Over a 24-month period, serum tumor necrosis factor (TNF) activity was determined in 289 horses with colic attributable to gastrointestinal tract disease. Serum TNF activity was quantitated by use of a modified in vitro cytotoxicity bioassay, using WEHI 164 clone-13 murine fibrosarcoma cells. Causes for colic, determined by clinical and laboratory evaluation, exploratory celiotomy, or necropsy included: gastrointestinal tract rupture (GTR); ileal impaction; small intestinal strangulating obstruction (SIO); proximal enteritis (PE); transient small intestinal distention; large-colon displacement; large-colon vovulus; large-colon impaction; colitis; small-colon obstruction; peritonitis; and unknown. Each diagnosis was placed into 1 of 3 lesion categories: inflammatory disorders (GTR, PE, colitis, peritonitis); strangulating intestinal obstruction (SIO, large-colon volvulus); and nonstrangulating intestinal obstruction (ileal impaction, transient small intestinal distension, large-colon displacement, large-colon impaction, small-colon obstruction, unknown). The prevalence of high serum TNF activity and/or mortality were evaluated. Differences were tested at significance level of P < 0.05. Approximately 20% of the 289 horses has serum TNF activity greater than that found in clinically normal horses (> 2.5 U/ml). Twenty-three horses (8%) had marked increase in serum TNF activity (greater than or equal to 10 U/ml) which was more prevalent among horses with SIO and PE than in horses of other diagnostic groups, except those with GTR. Mortality and marked increase in serum TNF activity were greater in horses with intestinal inflammatory disorders or strangulating intestinal obstruction than in horses with nonstrangulating intestinal obstruction. Similarly, a greater proportion of the horses that died had markedly high serum TNF activity than did horses that lived. Mortality of horses with serum TNF greater than or equal to 10 U/ml was greater than that of horses with serum TNF activity < 10 U/ml. Results indicate possible association between colic and serum TNF activity in horses and that high mortality may be associated with horses with markedly increased serum TNF activity.

Thirty-seven local isolates of Actinobacillus suis-like organisms from diseased and clinically normal horses and 1 Ilama were compared with reference strains of A suis, A lignieresii, A equuli, A capsulatus, A hominis, A (Pasteurella) ureae, and equine A suis-like organisms (ASLO) previously described in literature. Comparison was by cultural characteristics, carbohydrate fermentation, enzyme profiles, and whole-cell protein polyacrylamide gel electrophoresis. Carbohydrate fermentation, determined by API-CH gallery, divided 36 equine ASLO isolates into 6 API-CH biotypes. The Ilama isolate was an additional distinct biotype. The biochemical comparisons between A suis and ASLO did not reveal remarkable and consistent differences. Enzyme analysis revealed 5 API-ZYM biotypes, one of which included the same strains as one of the API-CH biotypes and consisted in both instances of 4 esculin-negative ASLO cultures and the reference strain of A lignieresii. We conclude that the 4 strains were hemolytic variants of A lignieresii. Protein electrophoresis disclosed 15 banding patterns, 10 of which represented equine ASLO strains. The reference strains of A suis shared the pattern predominant among equine ASLO. Four of the remaining reference strains of Actinobacillus species each had a unique profile, whereas the type strain of A capsulatus and the Ilama isolate had similar profiles. The groupings of cultures resulting from the different testing methods had little relation to each other and to the anatomic source of the strains except the strains comprising API-CH biotype III, which originated in the equine respiratory tract, and the A lignieressi cluster.

