Mineral composition of serially slaughtered Holstein steers supplemented with zilpaterol hydrochloride.

Calf-fed Holstein steers (n = 115; 449 ± 20 kg) were utilized in a serial harvest experiment. A baseline group of five steers was harvested after 226 d on feed (DOF), which was designated day 0. The remaining cattle were assigned randomly to 11 harvest groups, with slaughter every 28 d. Cattle were either not (CON) or were fed zilpaterol hydrochloride for 20 d followed by a 3 d withdrawal (ZH). There were five steers per treatment in each slaughter group ranging from days 28 to 308. Whole carcasses were divided into lean, bone, internal cavity, hide, and fat trim components. Apparent mineral retention (Ca, P, Mg, K, and S) within the body was calculated as the difference between mineral concentration at slaughter and day 0. Mineral concentration at day 0 was determined from body composition of steers harvested at day 0 multiplied by individual live body weight (BW) at day 0. All data were analyzed as a 2 × 11 factorial arrangement with individual animal as the experimental unit. Orthogonal contrasts were used to analyze linear and quadratic contrasts over time (11 slaughter dates). There were no differences in concentration of Ca, P, and Mg in bone tissue as feeding duration increased (P ≥ 0.89); concentration of K, Mg, and S in lean tissue did fluctuate across DOF (P < 0.01). Averaged across treatment and DOF, 99% of Ca, 92% of P, 78% of Mg, and 23% of S present in the body were in bone tissue; 67% of K and 49% of S were in lean tissue. Expressed as gram per day, apparent retention of all minerals decreased linearly across DOF (P < 0.01). Expressed relative to empty body weight (EBW) gain, apparent Ca, P, and K retention decreased linearly as BW increased (P < 0.01) whereas Mg and S increased linearly (P < 0.01). Apparent retention of Ca was greater for CON cattle (greater bone fraction) and apparent retention of K was greater for ZH cattle (greater muscle fraction) when expressed relative to EBW gain (P ≤ 0.02), demonstrating the increase in lean gain by ZH cattle. There were no differences in apparent retention of Ca, P, Mg, K, or S due to treatment (P ≥ 0.14) or time (P ≥ 0.11) when expressed relative to protein gain. Apparent retention averaged 14.4 g Ca, 7.5 g P, 0.45 g Mg, 1.3 g K, and 1.0 g S/100 g protein gain. Expressing apparent mineral retention on a protein gain basis minimized effects of rate and type of gain, allowing for better comparison across treatments and time. Feeding zilpaterol hydrochloride did not affect apparent mineral retention when expressed relative to protein gain.

Mineral requirements for feedlot cattle are largely based on measured mineral concentration in the body at harvest. Fairly extensive research has been done quantifying Ca and P in the body of cattle, but data on Mg, K, and S are sparse. Serial harvest experiments are expensive and labor intensive and therefore not conducted frequently. A group of 115 Holstein steers was fed a finishing diet with serial harvest every 28 d. Two treatments were evaluated, control and cattle fed zilpaterol hydrochloride to increase lean tissue growth. Every 28 d, five steers from each treatment group were harvested with the whole carcass divided into lean, bone, internal cavity, hide, and fat trim components. Apparent mineral retention was calculated as the difference between mineral composition at day 0 (baseline harvest group) and each 28 d harvest group. Averaged across treatment and days on feed, 99% of Ca, 92% of P, 78% of Mg, and 23% of S present in the body were measured in bone tissue; 67% of K and 49% of S were in lean tissue. Apparent retention averaged 14.4 g Ca, 7.5 g P, 0.45 g Mg, 1.3 g K, and 1.0 g S/100 g protein gain.

Transcriptome analyses indicate that heat stress-induced inflammation in white adipose tissue and oxidative stress in skeletal muscle is partially moderated by zilpaterol supplementation in beef cattle.

Heat stress (HS) triggers oxidative stress, systemic inflammation, and disrupts growth efficiency of livestock. ß-adrenergic agonists supplemented to ruminant livestock improve growth performance, increase skeletal muscle mass, and decrease carcass fat. The objective of this study was to understand the independent and interacting effects of HS and zilpaterol hydrochloride (ZH) supplementation on the transcriptome of subcutaneous white adipose tissue and the longissimus dorsi muscle in steers. Twenty-four Red Angus-based steers were assigned to thermoneutral (TN; Temperature Humidity Index [THI] = 68) or HS (THI = 73-85) conditions and were not supplemented or supplemented with ZH (8.33 mg/kg/d) for 21 d in a 2 × 2 factorial. Steers in the TN condition were pair-fed to the average daily feed intake of HS steers. RNA was isolated from adipose tissue and skeletal muscle samples collected via biopsy on 3, 10, and 21 d and sequenced using 3' Tag-Seq to an achieved average depth of 3.6 million reads/sample. Transcripts, mapped to ARS-UCD1.2, were quantified. Differential expression (DE) analyses were performed in DESeq2 with a significance threshold for false discovery rate of 0.05. In adipose, 4 loci (MISP3, APOL6, SLC25A4, and S100A12) were DE due to ZH on day 3, and 2 (RRAD, ALB) were DE due to the interaction of HS and ZH on day 10 (Padj < 0.05). In muscle, 40 loci (including TENM4 and OAZ1) were DE due to ZH on day 10, and 6 loci (HIF1A, LOC101903734, PDZD9, HNRNPU, MTUS1, and TMCO6) were DE due to environment on day 21 (Padj < 0.05). To explore biological pathways altered by environment, supplement, and their interaction, loci with DE (Praw < 0.05) were evaluated in Ingenuity Pathway Analysis. In adipose, 509 pathways were predicted to be altered (P < 0.01): 202 due to HS, 126 due to ZH, and 181 due to the interaction; these included inflammatory pathways predicted to be upregulated due to HS but downregulated due to the interaction of HS and ZH. In muscle, 113 pathways were predicted to be altered (P < 0.01): 23 due to HS, 66 due to ZH, and 24 due to the interaction of HS and ZH. Loci and pathway data in muscle suggest HS induced oxidative stress and that the stress response was moderated by ZH. Metabolic pathways were predicted to be altered due to HS, ZH, and their interaction in both tissues. These data provide evidence that HS and ZH interact to alter expression of genes in metabolic and immune function pathways and that ZH moderates some adverse effects of HS.

