A field trial comparing four oral nonsteroidal anti-inflammatory drugs on controlling cautery dehorning pain and stress in calves.

The purpose of this study was to compare the analgesic effect of four nonsteroidal anti-inflammatory drugs (NSAIDs) administered as a single, standardized, oral dose in dairy calves at the time of cautery dehorning. The NSAIDs investigated have pharmacokinetic properties in cattle that produce persistent plasma concentrations that may provide prolonged analgesia with the added practicality of a simple administration regimen. One hundred and eighty-five Holstein calves aged approximately 50 d old were either sham dehorned (n = 31) or cautery dehorned following oral administration of carprofen (n = 31), firocoxib (n = 31), flunixin meglumine (n = 30), meloxicam (n = 31) or placebo (n = 31) in a randomized, controlled trial. A standard dose of 2.0 mg/kg was administered to all calves receiving an oral NSAID. All calves received local anesthesia prior to actual or sham dehorning. Cortisol concentrations, heart rate, mechanical nociception thresholds, ocular and dehorning area temperatures, and average daily gains were evaluated. A linear mixed-effects model with repeated measures was used for statistical analysis. Administration of oral meloxicam, flunixin meglumine, and firocoxib at 2.0 mg/kg resulted in decreased cortisol concentrations compared to placebo-treated controls for the first 24 h postdehorning (AUEC0-24) (P = 0.03). Moreover, firocoxib, flunixin meglumine, and meloxicam attenuated the maximum cortisol concentrations compared to placebo-treated calves (P = 0.04, P= 0.02). In calves treated with flunixin meglumine, cortisol concentrations was reduced at 4 h (P = 0.04) and 8 h (P = 0.02). In addition, analgesic administration was associated with changes in ocular and dehorning area temperature differences (P = 0.09). Carprofen and meloxicam reduced heart rates during the entire study period (P = 0.003). Although a treatment effect (P < 0.0001) was observed in the determination of mechanical nociception threshold among all treatment groups, meloxicam expressed marginally significant effects (P = 0.09) among NSAID treated groups dehorned. A single dose of oral meloxicam, flunixin meglumine, or firocoxib administered at 2.0 mg/kg reduced the acute stress response associated with cautery dehorning. However, carprofen administration was associated with increased cortisol concentrations and dehorning area temperatures for the initial 24 h. Given the changes in pain and stress outcome variables assessed in this study, NSAIDs should be administered at the time of dehorning.

An Update on the Assessment and Management of Pain Associated with Lameness in Cattle.

Lameness affects the cattle industry via both economic losses and welfare considerations. In addition to production deficits, the pain and distress associated with lameness have been documented. Evaluation and prevalence of lame cattle are among the primary factors in third-party welfare audit programs. Mean lameness prevalence in herds has been reported to be as high as 36.8%, although a less than 10% prevalence of lame cattle was reported by some producers. Note that lameness is usually underreported by producers compared with independent observers, potentially because of a decreased sensitivity in detecting lame cattle.

Clinical pharmacology of analgesic drugs in cattle.

Providing pain relief in cattle is challenging. In the absence of labeled drugs, the Animal Medicinal Drug Use Clarification Act regulates the extralabel drug use of analgesics in cattle within the United States. Given the variety of pharmacokinetic and pharmacodynamic properties of pain-relieving drugs, evidence needs to drive the development of analgesic protocols for cattle during pain-related events. This article reviews the commonly used analgesics investigated in cattle including local anesthetics, nonsteroidal anti-inflammatory drugs, opioids, α2-agonists, N-methyl-d-aspartate receptor antagonists, and gabapentin. These compounds are examined with respect to evidence of analgesia in cattle during pain states.

Genetic diseases conferring resistance to infectious diseases.