Biological responses to recombinant DNA-derived bovine interferon alpha (rBoIFN-alpha I1) by bovine alveolar macrophages were examined by measuring viral yield reduction and 2',5'-oligoadenylate synthetase (2',5'-OAS) production by IFN-treated cells. In vitro IFN pretreatment of alveolar macrophages reduced viral yield in cultures challenged exposed with parainfluenza-3 virus, compared with control cultures. In vitro treatment of alveolar macrophages with IFN also resulted in increased 2',5'-OAS activity. The 2',5'-OAS activity was measured in alveolar macrophages and blood mononuclear leukocytes of calves injected im with 3.6 X 10(6) U of rBoIFN-alpha I1/kg of body weight. The IFN action was monitored by measuring 2',5'-OAS activity of blood mononuclear leukocytes beginning 6 days before and ending 24 hours after IFN treatment. The 2',5'-OAS activity in the blood mononuclear leukocytes sharply increased 24 hours after IFN treatment, indicating response to IFN. The alveolar macrophages collected from the same calves 24 hours after IFN administration also had increased 2',5'-OAS activity, compared with alveolar macrophages from the same calves collected 6 days before treatment. Increased 2',5'-OAS activity indicates: a possible mechanism of IFN action in cattle that may be responsible for viral yield reduction; potential use of high enzyme activity as a marker for IFN induction; and potential use of 2',5'-OAS activity as a marker for determining effects of IFN on bovine macrophages and other cells of the bovine immune system.

We evaluated the efficacy of acyclovir against experimentally induced herpesvirus infection (Pacheco's parrot disease) in Quaker parakeets. Thirty-two of 40 birds were challenge-exposed with 0.1 ml of a suspension of herpes-virus (10(4) median cell culture infective doses CCID50 ) given IM. Treatment with acyclovir was started 24 hours later and was continued for 7 days. The birds were allotted to 5 groups of 8 birds each. There was a considerable difference in mortality between groups 1-5. Of 8 birds in each group, 6 died in group 1 (control), 1 died in group 2 (gavage), 3 died in group 3 (low dose, IM), 4 died in group 4 (high dose, IM), and none died in group 5 (contact controls). There was a significant (P = 0.023) difference in mortality between groups 1 and 2, thus the oral form of acyclovir administered by gavage was the most efficacious therapeutic regimen. Clinical signs and death occurred after discontinuation of acyclovir in groups 2 and 3, whereas the mean time of death for the control group was 6 days after challenge exposure. Herpesvirus was recovered by inoculation of chick embryo cell culture with pooled tissue suspensions from all birds that died. Histologic evidence of herpesvirus infection was found in most birds that died, with the control group having the most severe lesions. Surviving Quaker parakeets were transferred to cages with seronegative Quaker parakeets with no known exposure to herpesvirus. There have been no deaths attributable to herpesvirus infection in a period exceeding 2 years.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,.

In these studies, the effects of recombinant human interleukin 2 (rHuIL-2) were examined on in vitro tumor cytotoxicity by canine blood lymphocytes obtained from peripheral vessels through use of a chromium release microcytotoxicity assay. Cytotoxic activity by lymphokine-activated killer cells was significantly increased, compared with that by untreated lymphocytes in a dose-dependent manner. The maximal effect was attained with 300,000 IU of rHuIL-2/ml. Lymphokine-activated killing also was dependent on the duration of incubation with rHuIL-2. After 1 day of rHuIL-2 incubation, cytotoxicity was significantly increased, compared with that of untreated lymphocytes. Of the 3 times examined, cytotoxicity peaked after 3 days of rHuIL-2 incubation. High levels of cytotoxic activity were still present at 7 days of incubation. Numbers of granular lymphocytes increased over the times examined. These results demonstrate functional and morphologic changes in canine peripheral blood lymphocytes obtained from peripheral vessels after incubation with rHuIL-2 in a dose- and time-dependent manner.

Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed feed, was added to the diets of growing wethers (mean body weight, 34.0 kg) and was evaluated for its ability to diminish the clinical signs of aflatoxicosis. The experimental design consisted of 4 treatment groups of 5 wethers each, consuming concentrations of 0 g of HSCAS and 0 g of aflatoxin (AF)/kg of feed (control; group 1); 20 g of HSCAS/kg (2.0%; group 2), 2.6 mg of AF/kg (group 3); or 20 g of HSCAS (2.0%) plus 2.6 mg of AF/kg (group 4). Wethers were maintained in indoor pens, with feed and water available ad libitum for 42 days. Lambs were observed twice daily and weighed weekly, and blood samples were obtained every 2 weeks for hematologic and serum biochemical analyses and for measurement of mitogen-induced lymphocyte-stimulation index. At the termination of the study, wethers were euthanatized and necropsied. Body weight gain was diminished significantly (P less than 0.05) by consumption of 2.6 mg of AF/kg of feed, whereas body weight of lambs consuming HSCAS plus AF did not differ from that of control wethers. The AF-alone treatment increased serum aspartate transaminase and gamma-glutamyltransferase activities, prothrombin time, and cholesterol, uric acid, and triglyceride values and decreased albumin, glucose, and urea nitrogen values, and urea-to-creatine ratio. A 27% decrease in lymphocyte stimulation index, increased spleen weight (as a percentage of body weight), and decreased liver weight were induced by AF-alone treatment. Results indicate that HSCAS may be a high-affinity sorbent for AF, that 2.6 mg of AF/kg of feed induces signs of aflatoxicosis in growing wethers, that lambs may not be as resistant to the effects of AF as previously thought, that 2.0% HSCAS can substantially reduce the toxic effects of 2.6 mg of AF/kg, and that sorbent compounds may offer a novel approach to the preventive management of aflatoxicosis in livestock.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

Previous studies of the amino acid analogue, alpha-ketoisocaproate (KIC), indicate that it can stimulate lymphocyte blastogenesis and antibody responses of sheep. To determine whether KIC could overcome the effects of adreno-corticotropic hormone (ACTH)-induced lymphocyte suppression, 24 lambs were fed a control diet, a diet supplemented with 0.05% KIC, or a diet supplemented with 0.05% of the parent amino acid leucine. Immune status was monitored by determining lymphocyte blastogenic responsiveness to phytohemagglutinin-P (PHA), concanavalin A (conA), and pokeweed mitogen (PWM) and percentages of T-cell subsets in the blood, using monoclonal antibodies and a flow cytometer. Serum cortisol, insulin, and glucagon concentrations also were determined. After 60 days of consuming the respective diet, lambs were administered either saline solution or ACTH (100 IU) twice daily for 3 consecutive days. Administration of ACTH increased serum cortisol and insulin concentrations; however, no effects were seen for serum glucagon concentration. Compared with saline administration, ACTH administration significantly (P < 0.05) suppressed mitogen-stimulated lymphocyte blastogenesis by approximately 50%, regardless of the mitogen used, and significantly (P < 0.01) decreased the percentage of circulating T lymphocytes and decreased (P < 0.01) the ratio of T4 to T8 cells. Lambs fed KIC had greater PHA- and conA-stimulated blastogenic responses and significantly (P < 0.05) increased ratio of T4 to T8 cells in the blood, compared with lambs fed the leucine-supplemented diet or the control diet and given corresponding injections. These data indicate that ACTH decreased in vitro lymphocyte blastogenesis and altered the subset ratios of blood lymphocytes in sheep. These changes were partially prevented by feeding KIC.

Cortical bone screws were implanted into the proximal portion of the right and left radius and ulna of 6 newborn Quarter Horse foals as radiographic markers for measurement of growth. Distance between markers on a lateral radiographic view was measured. Radiographs were taken at 2-week intervals until the horses were 8 weeks old, at 4-week intervals until they were 48 weeks old, and at 12-week intervals until they were 72 weeks old. The proximal radius and ulna grew at similar rates during the 72-week period of evaluation, and growth continued throughout 72 weeks. The proximal radius grew 3.5 cm, and the ulna grew 3.4 cm. Although the rates of growth were similar, growth from the ulnar physis contributed only to the length of the olecranon; growth was not transmitted to the ulnar diaphysis distal to the cubital joint. The proximal radius slid distally in relation to the ulna as growth occurred at the proximal radial physis. These findings suggest that transfixing the ulna to the radius while growth is occurring at the proximal radial physis impedes the natural shifting process, and subluxation of the elbow can result. Severity of subluxation would be inversely related to the age of the horse at the time of transfixation.