Heat stress (HS) negatively impacts livestock health and carcass quality. Supplementation of livestock with ß-adrenergic agonists (ß-AA) increases muscle mass and decreases fat deposition. The purpose of this study was to understand how HS and zilpaterol hydrochloride (ZH), a ß-AA, alter gene expression in muscle and in adipose of cattle. Twenty-four steers were assigned to thermoneutral (TN) or HS conditions and were not supplemented (NS) or supplemented with ZH for 21 d. RNA was isolated from muscle and adipose collected on days 3, 10, and 21 to identify changes in gene expression. Several individual loci were differentially expressed (DE) due to HS or ZH in both tissues while the interaction of HS and ZH altered expression in adipose. A less stringent definition of DE used to explore biological pathways predicted that both treatments alter metabolism. Pathway analyses also supported that HS increased inflammation in adipose, but that these inflammatory pathways were downregulated by ZH. HS also was predicted to induce oxidative stress in muscle although ZH moderated this response. This study provides information on how HS and ß-AA act independently and interact to alter physiology, lending insight useful for the development of management and mitigation strategies for stress.

Muscle fiber morphometry and physicochemical characteristics of the Longissimus thoracis muscle of hair male lambs fed zilpaterol hydrochloride and implanted with steroids.

Muscle fiber morphometry and physicochemical characteristics were evaluated in LT muscles obtained from entire male lambs treated with zilpaterol hydrochloride (ZH, 0 and 0.15 mg/kg body weight) and/or steroidal implant (SI, with and without trenbolone acetate/estradiol). ZH and SI acted synergistically to increase LT area, type-IIb fiber cross-sectional area and soluble collagen content, likewise to decrease metmyoglobin concentration and insoluble collagen content. Ash content and ultimate pH showed a decrease due to an antagonistic effect between ZH and SI. Content of total collagen, protein, fat, moisture, oxidized lipids and water-holding capacity were unaffected by ZH and SI. Supplemental ZH, but not SI, decreased all color parameters and tended to increase shear force. Overall, the SI implantation of male lambs followed by a ZH supplementation promoted greater LT hypertrophy, without affecting protein and fat content, and physicochemical characteristics in their meat.

Zilpaterol hydrochloride lowers marbling score by dilution of marbling and depression of intramuscular adipocyte volume in M. longissimus dorsi of beef steers.

We hypothesized that zilpaterol hydrochloride (ZH) depresses marbling scores in beef cattle by dilution of the intramuscular (i.m.) adipose tissue in the longissimus thoracis (LT) by increased muscle cross-sectional area. Crossbred steers were treated with ractopamine hydrochloride (RH; 28 d) or ZH (20 d) or no ß-adrenergic agonist (CON). ZH increased LT cross-sectional area (P < .001) and depressed rib fat depth (P < .001), USDA marbling score (P < .05), percent LT lipid (P < .02), total lipid in a 2.54 cm-thick LM steak (P < .05) and most LT lipid fatty acids (P ≤ .05),but had no effect on mean i.m. adipocyte volume (P = .15). ZH increased the relative volume proportion of smaller i.m. adipocytes (250 to 500 pL) and decreased the proportion of larger i.m. adipocytes (2000 and 3000 pL) (P < .05). We conclude that ZH reduces marbling score both by dilution of the marbling and a depression of i.m. adipocyte relative volumes.

Growth, carcass characteristics, cut yields and meat quality of lambs finished with zilpaterol hydrochloride and steroid implant.

Forty hairbreed male lambs were used to evaluate the effects of zilpaterol hydrochloride (ZH, 0 and 0.15 mg/kg BW) and steroid implant (SI, without and with 52.5 mg trenbolone acetate and 7.5 mg 17ß-estradiol) on feedlot performance, carcass characteristics, non-carcass components, wholesale cut yield, and meat quality. Supplemental ZH increased growth rate, feed efficiency, carcass weight, and dressing percentage, with no effect on wholesale cut yields. Feeding ZH increased muscle pH at 24 h. Supplemental ZH increased meat shear force, but decreased lightness, redness, and yellowness after frozen storage followed by a 14-day aging period. The SI administration increased dressing percentage and neck yield, but decreased testicle weight and meat redness, without affecting other variables. The LT area was greater with ZH + SI administration than with individual application of ZH or SI. Compared to individual administration, simultaneous application of ZH and SI did not result in improved growth performance, carcass traits and wholesale cut yields in hairbreed male lambs.

Carcass fabrication yields of beef steers supplemented zilpaterol hydrochloride and offered ad libitum or maintenance energy intake.

