Preclinical validation of a potent γ-secretase modulator for Alzheimer's disease prevention.

A potent γ-secretase modulator (GSM) has been developed to circumvent problems associated with γ-secretase inhibitors (GSIs) and to potentially enable use in primary prevention of early-onset familial Alzheimer's disease (EOFAD). Unlike GSIs, GSMs do not inhibit γ-secretase activity but rather allosterically modulate γ-secretase, reducing the net production of Aß42 and to a lesser extent Aß40, while concomitantly augmenting production of Aß38 and Aß37. This GSM demonstrated robust time- and dose-dependent efficacy in acute, subchronic, and chronic studies across multiple species, including primary and secondary prevention studies in a transgenic mouse model. The GSM displayed a >40-fold safety margin in rats based on a comparison of the systemic exposure (AUC) at the no observed adverse effect level (NOAEL) to the 50% effective AUC or AUCeffective, the systemic exposure required for reducing levels of Aß42 in rat brain by 50%.

Effects of zinc propionate supplementation on growth performance, skeletal muscle fiber, and receptor characteristics in beef steers.

A randomized complete block design experiment with 32 yearling crossbred steers (average body weight [BW] = 442 ± 17.0 kg) fed a steam-flaked corn-based diet was used to evaluate the effects of dietary Zn (KemTRACE Zn propionate 27; Kemin Industries, Inc., Des Moines, IA) supplementation on live growth performance, skeletal muscle fiber, and beta-adrenergic receptor (ß-AR) characteristics during the finishing phase. Steers were blocked by BW (n = 4 blocks; 8 steers/block), assigned to pens (n = 4 steers/pen), and randomly assigned to the following treatments: control (CON; 0.0 g/[head (hd) · d] of additional Zn) or additional dietary Zn (ZnP; 1.0 g/[hd · d] additional Zn). The basal diet contained Zn (60 ppm dry matter basis) from ZnSO4; additional Zn was top-dressed at feeding. Ractopamine hydrochloride (RH; Optaflexx: Elanco Animal Health, Greenfield, IN) was included at 300 mg/(hd · d) for the final 28 d of the 111-d feeding period. Longissimus muscle biopsy samples, BW, and blood were obtained on days 0, 42, 79, and 107. Final BW was collected prior to shipping on day 111. Biopsy samples were used for immunohistochemical (IHC), mRNA, and protein analysis. Serum urea nitrogen (SUN) and nonesterified fatty acid (NEFA) concentrations were measured. Steers fed ZnP had a greater average daily gain (P = 0.02) and gain to feed ratio (G:F; P = 0.03) during the RH feeding period compared with CON. There were no differences (P > 0.05) in other growth performance variables, carcass traits, mRNA abundance, or relative protein concentration for fiber type and ß-AR. Fiber types I and IIA had no differences in the cross-sectional area; however, the IIX area was greater for CON (P < 0.04) compared with ZnP and increased (P < 0.02) over time. There were no differences between treatments for the ß1-AR density (P > 0.05) in skeletal muscle tissue throughout the study. A treatment × day interaction was observed in ß2-AR density (P = 0.02) and ß3-AR density (P = 0.02) during the RH feeding period, where the abundance of the receptors increased with ZnP but did not change in CON. Compared with CON, ZnP had greater (P < 0.01) mean NEFA concentrations. Mean SUN concentrations did increase by day (P < 0.01). Additional dietary Zn, supplied as Zn propionate, upregulates ß2-AR and ß3-AR and improves growth performance in feedlot steers during the RH feeding period, likely through a shift of resource utilization from lipogenesis to muscle maintenance and hypertrophy.

Heat stress-induced deficits in growth, metabolic efficiency, and cardiovascular function coincided with chronic systemic inflammation and hypercatecholaminemia in ractopamine-supplemented feedlot lambs.

