Dynamics of plasma ferulenol concentration and its effect on the vitamin K-dependent coagulation factors, prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined in 4 sheep intoxicated individually with 600 g of powdered Ferula communis variety brevifolia (FCb) given in 8 doses at intervals of 6 hours. Ferulenol was detected in the plasma of all sheep at initial blood sample collection, 6 hours after the first dose of approximately 75 g of FCb was placed in the rumen. The last observed peak of approximately 20 microgram/ml was detected at about 12 hours after the last of 8 doses, and the mean concentration then decreased to < 1 microgram/ml during the next 70 hours. Maximal concentration of ferulenol and time for plasma clearance varied with individual sheep. The PT increased steadily to a maximum of 6 times normal about 70 hours after the last peak plasma ferulenol concentration and about 80 hours after FCb administration was stopped. The PT then retumed to almost normal (ratio of 1.12) from the maximum (ratio of 6.12) within approximately 5 days. The APTT results gnerally paralleled the PT results, but the change was not as marked. Maximal PT and APTT ratios were animal-dependent and not always related to plasma ferulenol concentration. The activity of all the vitamin K-dependent coagulation factors was depressed, but the variations were unique to each factor. Factor V, a vitamin K-independent coagulation factor actually had a brief period of increased plasma activity. We concluded that the effects on PT, APTT, and vitarnin K-dependent coagulation factors induced in sheep intoxicated with FCb were consistent with the coumarinic structure of ferulenol, the intoxicating compound in FCb, which seems to have a short-term anticoagulation effect.

Generation of free radicals and the ability of various antioxidants to attenuate radical production in freshly procured cancellous bone specimens was investigated, using spin-trapping and electron spin resonance (ESR) techniques. Seven core cancellous bone specimens, 10 mm long and 7.9 mm in diameter, were obtained using aseptic technique, from the proximal portion of the humerus of 9 adult mixed-breed dogs. One core cancellous bone specimen from each dog was incubated in spin trap alpha-phenyl-N-tert-butylnitrone in Eagle's minimum essential medium and served as a control. The other 6 specimens from each dog were incubated in alpha-phenyl-N-tert-butylnitrone/Eagle's minimum essential medium plus 1 of the following antioxidants: superoxide dismutase, catalase, superoxide dismutase/catalase, indomethacin, allopurinol, or deferoxamine mesylate. All specimens were incubated at 26 C for 90 minutes, then frozen at -20 C until they were prepared for analysis by ESR spectroscopy. Each specimen was thawed, homogenized, and extracted in a low-dielectric organic solvent prior to obtaining an ESR spectrum which was analyzed for hyperfine splitting constants to identify radicals. Each first-derivative spectrum was digitally double-integrated to obtain an area: these areas were used to compare intensities of the spin. For each treatment group, the areas from the treated specimens were compared with the areas from the control specimens, using a paired t-test. Significance was accepted at P less than or equal to 0.05. Spin adducts were detected in all cancellous bone specimens. Specimens incubated in deferoxamine (P = 0.0017) and superoxide dismutase/catalase (P = 0.0452) had significantly smaller areas than did control specimens. The areas for the other treatment groups did not differ significantly from controls. Our results substantiate free radical production in freshly procured cancellous bone specimens and that radical formation is attenuated by in vitro incubation with deferoxamine or superoxide dismutase/catalase.

Analogues of a melanocyte-stimulating hormone (alpha-MSH) have been documented to be effective in inducing integumental melanogenesis in several species. These melanotropin analogues are more potent than the natural hormone and have prolonged biological activity, without apparent teratogenic or other toxic effects, at least in rodents. In a pilot study, a cyclic alpha-MSH analogue, Ac-[Nle4, Asp5 D-Phe7, Lys10] alpha-MSH4-10-NH2, was administered SC to a dog at a dose of 1 mg of analogue in 1 ml of 0.9% NaCl for 3 weeks, without noticeable adverse effects. There was gradual and extensive darkening of the coat, which originally was predominantly tan, with tips of black. Initially, the darkening involved face and extremities, then gradually expanded to include the trunk and tail hair. Visual pigmentation peaked approximately 2 months after injections were completed. As new hair growth continued subsequent to the injections, the original tan color appeared at the proximal end of the hair shaft, leaving a dark terminal band on all affected hairs. These observations clearly indicated that follicular melanogenesis can be induced in dogs by treatment with a melanotropic peptide.

