Larry C. Hollis

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.

Comparison of iatrogenic transmission of Anaplasma marginale in Holstein steers via needle and needle-free injection techniques

OBJECTIVE To compare iatrogenic transmission of Anaplasma marginale during sham vaccination between needle and needle-free injection techniques. ANIMALS 26 Holstein steers confirmed negative for anaplasmosis by use of a competitive ELISA (cELISA) and an A marginale-specific reverse transcription (RT)-PCR assay. PROCEDURES An isolate of A marginale was propagated to a circulating parasitemia of 2.0% in a splenectomized steer. Sham vaccination was performed in the left cervical muscles of the splenectomized parasitemic steer with a hypodermic needle fitted to a multiple-dose syringe. The same needle and syringe were used to sham vaccinate a naïve steer. This 2-step procedure was repeated until 10 naïve steers (group ND) were injected. Similarly, sham vaccination of the left cervical muscles of the splenectomized parasitemic steer and another group of 10 naïve steers (group NF) was performed by use of a needle-free injection system. Five control steers were not injected. Disease status was evaluated twice weekly for 61 days by use of light microscopy, a cELISA, and an A marginale-specific RT-PCR assay. RESULTS Iatrogenic transmission was detected in 6 of 10 steers in group ND. Disease status did not change in the NF or control steers. Sensitivity of light microscopy, cELISA, and RT-PCR assay was 100% on days 41, 41, and 20 after sham vaccination, respectively; however, only cELISA and RT-PCR assay sustained a sensitivity of 100% thereafter. CONCLUSIONS AND CLINICAL RELEVANCE Needle-free injection was superior to needle injection for the control of iatrogenic transmission of A marginale.

Biocontainment, biosecurity, and security practices in beef feedyards

OBJECTIVE To determine the biocontainment, biosecurity, and security practices at beef feedyards in the Central Plains of the United States. DESIGN Survey. SAMPLE POPULATION Managers of feedyards in Colorado, Kansas, Nebraska, Oklahoma, and Texas that feed beef cattle for finish before slaughter; feedyards had to have an active concentrated animal feeding operation permit with a 1-time capacity of >or= 1,000 cattle. PROCEDURES A voluntary survey of feedyard personnel was conducted. Identified feedyard personnel were interviewed and responses regarding facility design, security, employees, disease preparedness, feedstuffs, hospital or treatment systems, sanitation, cattle sources, handling of sick cattle, and disposal of carcasses were collected in a database questionnaire. RESULTS The survey was conducted for 106 feedyards with a 1-time capacity that ranged from 1,300 to 125,000 cattle. Feedyards in general did not have high implementation of biocontainment, biosecurity, or security practices. Smaller feedyards were, in general, less likely to use good practices than were larger feedyards. CONCLUSIONS AND CLINICAL RELEVANCE Results of the survey provided standard practices for biocontainment, biosecurity, and security in feedyards located in Central Plains states. Information gained from the survey results can be used by consulting veterinarians and feedyard managers as a basis for discussion and to target training efforts.

Sodium salicylate treatment in early lactation increases whole-lactation milk and milk fat yield in mature dairy cows

Multiple lines of inquiry have suggested that a high degree of inflammation in early lactation cows is associated with low productivity and increased disease incidence. In addition, some small studies have suggested that milk production increases in response to antiinflammatory treatment in the first week of lactation. Our objective was to determine if administration of sodium salicylate (SS), a nonsteroidal antiinflammatory drug (NSAID), in the first week of lactation changes whole-lactation productivity and retention in the herd. At calving, 78 cows [n=39 primiparous (1P); n=24 second parity (2P); n=15 third parity or greater (3P)] were alternately assigned to either control (CON) or SS treatments for 7 d postpartum. Sodium salicylate treatment was administered via individual water bowls at a concentration of 1.95 g/L, delivering a mean of 123.3±5.5 g of salicylate/d during the 7-d treatment. For the first 21 d of lactation, dry matter intake, water intake, milk yield, and health were monitored daily, and milk samples were collected twice weekly for milk component analysis. Monthly milk yield and component testing through the rest of the lactation provided data to assess long-term responses, and the effects of treatment on the risk of leaving the herd and on 305-d milk, fat, and protein yields were assessed. During the first 21 d of lactation, we observed no differences in morbidity, except for increased risk of metritis in 3P SS cows. Treatment interacted with parity to influence both 305-d milk and milk fat yields, and a tendency for an interaction was detected for 305-d milk protein yield. Milk yield was 2,469±646 kg greater over the lactation in 3P SS cows compared with 3P CON cows (21% increase) and tended to decrease by 8% in 1P cows treated with SS; no effects were detected in 2P cows. Furthermore, 3P SS cows produced 130±23 kg more milk fat over the lactation (30% increase), with no effects detected for 1P or 2P. Treatment with SS tended to increase 305-d milk protein yield in 3P cows by 14%, with no effects in 1P or 2P cows. A tendency for a treatment × parity interaction was also observed for the risk of leaving the herd. First-parity cows treated with SS tended to have greater risk of leaving the herd than controls (30 vs. 6% risk); however, treatment did not alter herd retention in 2P or 3P groups, and SS had no effect on the risk of leaving the herd overall. Results indicate that SS has long-term effects on lactation of mature dairy cows, particularly on fat yield, but may have negative effects for primiparous cows.