This review considers available evidence for mechanisms of conferred adaptive advantages in the face of specific infectious diseases. In short, we explore a number of genetic conditions, which carry some benefits in adverse circumstances including exposure to infectious agents. The examples discussed are conditions known to result in resistance to a specific infectious disease, or have been proposed as being associated with resistance to various infectious diseases. These infectious disease-genetic disorder pairings include malaria and hemoglobinopathies, cholera and cystic fibrosis, tuberculosis and Tay-Sachs disease, mycotic abortions and phenylketonuria, infection by enveloped viruses and disorders of glycosylation, infection by filoviruses and Niemann-Pick C1 disease, as well as rabies and myasthenia gravis. We also discuss two genetic conditions that lead to infectious disease hypersusceptibility, although we did not cover the large number of immunologic defects leading to infectious disease hypersusceptibilities. Four of the resistance-associated pairings (malaria/hemogloginopathies, cholera/cystic fibrosis, tuberculosis/Tay-Sachs, and mycotic abortions/phenylketonuria) appear to be a result of selection pressures in geographic regions in which the specific infectious agent is endemic. The other pairings do not appear to be based on selection pressure and instead may be serendipitous. Nonetheless, research investigating these relationships may lead to treatment options for the aforementioned diseases by exploiting established mechanisms between genetically affected cells and infectious organisms. This may prove invaluable as a starting point for research in the case of diseases that currently have no reliably curative treatments, e.g., HIV, rabies, and Ebola.

Impact of transmammary-delivered meloxicam on biomarkers of pain and distress in piglets after castration and tail docking.

To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT). Ten sows received either meloxicam (30 mg/kg) (n = 5) or whey protein (placebo) (n = 5) in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean) meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2) synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059). There was a time-by-treatment interaction for plasma cortisol (p = 0.0009), with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67). Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015). This study demonstrates the successful transfer of meloxicam from sows to piglets through milk and corresponding analgesia after processing, as evidenced by a decrease in cortisol and PGE2 levels and maintenance of cranial skin temperature.

Salmonella as a biological "Trojan horse" for neoplasia: future possibilities including brain cancer.

This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a "Trojan horse" for future oral biotherapy of brain cancer.

Antibiotics acting as neuroprotectants via mechanisms independent of their anti-infective activities.

This review considers available evidence that some antibiotics have ancillary neuroprotective effects. Notably, ß-lactam antibiotics are believed to increase the expression of glutamate transporter GLT1, potentially relieving the neurological excitotoxicity that characterizes disorders like amyotrophic lateral sclerosis. Minocycline has shown promise in reducing the severity of a number of neurological diseases, including multiple sclerosis, most likely by reducing apoptosis and the expression of inflammatory mediators in the brain. Rapamycin inhibits the activity of a serine/threonine protein kinase that has a role in the pathogenesis of numerous neurologic diseases. Herein we examine the unique neuroprotective aspects of these drugs originally developed as anti-infective agents.

Pharmacokinetics of intravenously and orally administered meloxicam in sheep.

OBJECTIVE: To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep. ANIMALS: 6 healthy adult Dorset cross sheep (5 males and 1 female). PROCEDURES: Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods. RESULTS: Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 µg/mL (1.45 to 1.93 µg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.

Bovine dehorning: assessing pain and providing analgesic management.

Dehorning or disbudding in cattle is performed for a variety of reasons using various methods. Pain associated with this procedure has been mostly evaluated through behavioral, physiologic, and neuroendocrine changes following dehorning. Analgesics, including local nerve blockades, anti-inflammatories, and opioids have demonstrated an effective attenuation of the cortisol response. The administration of sedatives with analgesic properties has been indicated in the attenuation of the acute phase of pain associated with dehorning. Following a literature review, this article recommends a multimodal approach to analgesia for dehorning procedures, including the use of a local anesthetic and anti-inflammatory and, when possible, a sedative-analgesic.

Assessment and management of pain associated with lameness in cattle.

Lameness impacts the cattle industry in economic losses and welfare considerations. In addition to production deficits, pain and distress associated with lameness have been documented. The evaluation and prevalence of lame cattle is one of the primary factors in third-party welfare audit programs. To improve earlier detection and treatment of lameness, locomotion scoring systems have been developed for routine use by farm employees. Recommendations for pain management typically include the use of a multimodal therapeutic approach. Similarly, in lame cattle, pain can best be alleviated by implementing a multimodal approach including corrective claw trimming and placement of foot blocks combined with additional benefits provided by analgesic compounds.

Disseminated hemangiosarcoma in a cow.

An antemortem diagnosis of disseminated hemangiosarcoma with extensive hepatic and splenic involvement was made in a 9-year-old cow evaluated for lethargy, weight loss, regenerative anemia, thrombocytopenia, and elevated liver enzymes. This is the first report of hemangiosarcoma in a cow with a suspected primary location of the liver and/or spleen.