In a feasability study, a technique for constructing 3-dimensional sonographic images of the superficial digital flexor tendon (SDFT) was established in 6 clinically normal horses and applied to 7 horses with injured SDFT. Two-dimensional B-mode sonographic images were recorded on videotape as the sonographic transducer was manually moved along the palmar aspect of the metacarpal region. Selected videofields were digitized, and 3-dimensional images were constructed, using a computer work station and dedicated software program. The 3-dimensional images were of high quality and presented qualitative clinical information in unique fashion. Indication of the extent of SDFI injuries was excellent. Such 3-dimensional images would be especially useful in explaining to owners and trainers the importance of the injury to their horse and would have a role in monitoring tendon healing and in the assessment of various treatments.

Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (less than or equal to 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P less than or equal to 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 X 103 granulocytes/microliter). In contrast to the toxicoses with body surface area-based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/ m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P S 0.01). This study indicated that a body weight-based (milligram per kilogram) dosing regimen may result in more uniform therapeutic and toxic responses in dogs. Limited toxicosis was observed in dogs weighing > 10 kg treated with doxorubicin with either dosing scheme; however, differences in pharmacokinetic profiles suggested that 1 mg/kg may be an inappropriately low dosage.

Anthelmintic efficacy of doramectin, a macrocyclic lactone of the avermectin family, was evaluated against larval parasitic nematodes in calves. The investigational product was given sc at a dosage of 0.2 mg/kg of body weight to 10 calves infected 6 days previously with third-stage larvae of the genera Haemonchus, Ostertagia, Cooperia, and Nematodirus. Ten additional calves with identical larval exposure were given saline solution SC also at 6 days after inoculation, and served as the nonmedicated controls. At 14 or 15 days after treatment, the calves were slaughtered in complete replicate for nematode recovery and subsequent quantifications. In comparing nematode numbers at necropsy for the saline- and doramectin-treated groups, nematocidal effectiveness as directed against fourth-stage larvae was: 100% for Haemonchus placei and Cooperia spp, > 99% for Ostertagia ostertagi, and 64.5% for Nematodirus helvetianus. All treatments were easily administered, and adverse behavioral or tissue reactions were not seen to result from doramectin administration.

Effects of low-flow ischemia and reperfusion of the large colon on mucosal architecture were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline values. Systemic hemodynamic and metabolic variables were maintained constant and in a normal physiologic range. Full-thickness biopsy specimens were obtained from the left ventral colon for histomorphologic and morphometric examination at baseline and at 30-minute intervals for 6 hours; additional biopsy specimens were collected at 185, 190, and 195 minutes (corresponding to 5-, 10-, and 15-minute periods of reperfusion in group-3 horses). There were no differences among groups at baseline or across time in group-1 horses for any of the histopathologic variables. There were significant (P < 0.05) increases in percentage of surface mucosal disruption, estimated and measured percentage depth of mucosal loss, mucosal hemorrhage, mucosal edema, and cellular debris index during 0 hour to 3 hours, compared with baseline, and from 3 hours to 6 hours, compared with 3 hours in horses of groups 2 and 3. Estimated percentage depth of mucosal loss and cellular debris index were significantly (P < 0.05) greater in group-3 horses, compared with group-2 horses during the interval from 3 to 6 hours. There were trends toward greater percentage of surface mucosal disruption and mucosal edema during the early phase of reperfusion (3 to 4 hours) and greater mucosal hemorrhage, measured percentage depth of mucosal loss, and mucosal interstitial-to-crypt ratio during the late phase (4 to 6 hours) of reperfusion in group-3 horses vs group-2 horses. Reestablishment of colonic arterial blood flow after low-flow ischemia caused greater mucosal injury than did a comparable period of continued ischemia. Thus, reperfusion injury was detected in the large colon of horses after low-flow arterial ischemia. The serial mucosal alterations that developed in the colon were comparable in horses of groups 2 and 3; however, reperfusion exacerbated colonic mucosal injury.