Potential associations between fecal shedding of Salmonella in feedlot cattle treated for apparent respiratory disease and subsequent adverse health outcomes

A prospective cohort study was used to assess whether Salmonella fecal shedding in commercial feedlot cattle treated with antimicrobials for respiratory disease was associated with subsequent adverse health outcomes. Feces were collected per rectum from cattle that were examined for apparent respiratory disease, had a rectal temperature ≥40 °C, and subsequently received antimicrobial treatment. Salmonella were recovered from 918 (73.7%) of 1 245 fecal samples and weekly prevalence estimates ranged from 49 to 100% over the 3-month study. Genotypic and phenotypic characteristics of Salmonella strains in the population were determined. Serogroup E Salmonella were most common (73.3%), followed by C1 (11.0%), C3 (8.6%), and B (1.1%). Predominant serotypes were Orion (46.5%), Anatum (19.8%), Kentucky (8.7%), Montevideo (7.5%), and Senftenberg (4.9%). Few isolates (36/918) were positive for antimicrobial resistance-associated integron gene intI1. Phenotypic susceptibility was associated with isolate intI1 status. Crude re-pull, re-treatment and case fatality risks were higher for cattle that were Salmonella-positive versus -negative at initial treatment, but not statistically different on multivariable analysis. However, case fatality risk was higher for cattle shedding Group B Salmonella than for cattle shedding other serogroups. Lots (groups) with a higher Salmonella prevalence at first treatment had a higher proportion of mortalities occur in a hospital pen, higher overall re-treatment risks, and were more likely to be sampled later in the study. Results indicate a high prevalence of Salmonella in this population of cattle treated for apparent respiratory disease, but that effects associated with clinical outcomes may depend on the Salmonella strain.

The efficacy of three chlortetracycline regimens in the treatment of persistent Anaplasma marginale infection.

Chemosterilization is reported in cattle fed chlortetracycline hydrochloride (CTC) at dosages ranging from 1.1mg/kg for 120 days to 11 mg/kg for 30-60 days. The relationship between plasma CTC drug concentration and carrier clearance has not been described. Chronic carrier status was established in 21 steers with a Virginia isolate of Anaplasma marginale and confirmed by cELISA and an A. marginale-specific RT-PCR. Four negative, splenectomized steers served as active disease transmission sentinels. Steers were randomized to receive 4.4 mg/kg/day (LD); 11 mg/kg/day (MD); or 22 mg/kg/day (HD) of oral chlortetracycline; or placebo (CONTROL) for 80 days. The LD, MD and HD treatment groups consisted of 5 infected steers and 1 splenectomized steer; CONTROL group had six infected steers and 1 splenectomized steer. The daily treatments and ration were divided equally and fed twice daily. Blood samples were collected semi-weekly for determining plasma drug concentration by ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry method and assessment of disease status by both cELISA and RT-PCR. Mean (CV%) chlortetracycline plasma drug concentrations in the LD, MD, and HD groups were 85.3 (28%), 214.5 (32%) and 518.9 (40%)ng/mL during days 4 through 53 of treatment. A negative RT-PCR assay result was confirmed in all CTC-treated groups within 49 days of treatment; however, cELISA required an additional 49 to 88 days before similar results. Subinoculation of splenectomized steers confirmed chemosterilization. These results are important for influencing future chemosterilization strategies and impacting free trade policy among countries and regions of contrasting endemicity.