An experiment was conducted to evaluate the fabrication yields of carcasses from beef steers supplemented zilpaterol hydrochloride (ZH) and fed at maintenance (MA) or ad libitum (AB) intake levels. Beef steers (n = 56) from a common sire were blocked (n = 28 per block) by terminal growth implant and sorted into pairs by BW. Four pairs (n = 8) were harvested on day 0; the remaining 24 pairs (n = 48) were assigned to a dietary intake level (MA or AB) and days on feed (28 or 56 d). Within pairs of MA or AB intakes, steers harvested on day 56 were randomly assigned to supplementation of ZH (90 mg·d-1 per steer) for 20 d followed by a withdrawal period of 4 d or control (C). Steers (BW = 603.5 ± 48.1 kg) were harvested at a commercial processing facility. After a 24-h chill period, standard USDA grading procedures were used to derive a calculated yield grade and quality grade. Following grading, left carcass sides were transported to the West Texas A&M University Meat Laboratory for fabrication. Each side was fabricated into subprimals to determine individual red meat yield (RMY), trimmable fat yield (TFY), and bone yield (BY). A mixed model was used for analysis; fixed effects included treatment combinations and random effects included block and pairs. Single df contrasts tested day 0 vs. 28, day 0 vs. 56, day 28 vs. 56, MA vs. AB, and C vs. ZH. Yield of chuck eye roll differed (P = 0.05) by days on feed (0 d = 4.14, 28 d = 4.11, 56 d = 4.55%). Similarly, eye of round yield was impacted (P = 0.02) by days on feed (0 d = 1.51, 28 d = 1.37, 56 d = 1.36%). Additionally, brisket yield was altered (P < 0.01) by days on feed (0 d = 4.08, 28 d = 3.56, 56 d = 3.48%) and treatment (C = 3.34, ZH = 3.61%). For remaining subprimals, no differences (P ≥ 0.15) were detected. Furthermore, results indicated that RMY tended (P = 0.07) to differ by treatment (C = 61.35, ZH = 63.67%). Comparatively, TFY was impacted (P = 0.04) by intake (MA = 20.44, AB = 23.33%). Results from this study indicate that a MA intake level during the last 56 d of the finishing period concurrent with ZH supplementation impacts subprimal yields as well as carcass RMY and TFY of beef steers.

Profiling the Nucleobase and Structure Selectivity of Anticancer Drugs and other DNA Alkylating Agents by RNA Sequencing.

Drugs that covalently modify DNA are components of most chemotherapy regimens, often serving as first-line treatments. Classically, the reactivity and selectivity of DNA alkylating agents has been determined in vitro with short oligonucleotides. A statistically sound analysis of sequence preferences of alkylating agents is untenable with serial analysis methods because of the combinatorial explosion of sequence possibilities. Next-generation sequencing (NGS) is ideally suited for the broad characterization of sequence or structure selectivities because it analyzes many sequences at once. Herein, NGS is used to report on the chemoselectivity of alkylating agents on RNA and this technology is applied to the previously uncharacterized alkylating agent trimethylsilyl diazomethane.

Live growth performance, carcass grading characteristics, and harvest yields of beef steers supplemented zilpaterol hydrochloride and offered ad libitum or maintenance energy intake.

A trial was conducted to examine live growth efficiency, harvest yields, and carcass grading performance of steers fed at maintenance (M) or at ad libitum (A) level of intake during zilpaterol hydrochloride (Z) supplementation. Single-sired, beef steers (n = 56; start of trial BW 590 ± 36 kg) blocked (n = 2) by weight and terminal implant were sorted into pairs (n = 14 per block) by weight. Pairs of steers were initially assigned to 0, 28, or 56 d of feeding. Within 28 or 56 d, pairs were assigned to M or A intake. Steers within a pair assigned to 56 d of feeding were randomly assigned to either 20 d of Z supplementation (90 mg/d per steer) with a 4 d withdrawal period prior to slaughter or to no ZH supplementation (C). Steers were housed and fed in individual pens. Weights of all non-carcass and carcass components were recorded at slaughter; carcasses were graded 24-h postmortem. Data were analyzed via a mixed model; the fixed effect was treatment combination with random effects of block and pair. Live growth data used harvest day as the repeated measure and animal as the subject. Single df contrasts were constructed for day 0 vs. day 28, day 0 vs. day 56, day 28 vs. day 56, M vs. A, and C vs. Z. Treatment impacted (P ≤ 0.05) live ADG; contrasts indicated A (1.33) was greater than M (0.14 kg), and Z (1.12) was greater than C (0.82 kg). Similarly, carcass ADG differences (P < 0.01) indicated A (1.04) was greater than M (0.36 kg), and Z (1.35) was greater than C (0.71 kg). Intake level altered BW and empty body weight (EBW); M cattle had reduced BW and EBW (P < 0.01, 585 and 540 kg) than A cattle (647 and 597 kg). Cattle fed at M had less carcass and internal cavity mass (P < 0.01, 359 and 79.4 kg) than A cattle (394 and 93.5 kg). Liver mass was reduced by M feeding (P < 0.01; M-5.03, A-6.69 kg) and Z treatment (P < 0.01; Z-5.64, C-6.06 kg). Moreover, mass of total splanchnic tissue was less (P < 0.01) for M cattle than A cattle (59.8 vs. 72.5 kg). Dressed carcass yield was greater (P < 0.01) for Z than C cattle (63.5 vs. 61.6%). Cattle fed at M had less 12th rib s.c. fat, lower numerical U.S. yield grades (P < 0.01; M-1.71 cm and 3.3, A-2.46 cm and 4.3) and lower numerical Canadian yield grades (P < 0.01; 51.9 vs. 53.9% for M and A, respectively) than A cattle. Results indicate that energy intake level and Z supplementation influence live and carcass growth, carcass transfer, kill yields, and carcass characteristics across time.

