Receptors for opsonins, such as complement component C3b (CR1) and immunoglobulins, Fc receptors, interact with adhesion glycoproteins in mediating immune functions. Defects in expression of the adhesion glycoproteins CD11/CD18 results in severely hampered in vitro and in vivo adherence-related functions of leukocytes. Little is known regarding the effect of leukocyte adhesion deficiency (LAD) on ligand binding and receptor expression. We investigated the binding and expression of CR1 and Fc receptors by bovine neutrophils isolated from dairy calves suffering from LAD, compared with clinically normal (hereafter referred to as normal) age-matched calves. Neutrophils were also assayed for endogenously bound IgG and IgM and for exogenous binding of C3b, IgG1, IgG2, IgM, and aggregated IgG (aIgG), using flow cytometry. Luminol-enhanced chemiluminescence (CL) production in response to IgG2 opsonized zymosan was studied, and specific inhibition of CL was used to determine the specificity of IgG2 binding. Activation of protein kinase C with phorbol myristate acetate was used to determine the effect of cellular activation on expression of CR1. A greater percentage of neutrophils from normal calves bound C3b than did neutrophils from LAD-affected calves. Receptor expression was similar. Activation with phorbol myristate acetate resulted in increased expression of CR1 on neutrophils from normal and LAD-affected calves, but expression was almost twofold greater on neutrophils from normal calves. There was no difference between LAD-affected and normal calves in percentage of neutrophils that bound endogenous IgG and IgM. A greater percentage of neutrophils from normal calves bound exogenous IgM than did neutrophils from LAD-affected calves. Receptor expression for aIgG was greater on neutrophils from LAD-affected calves than on those from normal calves.

A study was conducted to investigate whether aspiration of amniotic fluid is associated with a deleterious effect on absorption of colostral immunoglobulins or on blood gas and acid-base values of healthy newborn calves. Fourteen calves purchased from commercial sources were transported to a research facility immediately after birth and fed colostrum with known concentrations of immunoglobulins. Blood samples for gas analyses were collected within 5 hours of birth, 24 hours later, and prior to euthanasia. Between 3 and 5 days of age, calves were euthanatized by an overdose of barbiturates. Eleven calves had evidence of bronchoaspiration of amniotic fluid, as determined by presence of meconium, squamous epithelium, or keratin in histologic sections of fixed lung or by cytologic analysis of bronchoalveolar lavage fluid. Blood gas tensions and pH were within reference ranges in 11 of 14 calves. Aspiration of amniotic fluid could not be linked to any specific changes in blood gas tensions, acid-base status, or absorption of colostral immunoglobulins. Presence of keratin and meconium in the lungs often was accompanied by mild exudative alveolitis and focal atelectasis. It was concluded that aspiration of small amounts of amniotic fluid with or without meconium is common in calves and is not associated with hypoxemia, respiratory acidosis, or failure of passive transfer.

Systemic and pulmonary antibody responses of calves to Pasteurella haemolytica were evaluated by measuring immunoglobulin production in blood for 9 days and in pulmonary lavage fluid for 7 days after intrapulmonary inoculation. Clinical signs, pulmonary lesions, pulmonary and systemic inflammatory response, and amount of antigen in lavage fluid were used to evaluate the response of calves to challenge with P haemolytica. The pulmonary response consisted of production of IgG, IgE, and IgM antibodies to P haemolytica antigens and a 17- to 68-fold increase of cells in lavage fluid 8 hours after inoculation, with a gradual decrease toward normal. Antibodies of the IgM isotype to P haemolytica were demonstrated as early as 8 hours through 7 days after inoculation in 3 of 3 calves. Of the anti-P haemolytica isotypes, IgM was found in the highest concentration. In all of the inoculated calves, IgE was found 1 to 2 days after inoculation, and IgG was found in 2 of 3 inoculated calves from day 1 through 7 after inoculation. Detection of IgG correlated with smaller pulmonary lesions. Immunoglobulin A was not detected in lavage fluid. Serum was evaluated for IgG and IgM antibody response to P haemolytica. Specific IgM was detectable 5 days after inoculation, and IgG was detectable 7 days after inoculation. Pasteurella haemolytica antigens were not detected in serum or plasma. A transient increase in neutrophil count was found 8 hours after inoculation, with return to baseline values by 24 hours after inoculation. Antigen was detected in lavage fluid by use of monoclonal antibodies against selected P haemolytica capsular antigen, outer membrane antigens, and leukotoxin in all inoculated calves 8 hours after inoculation. The monoclonal antibody specific for P haemolytica capsule provided the best detection of antigen. The other monoclonal antibodies detected antigen, but were less consistent.

