Microscopic examination of the nasal mucosa of clinically normal specific-pathogen-free pigs and of toxicogenic type-D Pasteurella multocida toxin challenge-exposed specific-pathogen-free pigs indicated that the surface epithelium in pigs of both groups was microscopically normal; erosions or appreciable inflammatory changes were not evident. In pigs of both groups and in aU 3 regions of the nasal cavity, the endothelial lining of all blood vessels appeared normal without detectable changes to the walls at postinoculation day 10. Vascular injury in the cartilage or the bone was not discernible in control or challenge-exposed pigs. There were marked differences in the osseous structures of the conchae when the 2 groups were compared. In control pigs, active bone formation and remodeling were observed, and the septal cartilage was normal. In toxin challenge-exposed pigs, there likewise was normal bone formation and remodeling in the vestibular region, and the septal cartilage was normal. In marked contrast, conspicuous changes were observed in the osseous core of the conchae of the respiratory and, sometimes, the olfactory regions. These changes consisted of bone necrosis and resorption by large numbers of osteoclasts with variable replacement by dense mesenchymal stroma, which resulted in conchal atrophy. In the absence of any discernible damage or injury (angiopathy) to the nasal vessels, it appears that the action of the dermonecrotoxin of P multocida serotype D is on the most active osteoblasts and the associated organic matrix of the bone, with subsequent disruption of normal bone formation and remodeling of the nasal conchae.

From 2 to 4.5 months of age, 80 crossbred gilts were reared in a conventional grower unit where they were naturally exposed to mycoplasmal and bacterial pathogens that cause pneumonia and atrophic rhinitis. At 4.5 months of age, gilts were moved to environmentally regulated rooms (4.9 X 7.3 m) and assigned at random to 1 of 2 treatment groups: low aerial concentration of ammonia (4 to 12 ppm; mean, 7 ppm) or moderate aerial concentration of ammonia (26 to 45 ppm, mean, 35 ppm). Low concentration of ammonia was obtained by flushing of manure pits weekly, whereas moderate concentration of ammonia was maintained by adding anhydrous ammonia to manure pits that were not flushed. Gilts were weighed biweekly. Mean daily gain (MDG) was less (P < 0.01) for gilts exposed to moderate concentration of ammonia than for gilts exposed to low concentration of ammonia after 2 weeks in their respective environments. By 4 and 6 weeks, however, MDG was similar between the 2 treatment groups. After 6 weeks in these environments, 20 gilts from each treatment group were slaughtered, and prevalence and severity of lung lesions and snout grades were determined. At slaughter, body weight was greater (P < 0.01) in gilts exposed to low, rather than moderate, ammonia concentration (94.5 vs 86.8 kg; SEM, 3.3 kg). Percentage of lung tissue containing lesions (18 vs 12) and snout grade (2.8 vs 3.1) were similar between gilts exposed to low or moderate concentration of ammonia. The remaining 20 gilts in each treatment group were maintained in their respective environments, exposed daily to mature boars and bred at first estrus. Age at puberty was similar between gilts exposed to low or moderate concentration of ammonia (208 vs 205 days; SEM, 1.3 days), even though weight at puberty was less (P < 0.03) for gilts exposed to low concentration of ammonia than for gilts exposed to moderate concentration of ammonia (109.7 vs 118.2 kg; SEM, 4.5 kg).

We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- to 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus IV infusion of Escherichia coli 055:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IGG(T) antibody titer were determined for each foal prior to infusion. A depression index was used to score clinical abnormalities. Serum TNF alpha concentration was estimated by use of an in vitro cytotoxicity bioassay that used WEHI 164 clone 13 cells as targets. The cytotoxic serum factor was identified as TNF alpha by immunoprecipitation with caprine antisera raised against the 15 NH2-terminal amino acids of human TNF alpha. Tumor necrosis factor alpha was not detected in any preinfusion serum samples nor in any samples from foals given saline solution alone. Serum TNF alpha concentration increased in all LPS-infused foals and peaked between 60 and 90 minutes after infusion. Serum TNF alpha concentrations, expressed as mean percentage of peak serum TNF alpha concentration, persisted longer in CD foals given LPS than in CF foals given LPS. All LPS-infused foals displayed clinical signs of endotoxemia, but mean depression index scores of the CF and CD foals given LPS were not significantly different at any time. Serum TNF alpha concentrations were correlated with depression index scores in both LPS-infused groups. Mean rectal temperature increased by 1 hour and remained high for 4 hours after infusion in CF foals given LPS. Mean rectal temperature in CD foals given LPS was significantly less than that for CF foals given LPS 1 and 2 hours after infusion and was higher than mean rectal temperature prior to infusion 3 and 4 hours after.

