In this study, 20 young steers received no beta-adrenergic agonist (C), 100 animals all received zilpaterol hydrochloride, with 1 group only receiving zilpaterol (Z) while the other 4 groups received zilpaterol and vitamin D3 at the following levels and durations before slaughter: 7 million IU Vit D3 /animal/day for 3 days (3D7M); 7 million IU Vit D3/animal/day for 6 days (6D7M); 7 million IU Vit D3/animal/day for six days with 7 days no supplementation (6D7M7N) and 1 million IU Vit D3/animal/day for 9 days (9D1M). Left carcass sides were electrically stimulated (ES) and the right side not electrically stimulated (NES). Samples were aged for 3 or 14 days post mortem. Parameters included Warner Bratzler shear force (WBSF), myofibril filament length (MFL), sarcomere length and calpastatin and calpain enzyme activities. For drip loss and instrumental colour measurements, samples were analysed fresh (1 day post mortem) or vacuum-aged for 14 days post mortem. Both ES-treatment and prolonged aging reduced WBSF (P < 0.001). Treatments 6D7M, 6D7M7N and Z remained significantly tougher than C (P < 0.001), while 3D7M and 9D1M improved WBSF under NES conditions. ES was shown to be more effective at alleviating beta-adrenergic agonist induced toughness than high vitamin D3 supplementation. Aging increased drip loss, lightness, redness and yellowness while ES increased drip loss. In general, Z showed increased drip loss, lighter meat, and reduced redness. Vitamin D3 supplementation could not consistently overcome the adverse effects of zilpaterol hydrochloride in feedlot steers. / Thesis (PhD)--University of Pretoria, 2012. / Animal and Wildlife Sciences / unrestricted

Master of Science / Department of Animal Sciences and Industry / James S. Drouillard / Exogenous growth promotants, such as the synthetic beta agonist zilpaterol hydrochloride (ZH), have been shown to increase carcass weight by repartitioning energy toward increased skeletal muscle at the expense of adipose tissue, which is associated with a decline in tenderness. More recently, essential oils such as menthol have been observed to have growth promoting properties in livestock. The objectives of this research were to determine effects of ZH on blood parameters and long chain fatty acids in plasma and adipose tissue, to determine if the decline in tenderness can be negated by temporary depletion of calcium during ZH supplementation, and to determine effects of crystalline menthol on blood parameters. Blood samples were collected in 7-d intervals during ZH administration. Zilpaterol hydrochloride decreased concentrations of plasma urea nitrogen and whole blood glucose (P < 0.10), but had no effects on concentrations of plasma glucose, lactate, beta-hydroxybutyrate, NEFA, or whole blood lactate (P > 0.10). Total long chain fatty acids of plasma and adipose tissue were unaffected (P > 0.10); however, ZH supplementation increased HCW, dressing percentage, and LM area (P < 0.10). Calcium was temporarily depleted during ZH supplementation in an attempt to increase tenderness of meat. No differences (P > 0.10) were observed for Warner-Bratzler shear force values, live animal performance, or carcass measurements. Addition of 0, 0.003, 0.03, 0.3% menthol (diet DM) to diets of steers resulted in a menthol × time within day interaction (P < 0.01) for IGF-1 concentration and BW; however, glucose, lactate, and PUN concentrations were unaffected (P > 0.05). Furthermore, concentrations of VFA were not different (P > 0.05), but production of fermentative gas was decreased (P < 0.01) when menthol was added at 0, 0.003, 0.03, 0.3% of substrate DM in a 24 h in vitro fermentation trial. Results from these studies suggest ZH improved efficiency of nutrient utilization for increased skeletal muscle growth; however, the decline in tenderness was not negated by the temporary depletion of calcium in the diet. Overall, ZH affected components related to increased skeletal muscle growth, but menthol did not affect blood parameters associated with growth.

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Daniel U. Thomson / Beta-adrenergic agonists (βAA) are administered during the final weeks of the beef production system to improve efficiency and increase meat yield. Welfare concerns linked to the administration of βAA have garnered significant attention in recent years due to anecdotal reports of increased mortality during βAA feeding periods and cattle without obvious disease or injury having difficulty walking at abattoirs being overrepresented in cattle fed βAA. Thomson et al. (2015) reported 2 events where cattle were distressed, became non-responsive to handling, sloughed hoof walls and were euthanized while in lairage at the abattoir. Consistent blood abnormalities in euthanized cattle included elevated blood lactate (25.6 mmol/L; ref. range: < 4-5) and creatine kinase (CK; 6,890 U/L, ref. range: 159- 332). Although no causal relationship had been established, dialogues among groups of packers, animal scientists, and welfare experts implicating the βAA zilpaterol hydrochloride (ZIL; Zilmax®, Merck Animal Health, Desoto, KS) as one possible etiology resulted in a major beef packer announcing plans to stop accepting cattle fed ZIL. Consequently, Merck announced a self-imposed suspension of ZIL sales in U.S. and Canadian markets until further research could be conducted to investigate the manner. Utilization of technologies such as βAA are imperative to meeting the demands of a growing world population and verdicts regarding such technologies, including their impact on animal welfare, should be based on scientific merit. The first objective of this research was to evaluate the effect of shade on performance and animal well-being in cattle fed ZIL. The second objective was to characterize the clinical description and hematological profile of fatigued cattle presented to abattoirs. The third objective was to evaluate the effects of handling intensity during shipment for slaughter in cattle fed a βAA. The fourth objective was to evaluate the effects of βAA administration on performance and physiological response to different handling intensities during shipping for slaughter. Shade provision reduced open-mouth breathing and increased dry matter intake and dressing percentage. Fatigued cattle observed at abattoirs had increased respiratory rates and muscle tremors, although blood parameters were relatively normal compared to their cohorts. Metabolic acidosis, a precursor for Fatigued Cattle Syndrome, was observed in cattle exposed to aggressive handling regardless of βAA status. This research confirms the improved growth performance of cattle fed βAA and highlights the improvement of animal welfare through shade provision and low-stress handling in heavy-weight feedlot cattle.