Heat stress hinders growth and well-being in livestock, an effect that is perhaps exacerbated by the ß1 agonist ractopamine. Heat stress deficits are mediated in part by reduced feed intake, but other mechanisms involved are less understood. Our objective was to determine the direct impact of heat stress on growth and well-being in ractopamine-supplemented feedlot lambs. Commercial wethers were fed under heat stress (40 °C) for 30 d, and controls (18 °C) were pair-fed. In a 2 × 2 factorial, lambs were also given a daily gavage of 0 or 60 mg ractopamine. Growth, metabolic, cardiovascular, and stress indicators were assessed throughout the study. At necropsy, 9th to 12th rib sections (four-rib), internal organs, and feet were assessed, and sartorius muscles were collected for ex vivo glucose metabolic studies. Heat stress increased (P < 0.05) rectal temperatures and respiration rates throughout the study and reduced (P < 0.05) weight gain and feed efficiency over the first week, ultrasonic loin-eye area and loin depth near the end of the study, and four-rib weight at necropsy. Fat content of the four-rib and loin were also reduced (P < 0.05) by heat stress. Ractopamine increased (P < 0.05) loin weight and fat content and partially moderated the impact of heat stress on rectal temperature and four-rib weight. Heat stress reduced (P < 0.05) spleen weight, increased (P < 0.05) adrenal and lung weights, and was associated with hoof wall overgrowth but not organ lesions. Ractopamine did not affect any measured indicators of well-being. Heat stress reduced (P < 0.05) blood urea nitrogen and increased (P < 0.05) circulating monocytes, granulocytes, and total white blood cells as well as epinephrine, TNFα, cholesterol, and triglycerides. Cortisol and insulin were not affected. Heat stress reduced (P < 0.05) blood pressure and heart rates in all lambs and increased (P < 0.05) left ventricular wall thickness in unsupplemented but not ractopamine-supplemented lambs. No cardiac arrhythmias were observed. Muscle glucose uptake did not differ among groups, but insulin-stimulated glucose oxidation was reduced (P < 0.05) in muscle from heat-stressed lambs. These findings demonstrate that heat stress impairs growth, metabolism, and well-being even when the impact of feed intake is eliminated by pair-feeding and that systemic inflammation and hypercatecholaminemia likely contribute to these deficits. Moreover, ractopamine improved muscle growth indicators without worsening the effects of heat stress.

Dietary ractopamine supplementation of pregnant sows: what are the impacts on the neonate?

The use of additives such as ractopamine (Rac) in pregnant sows during early-mid pregnancy is an alternative to increase foetal and progeny growth and development. However, Rac supplementation in finishing pigs can lead to behavioural and physiological changes similar to the typical stress responses. The objective of this study was to evaluate the effects of dietary supplementation with Rac in pregnant sows from day 25 to 50 of gestation (pre-hyperplastic stage) on piglet's vitality, blood parameters, number, diameter and perimeter of muscle fibres in semitendinosus muscle and developmental characteristics of piglets at birth to weaning. Forty-one hybrid sows were divided into three dietary treatments: (1) control diet without Rac (control), (2) addition of 10 mg/kg of Rac (Rac10) and (3) addition of 20 mg/kg of Rac (Rac20). Higher numbers of low-vitality piglets (P<0.05) were observed in Rac-fed sows, regardless of dose, compared with the control group. Very low-density lipoprotein levels were lower in the Rac10 group when compared with the Rac20 group at day 21. Haematocrit was greater, and the mean corpuscular haemoglobin concentration was lower in piglets from Rac-fed sows. No significant statistical differences were detected regarding piglets body weight, average daily gain, blood gasometry, complete blood count and muscle fibre measurements in semitendinosus muscle. The use of Rac in pregnant sows reduced the vitality parameters of piglets but did not improve the performance from birth until weaning and did not negatively influence the haematological parameter and lipid metabolism.

Hypertrophic muscle growth and metabolic efficiency were impaired by chronic heat stress, improved by zilpaterol supplementation, and not affected by ractopamine supplementation in feedlot lambs1.