In rats infected with the cestode Taenia taeniaeformis, hepatomegaly results from development of parasitic cysts in the liver. Diffuse nodular mucosal hyperplasia in the glandular region (corpus and antrum) of the stomach, and gross thickening of the intestinal mucosa also result. Between postinfection days (PID) 21 and 84, radiologic observations were made after oral administration of a barium sulfate suspension in T taeniaeformis-infected rats and in age/sex-matched controls. There was radiographic evidence of hepatic enlargement at PID 21. Enlargement of the gastric folds was first observed along the greater curvature of the stomach at PID 35. Fimbriation of small intestinal mucosal surfaces resulted from thickening of the intestinal villi and was observed in the duodenum at PID 21. Intestinal motility was assessed, and contractions were counted, using image intensification fluoroscopy, then were recorded on videotape. There were no significant differences between control and infected rats for gastric emptying time, intestinal transit time, and number of intestinal contractions per minute. Barium contrast radiography clearly indicated large gastric folds, thickening of the small intestinal villi, and hepatic enlargement, and was useful for assessing gastrointestinal motility.

Liposomes and immunostimulating complexes (ISCOM) are adjuvants that have been known to potentiate the immune response to membrane proteins. Adjuvanted outer membrane proteins (OMP) from Salmonella enteritidis were evaluated for their protective efficacy against S enteritidis infection in turkeys. The adjuvanted vaccines prepared for evaluation were: positive or negatively charged liposomes, lipid-conjugated ISCOM, and mineral oil vaccines. These preparations were compared with that of a whole cell bacterin and protein alone. After vaccination, turkeys were challenge-exposed with a nalidixic acid-resistant strain of S enteritidis. They were monitored for clinical signs of disease, antibody response, bacterial shedding pattern, and clearance of the challenge S enteritidis from internal organs. Results indicated a significantly (P < 0.05) higher antibody response to the positively charged liposomal OMP vaccine, compared with the whole cell bacterin. The antibody response to positively charged liposomal OMP vaccine was greater when a booster dose of this preparation was given. Shedding of S enteritidis was decreased in all vaccinated and challenge-exposed turkeys (P < 0.001). The tissues from a high percentage (90 to 100%) of birds that received a booster vaccination of the liposomal (+ or -) and ISCOM vaccine were culture-negative for S enteritidis.

At initiation of a 140-day postweaning weight gain test, Angus bulls were assigned in equal numbers (n = 5) to 1 of 3 treatment groups to determine effects of implantation with zeranol, an estrogenic growth promotant, on selected reproductive characteristics. The bulls, whose age (mean +/- SD) was 233 +/- 20 days at initiation of the test (day 0), were implanted with 36 mg of zeranol on day 0, on days 0 and 60, or were not implanted. At day 140, scrotal circumference and testicular consistency were unaffected by zeranol implantation. Zeranol implantation did not affect the morphologic characteristics of semen samples collected by electroejaculation on day 139. There was no effect of zeranol treatment on paired weights of testes, epididymides, or vesicular glands from bulls at slaughter 47 to 68 days after day 140. Microscopic lesions associated with estrogenic exposure were not observed in accessory sex glands or epididymides of any bull. Histopathologic changes in the seminiferous epithelium were not induced by zeranol treatment. Implantation with zeranol did not affect body weight or hip weight at day 140 or carcass weight at slaughter. Plasma concentration of luteum hormone was increased (P = 0.04), whereas testosterone concentration tended to be less (P = 0.08) in both groups of zeranol-implanted bulls after administration of gonadotropin-releasing hormone on day 140.