L4) and inhibited early L4, Haemonchus placei adults, Cooperia punctata and C spatulata adult males, Cooperia spp adult females, Cooperia spp L4, Trichostrongylus colubriformis adults, Bunostomum phlebotomum adults, and Oesophagostomum radiatum adults. Efficacy for O ostertagi and T axei adults was 99.9%. Numbers of nontreated calves infected with C pectinata adult males and Oes radiatum L4 were too low to evaluate efficacy. Calves treated with the IVM bolus gained 10.2 kg, whereas nontreated calves lost 1.8 kg. Abomasal lesions were dearly greater in nontreated calves on the basis of index comparisons of abomasal weight and total live weight and gross pathologic features.