Feedlot performance is reduced by heat stress and improved by ß adrenergic agonists (ßAA). However, the physiological mechanisms underlying these outcomes are not well characterized, and anecdotal reports suggest that ßAA may confound the effects of heat stress on wellbeing. Thus, we sought to determine how heat stress and ßAA affect growth, metabolic efficiency, and health indicators in lambs on a feedlot diet. Wethers (38.6 ± 1.9 kg) were housed under thermoneutral (controls; n = 25) or heat stress (n = 24) conditions for 21 d. In a 2 × 3 factorial, their diets contained no supplement (unsupplemented), ractopamine (ß1AA), or zilpaterol (ß2AA). Blood was collected on days -3, 3, 9, and 21. On day 22, lambs were harvested and ex vivo skeletal muscle glucose oxidation was determined to gauge metabolic efficiency. Feet and organ tissue damage was assessed by veterinary pathologists. Heat stress reduced (P < 0.05) feed intake by 21%, final bodyweight (BW) by 2.6 kg, and flexor digitorum superficialis (FDS) muscle mass by 5%. ß2AA increased (P < 0.05) FDS mass/BW by 9% and average muscle fiber area by 13% compared with unsupplemented lambs. Blood lymphocytes and monocytes were greater (P < 0.05) in heat-stressed lambs, consistent with systemic inflammation. Plasma insulin was 22% greater (P < 0.05) and glucose/insulin was 16% less (P < 0.05) in heat-stressed lambs than controls. Blood plasma urea nitrogen was increased (P < 0.05) by heat stress on day 3 but reduced (P < 0.05) on days 9 and 21. Plasma lipase and lactate dehydrogenase were reduced (P < 0.05) by heat stress. Glucose oxidation was 17% less (P < 0.05) in muscle from heat-stressed lambs compared with controls and 15% greater (P < 0.05) for ß2AA-supplemented compared with unsupplemented lambs. Environment and supplement interacted (P < 0.05) for rectal temperature, which was increased (P < 0.05) by heat stress on all days but more so (P < 0.05) in ß2AA-supplemented lambs on days 4, 9, and 16. Heat stress increased (P < 0.05) the frequency of hoof wall overgrowth, but ßAA did not produce any pathologies. We conclude that reduced performance in heat-stressed lambs was mediated by reduced feed intake, muscle growth, and metabolic efficiency. ß2AA increased muscle growth and improved metabolic efficiency by increasing muscle glucose oxidation, but no such effects were observed with ractopamine. Finally, ßAA supplementation was not detrimental to health indicators in this study, nor did it worsen the effects of heat stress.

Acute oral toxicity and antioxidant studies of an amine-based diselenide.

BACKGROUND: Organochalcogen compounds have attracted the interest of a multitude of studies for their promising Pharmacological and biological activities. The antioxidant activity and acute toxicity of an organoselenium compound, 1-(2-(2-(2-(1-aminoethyl)phenyl)diselanyl)phenyl)ethanamine (APDP) was determined in mice. METHODS: Mice were randomly divided into four groups, with each group comprising of seven animals. Canola oil (1ml/kg of body weight) was administered to 1st group, while 2nd, 3rd & 4th groups were administered with 10 mg/kg, 30 mg/kg & 350 mg/kg of APDP respectively. APDP was administered by Intragastric gavage as a single oral dose. RESULTS: The APDP oral administration was found to be safe up to 350 mg/kg of body weight and no deaths of animals were recorded. The lethal dose 50 (LD50) for APDP was determined at 72 h and was estimated to be > 350 mg/kg. After acute treatment, all mice were sacrificed by decapitation to determine the antioxidant enzymes and lipid peroxidation values for the treated mice liver. No fluctuation in lipid peroxidation, vitamin C and non protein thiol (NPSH) levels was observed due to the administration of APDP. hepatic α-ALA-D activity, catalase (CAT), superoxide dismutase (SOD) and the biochemical parameters were evaluated. Experimental observation demonstrated that APDP protected Fe(II) induced thiobarbituric acid reactive substances (TBARS) production in liver homogenate significantly (p < 0.05). The administration of APDP (an amine-based diselenide) both in vitro and in vivo clearly demonstrated that this potential compound has no acute toxicity towards mice among all the tested parameter. CONCLUSION: On the basis of experimental results, it is concluded that APDP is a potential candidate as an antioxidant compound for studying pharmacological properties.

The influence of supplemental zinc and ractopamine hydrochloride on trace mineral and nitrogen retention of beef steers.