Evaluation of Commercial ß-Agonists, Dietary Protein, and Shade on Fecal Shedding of Escherichia coli O157:H7 from Feedlot Cattle.

Escherichia coli O157:H7 is a foodborne pathogen commonly associated with cattle feces. Diet, including dietary supplements such as ß-agonists, may impact fecal shedding of this pathogen. A series of three experiments were conducted to determine if the ß-agonists ractopamine hydrochloride (RAC) or zilpaterol hydrochloride (ZH) would impact the level or prevalence of fecal E. coli O157:H7 shedding. In Experiment 1, dietary RAC did not impact fecal shedding of E. coli O157:H7 based on the level or prevalence, but the addition of dietary soybean meal (SBM) in the study did reduce E. coli O157:H7 shedding. In Experiments 2 and 3, dietary ZH did not affect fecal E. coli O157:H7 shedding as determined by enumeration or prevalence, but in Experiment 2 the addition of 30% (dry matter basis) wet distillers grains with solubles (WDGS) in the diet tended to increase E. coli O157:H7 shedding. Shade is a potential management tool to reduce heat stress in cattle, and in Experiment 3 the presence of shade over the feedlot pens did not affect E. coli O157:H7 shedding. The use of ß-agonists in cattle diets did not significantly affect fecal shedding of E. coli O157:H7, and in particular the percentage of animals shedding enumerable levels of the pathogen did not change, indicating that there was not a change in colonization. As has been reported previously and indicated again in this study, the use of WDGS in the diet may increase E. coli O157:H7 shedding. In contrast, the addition of SBM to cattle diets, to increase the dietary crude protein, appeared to reduce E. coli O157:H7 shedding, but this potential dietary intervention needs to be confirmed with additional research.

Effects of zilpaterol hydrochloride on methane production, total body oxygen consumption, and blood metabolites in finishing beef steers.

An indirect calorimetry experiment was conducted to determine the effects of feeding zilpaterol hydrochloride (ZH) for 20 d on total body oxygen consumption, respiratory quotient, methane production, and blood metabolites in finishing beef steers. Sixteen Angus steers (initial BW = 555 ± 12.7 kg) were individually fed at ad libitum intake and used in a completely randomized design. The model included the fixed effects of dietary treatment, day, and treatment × day. Dry matter intake did not differ between the treatments ( = 0.89), but was greater on d 0 than any other day ( < 0.01). Oxygen consumption was not different between treatments ( = 0.79), but was different across day ( < 0.01) on d 7, 14, 21, and 28. Respiratory quotient was less for cattle fed ZH than control ( < 0.01), and also different across day ( < 0.01), being greater on d 7, 21, and 28 than d 3 or 21. Methane production (L/kg of DMI) was greater for steers fed the control vs. the ZH diet ( < 0.01), and it also differed by day ( < 0.01), being greater on d 21 and 28 than d 0, 3, 7, and 14. Nonesterified fatty acids were not different across treatments ( = 0.82), and there was no effect of treatment on ß-hydroxybutyrate concentration ( = 0.45). Whole blood glucose concentrations were not affected by feeding ZH in this experiment ( = 0.76); however, lactate concentrations were reduced by feeding ZH ( = 0.03). Additionally, there was no treatment effect on ɑ-amino-N, blood glutamate, or glutamine ( ≥ 0.16). Plasma NH was not affected by ZH ( = 0.07), but plasma urea nitrogen was reduced by ZH ( < 0.01). Urinary creatinine was increased by steers receiving ZH ( = 0.01), and urine 3-methylhistidine (3-MH) concentrations were normalized to creatinine, the 3-MH:creatinine ratio decreased from d 0 to d 3 in steers fed ZH, and remained less than control steers until d 28. These data provide insight into how ß-agonists alter nutrient partitioning and improve the efficiency of tissue accretion, mainly through decreased muscle protein turnover and altering the catabolic fuel for peripheral tissues.

Effects of trimethylsilane plasma coating on the hydrophobicity of denture base resin and adhesion of Candida albicans on resin surfaces.

STATEMENT OF PROBLEM: Candida-associated denture stomatitis is the most common oral mucosal lesion among denture wearers. Trimethylsilane (TMS) plasma coating may inhibit the growth of Candida albicans on denture surfaces. PURPOSE: The purpose of this in vitro study was to investigate whether TMS plasma coatings can effectively reduce C albicans adhesion on denture base acrylic resin surfaces. MATERIAL AND METHODS: Sixty denture base acrylic resin disks with smooth and rough surfaces were prepared and were either left untreated (control group) or coated with TMS monomer (experimental group) by using plasma. Contact angles were measured immediately after TMS plasma coating. The morphology of C albicans adhesion was observed with scanning electron microscopy (SEM). Energy-dispersive spectroscopy (EDS) was used to characterize the elemental composition of the specimen surface. An adhesion test was performed by incubating the resin disk specimens in C albicans suspensions (1×107 cells/mL) at 37°C for 24 hours and further measuring the optical density of the C albicans by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay test. One-way ANOVA and 2-way ANOVA were followed by a post hoc test analysis (α=.05). RESULTS: The group with TMS coating exhibited a more hydrophobic surface than the control group. EDS analysis revealed successful TMS plasma coating. The difference in the mean contact angles between the uncoated group and the TMS-coated group was statistically significant (P<.05), 79.0 ±2.9 degrees versus 105.7 ±1.5 degrees for the smooth surface and 90.2 ±7.6 degrees versus 131.5 ±2.1 degrees for the rough surface. In SEM analysis, the C albicans biofilm was found to grow more on the surface of the denture base resin without the TMS coating than on the surfaces of the experimental group. In the adhesion test, the amount of C albicans adhering to the surface of denture base resin with the TMS coating was significantly less than that on the surfaces without TMS coating (P<.05). CONCLUSIONS: TMS coating significantly reduced the adhesion of C albicans to the denture base resin and may reduce denture stomatitis.