During the breeding season, the effect of constant administration of an agonist analog of gonadotropin-releasing hormone (GnRH; goserelin acetate) on reproductive activity of mares was determined. Twenty-four mares undergoing estrous cycles were allocated at random to 6 groups (n = 4/group) and, on May 29 (day 0), received no treatment (group 1, controls), 120 micrograms (group 2), 360 micrograms (group 3), 600 micrograms (group 4), or 1,200 micrograms (group 5) of GnRH agonist/d for 28 days via a depot implanted subcutaneously. The final group of mares (group 6) was treated with 120 miocrograms of GnRH agonist/d for 84 days (3 occasions at 28-day intervals). During a pretreatment period (April 19 to May 29) and for 90 days after initiation of GnRH agonist treatment, follicular development and ovulation were monitored by transrectal ultrasonography of the reproductive tract at 2- to 3-day intervals. On each occasion a blood sample was collected for determination of luteinizing hormone (LH) and progesterone. Estrous behavior was monitored by teasing of mares with a stallion. Initiation of agonist treatment was random, relative to the stage of the estrous cycle, and all mares ovulated within 11 days before or after implantation. in 3 of 4 nontreated control mares, estrous cycles were observed throughout the study, with interovulatory intervals ranging from 18 to 26 days. In the remaining mare, concentration of progesterone was high after asynchronous double ovulation during the pretreatment period, suggestive of persistent corpus luteum. In group-2 mares, ovulation occurred in all mares 7 days before and 2 days after initiation of treatment; however, the next anticipated ovulation was delayed in 3 of 4 mares (interovulatory interval, 33 to 70 days). Estrous cycles were not disrupted in the remaining mare. At higher doses (groups 3-5), 1 mare each from groups 3 and 5 ovulated between days 0 and 2 of treatment initiation.

Infectious laryngotracheitis virus (ILTV) is the causative agent of a highly contagious upper respiratory tract infection in chickens. At present, ILTV vaccines are not satisfactory because of development of a latent carrier status in vaccinated birds. Development of recombinant virus vaccines has been hampered by the limited information available on the molecular level and organization of this virus. We isolated 3 assembly intermediates, designated A, B, and C from ILTV-infected cells. Analysis of [3H]thymidine- and [35S]methionine-labeled particles, and electron microscopic studies indicated that particle A was the empty capsid, particle B was the procapsid containing scaffolding protein, and particle C was the DNA-filled capsid. The ILTV procapsids could only be found in the nucleus, which indicated that procapsids could not translocate through the nuclear membrane until they packaged the DNA. The DNA-filled capsids migrated through the nuclear membrane and obtained an envelope from the inner membrane of the nucleus. The enveloped particles then migrated through the lumen of the endoplasmic reticulum into vacuoles in the cytoplasm. Infective virions were isolated from within the infected cells, indicating that budding through the cytoplasmic membrane is not a necessary step in ILTV maturation. Abundant arrays composed of tubules about 45 to 50 nm wide were found in the cytoplasm of chicken embryonic liver cells about 30 to 38 hours after infection. Comparison of the assembly intermediates and the DNA packaging pathway of ILTV with that of bacteriophage phi 29 indicates that similarity exists. A model for the pathway of ILTV assembly is proposed.

