Disposition of ampicillin trihydrate in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle.

The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady-state was significantly higher in lochial fluid (5.27 µg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 µg/mL) compared to milk (0.49 µg/mL) or endometrial tissue (1.55 µg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.

Gastrointestinal nematode infection and performance of weaned stocker calves in response to anthelmintic control strategies.

Gastrointestinal nematode (GIN) parasite control recommendations are in a state of flux because of the increase in anthelmintic resistant cattle parasites, such as Cooperia spp. In addition, Cooperia spp. infection is typically high in warm-season grass pastures and can affect growth performance of grazing stocker calves in the Gulf Coast Region. This study evaluated the effects of moxidectin pour-on, oxfendazole oral suspension, or a combination of the two given at separate times on infection and performance of weaned beef calves grazing summer forages. Steers (n=42) and heifers (n=31) were stratified by sex, d-11 fecal egg count (FEC), and d-1 shrunk body weight (BW) to one of 10 pastures with four anthelmintic treatments and one control. Treatments included: (1) oxfendazole given on d 0 and moxidectin on d 73 (O+M), (2) moxidectin given on d 0 and oxfendazole on d 73 (M+O), (3) moxidectin given on d 0 (M), (4) oxfendazole given on d 0 (O) and (5) no anthelmintic given (CON). Calves grazed for d-110 beginning May 27th. Response variables were FEC (collected on d-11, 14, 31, 45, 59, 73, 87 and 108), coprocultures (evaluated for d 87 and 108), final shrunk BW, shrunk BW gain, average daily gain (ADG), and full BW gain (collected on d 31, 59, 73, 87, and 108). Calves treated with either oxfendazole (O+M and O) or moxidectin (M+O and M) on d 0 had significantly lower (P<0.001) FEC than the CON calves on d 14, 31 and 45. However, the M+O treated calves had significantly higher (P<0.001) FEC than both oxfendazole treated groups. In addition, calves treated with a second dewormer on d 73 (O+M and M+O) had significantly lower (P<0.001) FEC by d 87 than the CON or M treated calves. Shrunk BW gain and ADG were significantly greater (P=0.005) for the O+M compared to the M treated and CON calves, but comparable with the M+O and O treated calves, respectively. Coprocultures sampled on d 87 and 108 for calves not receiving a second dewormer were predominantly Cooperia spp. and Ostertagia spp. On d 87, no larvae were recovered from the M+O treated calves, whereas the O+M treated calves had 94% Cooperia spp. and 3% Ostertagia spp. recovered. Providing a benzimidazole with a macrocyclic lactone given at two different periods may provide better GIN parasite control and improve animal gains for stocker calves grazing warm-season grass pastures.

The effect of various Mycoplasma bovis isolates on bovine leukocyte responses.

Mycoplasma bovis (M. bovis) contributes to a number of clinical syndromes in cattle; in particular, chronic pneumonia that is poorly responsive to therapy has been increasingly recognized as an important cause of morbidity, mortality, and financial loss. M. bovis impairs host immune function, but little is known about whether field isolates vary significantly in their effect on immune function. This research tested the hypothesis that different field isolates vary in their ability to suppress cellular metabolism and cellular production of radical oxygen species (ROS) by bovine leukocytes. Total blood leukocytes from 6 cattle were exposed to six field isolates, two diagnostic lab isolates, and two high passage laboratory isolates of M. bovis, and ROS production was measured by oxidation of dihydrorhodamine 123 (DHR-123). Cellular metabolism was measured by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Significant differences in the response to some field isolates were identified. Three field isolates and both diagnostic lab isolates significantly decreased ROS production by leukocytes from multiple cattle, while the high pass laboratory isolates did not. In contrast, MTT reduction was not significantly impaired by any of the M. bovis strains tested. M. bovis impairs ROS production by bovine leukocytes; the magnitude of the effect appears to be isolate-dependent, and is not related to a general impairment of cellular metabolism. Chronic M. bovis infection in some cattle may be related to impaired ability of leukocytes to produce ROS when exposed to M. bovis.

Evaluation of multiple immune parameters after vaccination with modified live or killed bovine viral diarrhea virus vaccines.

The development of immunity to vaccine antigen was examined using three prime/boost strategies and the progression of immune activities was evaluated over the course of 8 weeks. Calves were vaccinated and multiple immune parameters were evaluated using several methods to assess humoral or cellular immunity from the same samples in parallel. The three vaccination protocols used were a killed vaccine followed by a killed boost (killed/killed), MLV vaccine and boost (MLV/MLV), or a MLV vaccine and killed boost (MLV/killed). All the vaccines used included modified live IBR/PI3 viruses to make the bystander context as similar as possible. The Singer strain of BVDV was used as the source antigen in the killed vaccine, and the NADL strain of BVDV was used in the MLV vaccine. Controls received a vaccine containing only MLV IBR/PI3. The assessment panel measured SN titers, as well as lymphocyte proliferation, cytokine mRNA expression, intracellular cytokine production, and released IFN-gamma after in vitro stimulation with three strains of BVDV virus. MLV/MLV and MLV/killed groups developed significant SN titers to the type 1 BVDV virus strains, Singer and NADL, and low crossover titers were also seen to the type 2 strain, 890 over the evaluation period. These two groups showed significant proliferation in response to the NADL virus as compared to controls. Multiple immune assessments were conducted simultaneously to attempt to provide a broader, more in depth evaluation of immune response to these BVDV vaccination protocols. We observed that the correlation among most of the assays conducted were weak; the correlation between SN titers and cellular proliferation assays demonstrated a moderate correlation.

The role of chemical-induced stress responses in immunosuppression: a review of quantitative associations and cause-effect relationships between chemical-induced stress responses and immunosuppression.

Although there is an increasing awareness that drugs and chemicals can modulate the immune system by indirect mechanisms, few compounds have been thoroughly evaluated in this regard. Several environmentally relevant chemicals induce stresslike responses, as indicated by elevated glucocorticoid levels. Comparable glucocorticoid levels induced by physical or psychological stressors are consistently associated with suppression of one or more immunological parameters. Thus, it seems likely that stress-related neuroendocrine mechanisms are important in immunosuppression by some environmental chemicals. Distinguishing direct and indirect (stress-related) mechanisms of immunosuppression is generally possible, and this could be done as a routine part of immunotoxicity assessment. Although it is clear that glucocorticoids can contribute to such immunosuppression, it is also clear that several other neuroendocrine mediators associated with stress responses can be immunomodulatory. Thus, correlation between glucocorticoid levels and immunosuppression does not conclusively demonstrate a cause-effect relationship. Demonstrating such relationships has been difficult, but it has been done in a few cases of drug-induced thymic hypoplasia by monitoring several parameters known to be affected by glucocorticoids and by measuring the ability of a glucocorticoid antagonist (RU 486) or adrenalectomy to block changes in these parameters. A similar strategy might be useful for evaluation of the role of glucocorticoids in drug- or chemical-induced suppression of a variety of immune functions, but the effects of RU 486 on neuroendocrine feedback circuits and the possibility of consequent immunological changes must be considered when the data are interpreted. This approach could also be applied to evaluation of the roles in chemical-induced immunosuppression of other neuroendocrine mediators for which antagonists or agents that block the synthesis or release of the mediator are available. However, it is likely that a comprehensive (and perhaps predictive) understanding of the relationship between chemically induced stress responses and immunosuppression will require more detailed and quantitative elucidation of the mechanisms and regulation of neuroendocrine-immune interactions.