Fabrication yields of serially harvested calf-fed Holstein steers fed zilpaterol hydrochloride.

Holstein steers ( = 110) were fed zilpaterol hydrochloride (ZH) for 0 or 20 d before slaughter during a 280-d serial harvest study. Cattle were harvested every 28 d beginning at 254 d on feed (DOF) and concluding at 534 DOF. After slaughter, carcasses were chilled for 48 h and then fabricated into boneless closely trimmed or denuded subprimals, lean trim, trimmable fat, and bone. Inclusion of ZH increased cold side weight (CSW) by 10.3 kg ( < 0.01; 212.7 vs. 202.4 kg [SEM 1.96]) and saleable yield by 10.4 kg ( < 0.01; 131.9 vs. 121.5 kg [SEM 1.16]) in calf-fed Holstein steer carcasses. Additionally, saleable yield as a percentage of CSW increased ( ≤ 0.01) by 2.19% (62.64 vs. 60.45% [SEM 0.22]) for cattle supplemented with ZH. Subprimal weights were heavier ( ≤ 0.05) from cattle that received ZH except for the bottom sirloin ball tip, back ribs, and outside skirt regardless of slaughter endpoint. Yield of top round, bottom round, and knuckle was increased ( ≤ 0.01) following ZH supplementation by 0.37, 0.24, and 0.18%, respectively. Yield of the top sirloin butt, strip loin, and tenderloin was increased ( ≤ 0.01) concurrent with ZH supplementation by 0.18, 0.11, and 0.09%, respectively. Regarding the rib primal, the rib eye roll tended ( = 0.08) to had increased yield (2.80 vs. 2.72% [SEM 0.03]) with ZH supplementation; both back ribs and blade meat exhibited increased ( ≤ 0.04) yields of 0.04%. Relative to the chuck primal, increased ( ≤ 0.03) yields of shoulder clod, pectoral meat, and mock tender were observed (0.13, 0.07, and 0.04%, respectively). Yield changes for subprimal brisket, plate, and flank were limited to increased ( < 0.01) proportion of flank steak and elephant ear (cutaneous trunci), 0.07 and 0.04%, respectively. Feeding duration notably altered ( ≤ 0.01) weights and percentages of all subprimals except the brisket. Saleable yield increased ( ≤ 0.01) by 0.192 kg/d with additional DOF. Moreover, trimmable fat and bone increased ( ≤ 0.01) by 0.146 and 0.050 kg/d, respectively. These data illustrate improved saleable meat yields for calf-fed Holstein steers supplemented with ZH and provide the beef industry knowledge of fabrication yield changes throughout a wide range of harvest endpoints.

Acute exposure of primary rat soleus muscle to zilpaterol HCl (ß2 adrenergic agonist), TNFα, or IL-6 in culture increases glucose oxidation rates independent of the impact on insulin signaling or glucose uptake.

Recent studies show that adrenergic agonists and inflammatory cytokines can stimulate skeletal muscle glucose uptake, but it is unclear if glucose oxidation is similarly increased. Thus, the objective of this study was to determine the effects of ractopamine HCl (ß1 agonist), zilpaterol HCl (ß2 agonist), TNFα, and IL-6 on glucose uptake and oxidation rates in unstimulated and insulin-stimulated soleus muscle strips from adult Sprague-Dawley rats. Effects on phosphorylation of Akt (phospho-Akt), p38 MAPK (phospho-p38), and p44/42 MAPK (phospho-p44/42) was also determined. Incubation with insulin increased (P<0.05) glucose uptake by ∼47%, glucose oxidation by ∼32%, and phospho-Akt by ∼238%. Insulin also increased (P<0.05) phospho-p38, but only after 2h in incubation. Muscle incubated with ß2 agonist alone exhibited ∼20% less (P<0.05) glucose uptake but ∼32% greater (P<0.05) glucose oxidation than unstimulated muscle. Moreover, co-incubation with insulin+ß2 agonist increased (P<0.05) glucose oxidation and phospho-Akt compared to insulin alone. Conversely, ß1 agonist did not appear to affect basal or insulin-stimulated glucose metabolism, and neither ß agonist affected phospho-p44/42. TNFα and IL-6 increased (P<0.05) glucose oxidation by ∼23% and ∼33%, respectively, in the absence of insulin. This coincided with increased (P<0.05) phospho-p38 and phospho-p44/42 but not phospho-Akt. Furthermore, co-incubation of muscle with insulin+either cytokine yielded glucose oxidation rates that were similar to insulin alone, despite lower (P<0.05) phospho-Akt. Importantly, cytokine-mediated increases in glucose oxidation rates were not concomitant with greater glucose uptake. These results show that acute ß2 adrenergic stimulation, but not ß1 stimulation, directly increases fractional glucose oxidation in the absence of insulin and synergistically increases glucose oxidation when combined with insulin. The cytokines, TNFα and IL-6, likewise directly increased glucose oxidation in the absence of insulin, but were not additive in combination with insulin and in fact appeared to disrupt Akt-mediated insulin signaling. Rather, cytokines appear to be acting through MAPKs to elicit effects on glucose oxidation. Regardless, stimulation of glucose oxidation by these key stress factors did not rely upon greater glucose uptake, which may promote metabolic efficiency during acute stress by increasing fractional glucose oxidation without increasing total glucose consumption by muscle.