Microbial translocation of needle-free versus traditional needle injection-enhanced beef strip loins.

Our objective was to determine the effects of needle-free (NF) versus needle injection (N) enhancement on microbial translocation of generic Escherichia coli in beef strip loins. Fifteen longissimus muscles (LM) were obtained and halved. Surfaces were inoculated with generic E. coli at a level of 10(6) CFU/cm(2) (three replications of five strip loins). LM halves were injection-enhanced with a phosphate and salt solution with either NF or N injection. After injection, two cores were taken from each LM half and sliced cross-sectionally at depths of 2-mm (surface), 1, 3, and 5 cm. The paired samples were stomached, serially diluted, and plated. Surface samples from N-injected muscles had lower (P<0.05) E. coli counts (2.79 versus 3.23 log CFU/g for NF). Also, the 3- and 5-cm depth samples from N injection had the least (P<0.05) E. coli contamination (1.69 versus 2.12 CFU/g for NF). Although traditional N injection resulted in approximately 0.5 log CFU/g less microbial contamination at all depths, because the level of contamination was extremely high, the difference in the treatments could arguably be of little practical importance in terms of safety.

Hot topic: Early postpartum treatment of commercial dairy cows with nonsteroidal antiinflammatory drugs increases whole-lactation milk yield

Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36 h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125 g/cow per day; SAL); (2) 1 bolus of meloxicam (675 mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, β-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365 d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365 d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers.

Plasma pharmacokinetics of oral chlortetracycline in group fed, ruminating, Holstein steers in a feedlot setting

Chlortetracycline HCl (CTC) has impacted profitable livestock production since 1945. However, pharmacokinetic parameters for CTC in ruminating cattle are unavailable in peer-reviewed literature. A total of 18 steers were randomized to 4.4, 11, or 22 mg/kg/day p.o. CTC treatment groups (n = 6). Chlortetracycline treatment was offered as one-half of the daily dose b.i.d. (160 total doses/group) for 80 days. Blood samples were collected at selected time points throughout an 83-day study and analyzed with a solid phase extraction technique and novel ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy analytical method. Noncompartmental analysis (NCA) determined individual pharmacokinetic parameters by treatment group with coefficient of variation (CV %) estimates. A one-compartment open model with first order absorption and elimination, where absorption rate constant was equal to elimination rate constant, was fitted using nonlinear mixed effects modeling (NLMEM). NLMEM determined the primary pharmacokinetic parameters: volume of distribution (V/F, 40.9 L/kg) and rate constant (k, 0.0478 h(-1)), and the secondary parameters: dose-normalized area under the curve (AUC/D, 0.29 h x microg/L), clearance (Cl/F, 1.8 L/kg/h), elimination half-life (t(1/2), 16.2 h), C(max/Dose) (4.5 ng/mL), and time of C(max) (T(max), 23.3 h) with improved CV estimates over NCA. Dose linearity was confirmed by anova of parameters derived from NCA by treatment group. Further studies are necessary for determining absolute bioavailability and pharmacokinetic-pharmacodynamic relationships of CTC in group fed, ruminating cattle.

Incidence and severity of Arcanobacterium pyogenes injection site abscesses with needle or needle-free injection

Nursery-age pigs (n=198) were used to evaluate the difference in abscess formation at needle-free jet and conventional needle-and-syringe injection sites. Needle-free jet injection was used to administer injections in the neck and ham on one side of the animal whereas needle-and-syringe was used for neck and ham injections on the opposite side. Immediately prior to injection, the injection site surfaces were contaminated with an inoculum of Arcanobacterium pyogenes. Each pig was humanely euthanized 27 or 28 days after injections. Histopathological results showed that needle-free jet injection was associated with more abscesses than needle-and-syringe injection at both neck (P=0.0625) and ham (P=0.0313) injection sites. Out of 792 injection sites, only 13 abscesses were observed, with 12 of those present at needle-free jet injection sites. Needle-free jet injection may increase the occurrence of injection site abscesses that necessitate carcass trimming at pork processing plants.