Doctor of Philosophy / Department of Animal Sciences and Industry / John A. Unruh / Sixty cows were utilized to investigate the use of zilpaterol, implanting, and concentrate feeding on performance, carcass traits, subprimal yield, steak retail display, and meat palatability of cows fed for 70 d. The 5 treatments were: 1) grass-fed on pasture (Grass); 2) concentrate-fed (C); 3) concentrate-fed and implanted (CI) with a trenbolone acetate/estradiol implant, DE); 4) concentrate-fed and fed zilpaterol beginning on d 38 of the feeding period (CZ); and 5) concentrate-fed, implanted and fed zilpaterol (CIZ). Hot carcass weights and dressing percentages were higher (P < 0.05) for all concentrate-fed cows than grass-fed cows. The CIZ cows had the largest and grass-fed cows the smallest longissimus muscle (LM) areas. Total subprimal weights were lightest for cuts from the grass-fed cows; and CIZ cows had greater weights than those from C cows. Sensory panelists found LM steaks from C and grass-fed cows were more tender than steaks from CZ and CIZ cows; and steaks from CI cows were more tender than steaks from CIZ cows. However, no tenderness differences were observed among treatments for knuckle (KN) steaks. In another study, carcasses from 31 fed cows and 24 fed steers were used to investigate the effects of aging (7 or 28 d) on LM retail display; aging and enhancement (blade tenderization and enhancement solution injection) on LM tenderness; and aging on enhanced KN, top blade, and top sirloin steaks. Steaks (LM) aged 7 d had less discoloration and were more color stable than steaks aged for 28 d. A sensory panel found enhanced-cow LM steaks were more tender than non-enhanced steaks; and aging for 28 d improved tenderness compared to 7 d aging for non-enhanced steaks only. Aging for 28 d compared to 7 d improved Warner-Bratzler shear (more tender) for enhanced cow top sirloin, steer top sirloin, and steer top blade steaks. Feeding cull cows a concentrate diet improved lean meat yields. When feeding a concentrate diet a combination of an implant and feeding zilpaterol can further increase lean meat yields. Enhancement provides an opportunity to improve tenderness of steaks from fed cows and steers.

McMaster University MASTER OF SCIENCE (2019) Hamilton, Ontario (Medical Sciences) TITLE: Modulation of cyclic adenosine monophosphate for potentiation of long-acting β2-agonist and glucocorticoids in human airway epithelial cells AUTHOR: Yechan Kim, B.HSc. (McMaster University) SUPERVISOR: Dr. Jeremy Alexander Hirota NUMBER OF PAGES: xiv, 81 / In Canada, asthma is the third most common chronic disease resulting in 250 premature deaths annually and related healthcare expenses exceeding $2.1 billion/year. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Despite an advanced understanding on how to treat and manage the symptoms of asthma, current therapy is sub-optimal in 35-50% of moderate-severe asthmatics around the world resulting in lung inflammation, persistent impairment of lung function, and increased risk of mortality. Combination of long-acting β2 agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma. Increasing intracellular cyclic adenosine monophosphate (cAMP) beyond existing combination LABA/GCS are likely to be beneficial for the management of difficult to control asthmatics that are hypo-responsive to mainstay therapy. In human airway epithelial cells (HAEC), cAMP is either exported by transporters or broken down by enzymes, such as phosphodiesterase 4 (PDE4). We have demonstrated that HAEC express ATP Binding Cassette Transporter C4 (ABCC4), an extracellular cAMP transporter. We also show that ABCC4 and PDE4 inhibition can potentiate LABA/GCS anti-inflammatory responses in a human epithelial cell line in a cAMP-dependent mechanism validating the pursuit of novel ABCC4 inhibitors as a cAMP elevating agent for asthma. / Thesis / Master of Science in Medical Sciences (MSMS) / Asthma is a common chronic lung disease characterized by narrow and inflamed airways that cause breathing difficulties. Current management includes the combination of bronchodilators, to relax the airway, and steroids, to decrease inflammation. Unfortunately, this combination therapy is suboptimal in 35-50% of users, increasing the risk of asthma attacks, hospitalization rate, and health care costs. Recently, there have been studies theorizing that we can improve the therapy’s ability to decrease inflammation by increasing cAMP, an important molecule for biological activities. We tested this claim by blocking the breakdown and export of cAMP to increase its levels and measured inflammatory cytokines, molecules that direct the action of immune cells. Our results show that in a model of viral infection, administering the combination therapy while increasing cAMP levels can further decrease inflammatory cytokines prompting further investigation for its potential implication in the clinic.