Interaction between supplemental zinc oxide and zilpaterol hydrochloride on growth performance, carcass traits, and blood metabolites in feedlot steers.

Interactive effects of supplemental Zn and zilpaterol hydrochloride (ZH) were evaluated in feedlot steers ( = 40; 652 kg ± 14 initial BW) to determine their impact on feedlot performance, blood constituents, and carcass traits. The study was conducted as a randomized complete block design with a 2 × 2 factorial treatment arrangement. Steers were blocked by BW and randomly assigned to treatments. Factors consisted of supplemental Zn (60 or 300 mg/kg diet DM) and ZH (0 or 8.33 mg/kg) in the diets. For diets supplemented with 300 mg Zn/kg DM, 60 mg Zn/kg was supplemented as zinc sulfate and 240 mg Zn/kg was supplemented as zinc oxide, and the diet was fed for 24 d. Zilpaterol hydrochloride was fed for 21 d followed by a 3-d withdrawal. Cattle were housed in partially covered individual feeding pens equipped with automatic waterers and fence-line feed bunks and were fed once daily for ad libitum intake. Plasma samples were collected on d 0 and 21 to assess changes in Zn, plasma urea nitrogen (PUN), glucose, and lactate concentrations, and serum samples were collected on d 21 to assess IGF-1 concentration. On d 25, cattle were weighed and transported 450 km to a commercial abattoir for harvest; HCW and incidence of liver abscesses were recorded. Carcass data were collected after 36 h of refrigeration. Data were analyzed as a mixed model with Zn, ZH, and Zn × ZH as fixed effects; block as a random effect; and steer as the experimental unit. No interaction or effects of Zn or ZH were observed for IGF-1 concentration, plasma glucose, or lactate concentrations ( ≥ 0.25). No interaction between Zn and ZH was observed for PUN concentration, but PUN decreased with ZH ( < 0.01). There were no effects of ZH or Zn on ADG, DMI, final BW, feed efficiency, HCW, back fat, KPH, quality grade, or incidence of liver abscesses ( > 0.05). Zinc supplementation tended ( = 0.08) to improve the proportion of carcasses grading USDA Choice. Feeding ZH decreased yield grade ( = 0.05) and tended to increase LM area ( = 0.07). In conclusion, increasing dietary concentrations of Zn does not impact response to ZH, but feeding ZH altered circulating concentrations of PUN.

The effects of animal age, feeding regime and a dietary beta-agonist on tenderness of three beef muscles.

BACKGROUND: Animal age as determined by number of permanent incisors (p. i.) is used in classification of beef carcasses to describe expected meat tenderness. However, animals differing in age are reared under different production systems (pasture or feedlot). In addition to age, other factors associated with particular production systems may also influence the palatability of meat. Therefore, the effects of age combined with feeding regime and the supplementation of a beta-agonist (zilpaterol) on the tenderness of M. longissimus lumborum (LL), M. semitendinosus (ST) and M. biceps femoris (BF) muscles were investigated. RESULTS: Tenderness of LL cuts was least affected by age but zilpaterol significantly decreased tenderness and ageing potential. Tenderness of high-collagen cuts (BF and ST) was negatively affected by age due to reduced collagen solubility. The effect of zilpaterol on these cuts was less significant and BF and ST cuts of the grain-fed A-age animals (0 p. i.) supplemented with zilpaterol (AZ) were more tender than the same cuts of grass-fed animals with 1-2 p. i. (AB-age) and grass-fed animals with 3-6 p. i. (B-age) according to Warner-Bratzler shear force (WBSF) and sensory analysis for tenderness. CONCLUSION: This study indicates that beta-agonists may influence variation in tenderness within an age class more than age or feeding regime. © 2016 Society of Chemical Industry.

The effect of zilpaterol hydrochloride supplementation on energy metabolism and nitrogen and carbon retention of steers fed at maintenance and fasting intake levels.