Pathophysiologic effects of Ostertagia ostertagi infection and their prevention by strategic anthelmintic treatments were studied in 3 groups each of 6 steer calves. Group-1 calves were noninfected controls. Group-2 calves were inoculated with 100,000 third-stage larvae on the 1st and 28th days of the experiment and grazed on pasture initially free of contamination. Group-3 calves were on a similar regimen as those in group 2, but were also treated with ivermectin 9 days after each larval inoculation. Group-2 calves had increased plasma pepsinogen and gastrin values and decreased weight gains, and total serum protein and albumin concentrations from the 2nd week of infection onward. They were anemic at 10 to 12 weeks and had lower carcass and meat quality at slaughter. Strategic anthelmintic treatments were effective in preventing these effects and calves in groups 1 and 3 had similar performances. On the basis of our findings, high pepsinogen values were related to worm burdens, whereas high gastrin concentrations were related to gastric lesions.

The in vivo effects of a single prophylactic dose of recombinant bovine interferon (rBoIFN)-alphaI1 in calves with salmonellosis were investigated, using a Salmonella typhimurium infection model. Treatment with rBoIFN-alphaI1 reduced the degree of septicemia compared with that in control groups, and, in one experiment, using disease of reduced severity, body temperature was lower in treated calves than in controls.

A controlled anthelmintic trial was conducted to determine the efficacy of febantel paste (45.5%) at dosages of 2.5, 5.0, 7.5, and 10.0 mg/kg in calves harboring natural gastrointestinal nematode infections. Dosages of 5.0, 7.5 and 10.0 mg of febantel/kg of body weight were greater than 96% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. The 2.5 mg/kg dosage was considered suboptimal because of low efficacy against Ostertagia and Cooperia spp. Efficacies against Trichostrongylus axei, Trichuris spp, Bunostomum phlebotomum, and Strongyloides papillosus were difficult to determine because fewer numbers of these nematodes were recovered. Efficacies of febantel paste against immature bovine parasites ranged from 83.62% to 97.72%.

Tissue specimens from muscle, liver, kidney, and injection sites were collected, and serum was obtained from 3 calves euthanatized on each of posttreatment days 5 and 22. Calves were treated with 6.7, 13.4, or 20 mg of oxytetracycline (OTC)/kg of body weight, IM, once daily for 3 days; these dosages are 1, 2, and 3 times the label dose, respectively. One control calf was euthanatized on each of posttreatment days 5 and 22. In treated male calves killed 2 days after the last injection, OTC residues were detected in all tissues and serum, using high-performance liquid chromatography. Tissues from all injection sites also were considered positive for antimicrobial residues, using swab test on premises (STOP), microbial inhibition test (MIT), and thin-layer chromatography-biautography (TLCB) test. Kidney tissues from a calf given 13.4 mg of OTC/kg and kidney and liver tissues from a calf given 20 mg of OTC/kg also were considered positive, using the MIT and TLCB. Results of the STOP only were considered positive for the liver and kidney of a calf given 20 mg of OTC/kg, but substitution of Saskatoon antibiotic medium-3 for the original medium (antibiotic medium-5) allowed the STOP to detect residues in these tissues from all treated calves. In female calves killed 19 days after the last injection, the STOP, MIT, and TLCB procedures revealed positive results for tissues from some injection sites, but revealed negative results for other tissues. High-performance liquid chromatographic analyses detected OTC in tissues from injection sites from all treated calves, in muscle and liver from a calf given 20 mg of OTC/kg, and in kidneys from calves given 13.4 or 20 mg of OTC/kg. The STOP, MIT, and TLCB procedures lacked the sensitivity of high-performance liquid chromatography for detection of OTC residues.

The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharamacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case. Twice daily oral dosing at 20 mg/kg should reduce the plasma peak:trough ratio and provide plasma concentrations more cnsistently within the human therapeutic range of 10 to 20 micrograms/ml. Even then, therapeutic drug monitoring should be done.