Cardiovascular and at accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, PCV, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2, and PaCO2, did not significantly change during the 12 hours of study, PVO2 increased significantly P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time significantly [P < 0.05] starting at 9 hours), despite supplemental IV administered NaHCO3. Plasma concentrations of eicosanoids: 6-ketoprostaglandin F1 alpha (PGF1 alpha, a stable metabolite of PGI2), PGF2 alpha, PGE, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Middle carpal cartilage explants from 4 horses with mild osteoarthritis involving that joint were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan (PSGAG) on proteoglycan synthesis and degradation. Cultures were exposed to 0.025 or 25 mg of PSGAG/ml for 48 hours, after which the medium was replaced with medium containing similar doses of PSGAG and 35S. Subsequently, the sulfated proteoglycan content of the medium and extracts of the explants was measured. Gel filtration chromatography was used to estimate the size and to purify the principal, large proteoglycan monomer, which was further characterized by digestion, using glycosidic enzymes. In a second experiment, explants were incubated with 35S for 48 hours, and were subsequently exposed to the same concentrations of the PSGAG for an additional 48 hours. The amount of remaining labeled proteoglycan was determined for culture medium and cartilage extracts. Gel filtration chromatography was used to assess the hydrodynamic size of the large proteoglycan monomer. Aliquots of proteoglycans from the second experiment were incubated in high-molecular weight hyaluronate and chromatographed to assess reaggregation. Polysulfated glycosaminoglycan caused a significant (P < 0.04) decrease in sulfated proteoglycan synthesis by cartilage explants. Radioactive proteoglycan content in explants labeled prior to exposure to PSGAG were similar. Large proteoglycan monomer size was similar in both experiments (median partition coefficient [K(AV)] = 0.40), and was not influenced by PSGAG treatment. Prelabeled explants exposed to hyaluronate and chromatographed under associative conditions had similar proportions of the radiolabel eluting as proteoglycan aggregate. Enzymatic digestion of newly synthesized large monomer revealed a mild dose-dependent increase in the proportion of keratan sulfate substitution on core protein. It was concluded that PSGAG in vitro, at the dosages evaluated, caused a decre.

Topically administered tissue plasminogen activator (tPA) was evaluated for its penetration into aqueous humor of clinically normal dogs. Two concentrations of tPA (5 mg/ml and 10 mg/ml) were evaluated in a single-dose study, and a concentration of 5 mg of tPA/ml was used for a multiple-dose study. The contralateral eye served as a nontreated control. Enzyme substrate analysis of aqueous humor was used to determine tPA activity. The activity of tPA in aqueous humor was significantly (P < 0.05) greater in treated eyes of all dogs, compared with that in control eyes. Significant differences in activity of tPA were not detected at different doses in treated eyes.

Vaginal aerobic bacterial flora was studied in 5 healthy bitches before, during, and after a 10-day period of treatment with ampicillin and an equally long period of treatment with trimethoprim-sulfamethoxazole. Blood variables and antimicrobial drug susceptibility also were studied. Bacteria were isolated from all bitches before the first treatment period. Bitches from which only a sparse number of bacteria were isolated had flora that varied from day to day. In most instances when bitches were given an antibiotic to which their vaginal bacterial flora was susceptible, these bacteria were eradicated after only 1 day of treatment. This was true for pasteurellae, streptococci, and, in all but one case, Escherichia coli. Staphylococcus intermedius was more difficult to eradicate, and, although susceptible in vitro, it was unaffected by antibiotic treatment in 1 bitch and it took 7 days to eradicate in another. Eradication of aerobic bacteria in the vagina was total only in the bitch that had sparse flora from the beginning. Bacteria colonized within 0 (in 4/5 bitches) to 4 days after termination of treatment with ampicillin and within 0 (in 4/5 bitches) to 3 days for trimethoprim-sulfamethoxazole. Mycoplasmas emerged during and after both treatment periods, and E coli became apparent during treatment with trimethoprim-sulfamethoxazole. Because mycoplasmas may be genital pathogens in bitches and E coli is a common uropathogen, their appearance should be an argument against widespread use of antibiotics in healthy breeding bitches. Two bitches developed a vaginal discharge during treatment or shortly after. Blood variables did not change during the study, nor did antimicrobial drug resistance of the isolated bacteria.

Fifteen isolates of Escherichia coli obtained from the blood and tissues of septic foals had plasmid DNA of size ranging from 2.5 to 93 megadaltons. These isolates grew in normal equine serum (serum resistant), a trait previously documented to be expressed by isolates obtained from blood and tissues of septic foals, but not by isolates obtained from the feces of clinically normal horses. Of these isolates, 3 contained conjugal plasmids that encoded resistance to multiple antimicrobial agents linked to serum resistance and, in 1 isolate, to production of aerobactin as well. Serum resistance and production of aerobactin are related to virulence of septicemic E coli from non-equine sources.