An indirect calorimetry trial examined energy metabolism, apparent nutrient digestibility, C retention (CR), and N retention (NR) of cattle supplemented with zilpaterol hydrochloride (ZH). Beef steers ( = 20; 463 ± 14 kg) blocked ( = 5) by weight and source were individually fed and adapted to maintenance energy intake for 21 d before allotment to ZH (90 mg/steer∙d) or no ß-adrenergic agonist treatment (control [CONT]) for 20 d (455 ± 14 kg at the start of treatment). Respiration chambers = 4 were used to quantify heat production (HP) during maintenance (d 12 to 16 of the ZH period) and fasting heat production (FHP; d 19 to 20 of ZH period; total 4 d of fast). Steers were harvested after a 6-d ZH withdrawal and carcasses were graded 24 h after harvest. Control cattle lost more BW ( < 0.01; 9 kg for CONT and 2 kg for ZH-treated) during maintenance whereas the BW loss of ZH-treated steers was greater ( < 0.01; 9 kg for ZH-treated and vs. 4 kg, for CONT) during FHP; no differences ( ≥ 0.76) were detected for G:F, ADG, and end BW. No differences in DMI, apparent nutrient digestibility, O consumption, or CH production ( ≥ 0.12) were detected; however, ZH-treated cattle had greater CO production during maintenance ( = 0.04; 23.6 L/kgBW for ZH-treated and 22.4 L/kg BW for CONT). Digestible energy and ME did not differ ( ≥ 0.19); however, urinary energy was greater ( = 0.05; 0.091 Mcal for CONT and 0.074 Mcal for ZH-treated) in CONT cattle. Steers treated with ZH tended to have greater HP ( = 0.09; 12.44 Mcal for ZH-treated and 11.69 Mcal for CONT), but the effect was reduced on a BW basis ( = 0.12; 0.126 Mcal/kg BW0.75 for ZH-treated and 0.120 Mcal/kg BW0.75 for CONT vs. 0.120 Mcal/kg BW). No treatment difference in FHP was observed ( ≥ 0.32) although CO production (L/steer) increased with ZH treatment ( = 0.04; 1,423 L/steer for ZH-treated and 1,338 L/steer for CONT). Control cattle excreted more ( = 0.05) N in urine (39.8 g/d for CONT and 32.4 g/d for ZH-treated); therefore, NR ( = 0.07; 22.14 g/d for ZH-treated and 14.12 g/d for CONT steers) tended to be greater for ZH-fed steers. Steers treated with ZH lost more C via CO ( = 0.04; 1,036.9 g/d for ZH-treated and 974.3 g/d for CONT) although total CR did not differ ( ≥ 0.23). Empty BW, HCW, and harvest yields (g/kg empty BW) were not different ( ≥ 0.13), whereas ZH increased dressed yield ( = 0.02; 62.12 % for ZH-treated and 60.65% for CONT) and LM area ( = 0.02; 77.81 cm for ZH-treated and vs. 70.90 cm for CONT). Separable carcass lean and actual skeletal muscle protein (SMP) were increased with ZH ( ≤ 0.04; 201.6 and 41.2 kg, respectively for ZH-treated and 196.0 and 38.4 kg, respectively for CONT). Results from this trial indicate that ZH treatment increased ( = 0.03) SMP and tended ( ≥ 0.07) to increase NR and modify HP during maintenance by increasing CO production.

Byproduct yields of serially harvested calf-fed Holstein steers fed zilpaterol hydrochloride.

A 2 × 11 factorial treatment structure was applied in a completely randomized experimental design to investigate differences in noncarcass tissue among serially harvested Holstein steers. Steers ( = 110) were randomly assigned to 1 of 2 dietary treatments: a ration supplemented with zilpaterol hydrochloride (ZH) fed at a rate of 8.3 mg/kg DM for 20 d followed by a 3-d withdrawal or a control ration with no ZH included in the diet. Within treatment, steers were assigned to harvest groups of 254, 282, 310, 338, 366, 394, 422, 450, 478, 506, or 534 d on feed (DOF) prior to initiation of the trial. Cattle fed ZH realized an empty BW (EBW) increase ( ≤ 0.03) of 2.8% (644.2 vs. 626.4 kg [SEM 5.4]) and a HCW increase of 5.0% (429.1 vs. 408.4 kg [SEM 4.0]) with a concomitant 12% reduction (45.1 vs. 51.2 kg [SEM 3.1]) in gastrointestinal contents and 2.1 percentage unit increase in dressed carcass yield (62.1 vs. 60.0% [SEM 0.01]). Additionally, ZH supplementation decreased (P ≤ 0.03) the absolute weight of the liver and kidneys by 0.3 and 0.1 kg, respectively. When noncarcass components were expressed on an empty body basis (g/kg EBW), reductions ( ≤ 0.01) in the limbs (18.8 vs. 19.5 g/kg EBW [SEM 0.1]), hide (81.1 vs. 78.1 g/kg EBW [SEM 0.7]), liver (14.2 vs. 13.2 g/kg EBW [SEM 0.2]), kidneys (2.6 vs. 2.3 g/kg EBW [SEM 0.04]), small and large intestines (74.9 vs. 69.6 g/kg EBW [SEM 1.2]), and gastrointestinal tract (119.8 vs. 113.4 g/kg EBW [SEM 1.3]) were observed with ZH supplementation. Additionally, there was a tendency ( = 0.07) for the proportion of total offal to be reduced (253.2 vs. 247.4 g/kg EBW [SEM 2.5]) with ZH supplementation. Empty BW and HCW linearly increased ( < 0.01) by 1.16 and 0.758 kg/d ( < 0.01), respectively, with additional DOF. The weight of the liver and intestines linearly increased ( < 0.01) by 0.007 and 0.133 kg/d ( < 0.01), respectively, with additional DOF. These data indicate the magnitude of change in noncarcass tissues that can be expected when calf-fed Holstein steers are supplemented with ZH.

Effect of ractopamine hydrochloride and zilpaterol hydrochloride on cardiac electrophysiologic and hematologic variables in finishing steers.