The study objective was to determine whether N retention was improved with supplemental Zn above NRC concentrations with or without ractopamine hydrochloride inclusion. Angus crossbred steers (n = 32, 485 ± 26 kg BW) with Genemax gain scores of 4 or 5 were utilized in a 2 × 2 factorial arrangement (8 steers/treatment). Steers were blocked by BW to a finishing diet with 1 of 2 mineral supplementation strategies (ZNTRT), no supplemental Zn (analyzed 32 mg Zn/kg DM; CON) or supranutritional Zn (CON + 60 ppm ZnSO4 + 60 ppm Zn-amino acid complex; analyzed 145 mg Zn/kg DM; SUPZN), fed 56 days in pens equipped with GrowSafe bunks and assigned to ß-agonist (BA) supplementation strategies of 0 (NON) or 300 mg steer-1 d-1 ractopamine hydrochloride (RAC) fed the last 30 d before harvest. Initial 56-d ADG was not affected by ZNTRT (P = 0.66), but DMI was greater in CON vs. SUPZN (P < 0.01). On day 56 (day 1 of BA supplementation), steers (4 groups; 8 steers/group; 2 steers/treatment) were moved to metabolism crates and adapted for 10 d, followed by 5 d of total fecal and urine collection. Total retention of Zn, Mn, Fe, Cu, and N were calculated. Data were analyzed as a 2 × 2 factorial arrangement, with group as a fixed effect and the 3-way interaction of ZNTRT × BA × group as random. No interactions between ZNTRT and BA were noted for any data (P ≥ 0.19). Collection DMI did not differ among treatments (P ≥ 0.23); however, Zn intake was lesser in CON vs. SUPZN (P < 0.01). Fecal and urinary Zn excretion and Zn and Mn retention were lesser in CON vs. SUPZN (P ≤ 0.03); however, Zn retention was not different between NON and RAC (P = 0.43). Retention of Cu and Fe was unaffected by strategies (P ≥ 0.49). Urine output and urine N excretion were greater in NON vs. RAC (P ≤ 0.05). Nitrogen retention (as percent of N intake) was lesser (P = 0.05) in CON (40.0%) vs. SUPZN (44.3%) and lesser (P = 0.02) in NON (39.5%) vs. RAC (44.8%). Zinc and N retention were found to be positively correlated (r = 0.46, P < 0.01). Average daily gain and G:F across the 86-d trial were lesser in NON vs. RAC (P < 0.03). Overall, SUPZN appears to improve N retention, suggesting that increasing dietary Zn may be important for cattle growth beyond that induced by ractopamine hydrochloride.

Interactive effects of supplemental Zn sulfate and ractopamine hydrochloride on growth performance, carcass traits, and plasma urea nitrogen in feedlot heifers.

Interactive effects of supplemental Zn and ractopamine hydrochloride (RH) were evaluated using 156 crossbred heifers (initial BW = 527 kg ± 6.61; gross BW × 0.96) to determine the impact on feedlot performance, plasma urea nitrogen (PUN), and carcass characteristics. The study was conducted as a randomized complete block design with a 2 × 2 factorial arrangement of treatments. Factors consisted of 1) 30 or 100 mg supplemental Zn/kg diet DM (30Zn or 100Zn) as Zn sulfate and 2) 0 or 200 mg RH/heifer daily. Heifers were blocked by BW and assigned randomly within block to treatments for a 43-d trial. Heifers were housed in partially covered feeding pens (3 heifers/pen; 13 pens/treatment) and provided ad libitum access to feed. Ractopamine hydrochloride was fed for 42 d and removed from the diet until cattle were harvested on d 43. Zinc treatments were fed until harvest. Plasma samples were collected on d 0 and 36 to assess changes in plasma Zn and PUN. On d 43, heifers were weighed, then transported to a commercial abattoir where HCW and incidence of liver abscesses were recorded. Carcass data were collected after 32 h of refrigeration. No Zn × RH interactions were observed for plasma Zn or PUN ( ≥ 0.58); however, there was a tendency for a RH × day interaction for PUN ( = 0.08). Supplementing 100Zn resulted in increased plasma Zn ( = 0.02) compared to 30Zn. No RH × Zn interactions were observed for feedlot performance ( ≥ 0.24). Final BW and ADG increased with RH supplementation ( ≤ 0.02), but DMI was not affected ( = 0.63); thus, feed efficiency improved ( < 0.01) when heifers were fed RH. Supplementing 100Zn tended to reduce ADG ( = 0.07) but did not affect other measures of feedlot performance ( ≥ 0.12). Zinc × RH interactions were observed for LM area and yield grade ( ≤ 0.01); LM area decreased and yield grade increased when heifers were supplemented 100Zn with no RH compared to other treatments. A tendency for a Zn × RH interaction was observed for dressed yield ( = 0.08), but no other interactions or effects of Zn were detected for carcass traits ( ≥ 0.11). Supplementing RH increased HCW ( = 0.03) but did not affect other carcass traits ( ≥ 0.13). In conclusion, supplemental Zn had little impact on feedlot performance or PUN concentration but may alter muscle and fat deposition when fed in conjunction with RH.