OBJECTIVE To investigate the effects of dietary supplementation with the ß-adrenoceptor agonists ractopamine hydrochloride and zilpaterol hydrochloride on ECG and clinicopathologic variables of finishing beef steers. DESIGN Randomized controlled trial. ANIMALS 30 Angus steers. PROCEDURES Steers were grouped by body weight and randomly assigned to receive 1 of 3 diets for 23 days: a diet containing no additive (control diet) or a diet containing ractopamine hydrochloride (300 mg/steer/d) or zilpaterol hydrochloride (8.3 mg/kg [3.8 mg/lb] of feed on a dry-matter basis), beginning on day 0. Steers were instrumented with an ambulatory ECG monitor on days -2, 6, 13, and 23, and continuous recordings were obtained for 72, 24, 24, and 96 hours, respectively. At the time of instrumentation, blood samples were obtained for CBC and serum biochemical and blood lactate analysis. Electrocardiographic recordings were evaluated for mean heart rate and arrhythmia rates. RESULTS Steers fed zilpaterol or ractopamine had greater mean heart rates than those fed the control diet. Mean heart rates were within reference limits for all steers, with the exception of those in the ractopamine group on day 14, in which mean heart rate was high. No differences in arrhythmia rates were identified among the groups, nor were any differences identified when arrhythmias were classified as single, paired, or multiple (> 2) beats. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that dietary supplementation of cattle with ractopamine or zilpaterol at FDA-approved doses had no effect on arrhythmia rates but caused an increase in heart rate that remained within reference limits.

The metabolic, stress axis, and hematology response of zilpaterol hydrochloride supplemented beef heifers when exposed to a dual corticotropin-releasing hormone and vasopressin challenge.

The objective of this study was to determine the metabolic, stress, and hematology response of beef heifers supplemented with zilpaterol hydrochloride (ZH) when exposed to an endocrine stress challenge. Heifers ( = 20; 556 ± 7 kg BW) were randomized into 2 treatment groups: 1) control (CON), no ZH supplementation, and 2) zilpaterol (ZIL), supplemented with ZH at 8.33 mg/kg (DM basis). The ZIL group was supplemented ZH for 20 d, with a 3-d withdrawal period. On d 24, heifers received an intravenous bolus of corticotropin-releasing hormone (CRH; 0.3 µg/kg BW) and arginine vasopressin (VP; 1.0 µg/kg BW) to activate the stress axis. Blood samples were collected at 30-min intervals for serum and 60-min intervals for plasma and whole blood, from -2 to 8 h relative to the challenge at 0 h (1000 h). Samples were analyzed for glucose, insulin, NEFA, blood urea nitrogen (BUN), cortisol, epinephrine, norepinephrine, and complete blood cell counts. Following the challenge, cattle were harvested over a 3-d period. Liver, LM, and biceps femoris (BF) samples were collected and analyzed for glucose, lactate, and glycolytic potential (GP). There was a treatment ( ≤ 0.001) effect for vaginal temperature (VT), with ZIL having a 0.1°C decrease in VT when compared with CON. A treatment × time effect ( = 0.002) was observed for NEFA. A treatment effect was observed for BUN; ZIL had decreased BUN concentrations compared with CON ( < 0.001) prior to the challenge; however, no treatment × time effect was observed. There was also a treatment effect for cortisol ( ≤ 0.01) and epinephrine ( = 0.003); ZIL had decreased cortisol and epinephrine during the CRH/VP challenge when compared with CON. There was a time effect for total white blood cells, lymphocytes, and monocytes; each variable increased ( ≤ 0.01) 2 h postchallenge. Additionally, neutrophil counts decreased ( ≤ 0.01) in response to CRH/VP challenge in both treatment groups. Glucose concentrations within the LM were greater ( = 0.03) in CON when compared with ZIL. Lactate concentrations and GP within the BF were greater in CON ( = 0.05) when compared with ZIL. These data suggest there are some variations observed between treatments in terms of response to the CRH/VP challenge; however, in the environmental conditions of this trial, none of the variations observed suggest that the supplementation of ZH detrimentally alters the ability of cattle to effectively respond to stressful stimuli.

The effects of zilpaterol hydrochloride and shade on blood metabolites of finishing beef steers.

The effects of feeding zilpaterol hydrochloride (ZH) and shade were evaluated on blood metabolites in finishing beef steers ( = 480). Cattle were fed 0 or 8.33 mg/kg of diet DM ZH for 21 d with a 3- or 4-d withdrawal before harvest and were housed in open or shaded pens. Blood samples were collected the day before ZH was fed and on the day the cattle were shipped to the commercial abattoir. Lactate concentration was not different between cattle fed ZH in open or shaded pens ( = 0.12). Nonetheless, a tendency for a diet × time interaction was detected for lactate concentration ( = 0.09), in which it was greater in cattle fed the control diet in open pens before being fed ZH. Cortisol concentration was less before and after ZH was fed ( = 0.01). Glucose was greater for cattle fed the control diet than cattle fed ZH for 21 d ( = 0.03). Cattle fed in open vs. shaded pens did not differ in glucose concentration ( = 0.12), whereas glucose concentrations were greater before ZH was fed than after ( = 0.02). In contrast, plasma urea nitrogen (PUN) concentration was not different in response to diet ( = 0.24), housing type ( = 0.65), or before vs. after being fed ZH ( = 0.60). Lactate concentrations were not different across diet or shade treatments before ZH was fed, whereas after ZH, lactate concentrations were greater in control cattle than cattle fed ZH. Additionally, cortisol was less after feeding ZH. Glucose was greater before than after feeding ZH.