The Effect of Experimental Supplementation with the Klamath Algae Extract Klamin on Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological condition with onset in childhood. The disorder is characterized by inattention, impulsivity, and/or motor hyperactivity, which often affect the development and social integration of affected subjects. Phenylethylamine (PEA), naturally contained in the Klamath Lake microalgae and concentrated in the Klamin® extract, is an endogenous molecule with a general neuromodulatory activity. It functions as an activator for the neurotransmission of dopamine and other catecholamines, and very low concentrations of PEA may be associated with specific psychological disorders such as ADHD. The aim of our study was to evaluate the efficacy of the Klamin extract in treating a group of subjects diagnosed with ADHD. Thirty subjects, aged 6-15, who had been diagnosed with ADHD according to the DSM-IV TR criteria, were enrolled. The supplement was administered to all the subjects, who reported to an ADHD clinic for routine follow-up visits. Observations were made and data collected over a 6-month period. After 6 months of therapy the subjects appeared to show significant improvements based on assessments of their overall functioning, behavioral aspects related to inattention and hyperactivity-impulsivity, attention functions in both the selective and sustained component and executive functions. The study appears to confirm the initial hypothesis that the Klamin extract may positively affect the expression of ADHD symptoms. Additional larger studies on the effects of Klamin on ADHD are needed to further investigate the potential of this extract in ADHD treatment.

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.

The effects of increasing supplementation of zinc-amino acid complex on growth performance, carcass characteristics, and inflammatory response of beef cattle fed ractopamine hydrochloride.

Forty-two Angus crossbred steers (380 ± 5.3 kg) were enrolled in a finishing study to evaluate the influence of a supplemental Zn amino-acid complex (ZnAA; Availa-Zn) on performance and carcass characteristics of finishing steers in combination with ractopamine hydrochloride (RAC). Steers were stratified by BW into 7 pens of 6 steers each, and individual feed intake was measured. Steers were assigned to 1 of 4 treatments for 86 d (pre-RAC period): a dry-rolled corn-based diet supplemented with 60 mg Zn/kg DM from ZnSO and no supplemental ZnAA (CON; analyzed 88 mg Zn/kg DM; = 6) or CON diet supplemented with 30 (Zn30; = 12), 60 (Zn60; = 12), or 90 (Zn90; = 11) mg Zn/kg DM from ZnAA. Day 86 BW and G:F displayed a quadratic tendency ( = 0.09) with Zn60 steers being greater than the other treatments. Plasma cyclic adenosine monophosphate tended to linearly increase with increasing ZnAA ( = 0.10). On d 88, 6 of 12 steers (one of the 2 pens) receiving supplemental ZnAA was randomly selected to be supplemented with RAC at 300 mg∙steer∙d for the final 28 d of the experiment (RAC period). This created 7 final treatments: CON: no supplemental ZnAA, no RAC ( = 5); Zn30: Zn30, no RAC ( = 5); Zn30R: Zn30 + RAC ( = 6); Zn60: Zn60, no RAC ( = 6); Zn60R: Zn60 + RAC ( = 6); Zn90: Zn90, no RAC ( = 5); and Zn90R: Zn90 + RAC ( = 6). During the RAC period, as supplemental ZnAA increased within RAC-supplemented treatments, there was a linear increase in final BW, ADG, and G:F ( < 0.05). However, there was no effect of supplemental ZnAA on BW, ADG, or G:F during this period in non-RAC fed steers ( ≥ 0.44). Day 111 plasma Cu was increased, plasma Fe decreased, and leukocyte counts and serum interleukin-8 concentrations were greater ( < 0.05) in RAC-fed steers suggesting that RAC may elicit a mild inflammatory response. There was a tendency for increasing Zn supplementation to decrease plasma haptoglobin within RAC-fed steers ( = 0.07), suggesting that Zn may alter the inflammatory response. Overall, Zn60 improved growth performance during the pre-RAC period. Zinc supplemented as ZnAA appears to improve growth in combination with RAC supplementation, suggesting that Zn may enhance or support the biological function of RAC. Additionally, these results indicate that feeding RAC impacts trace mineral status, and potentially causes a non-specific inflammatory response, but further research is required to define this response.

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.

Effects of supplementing zinc or chromium to finishing steers fed ractopamine hydrochloride on growth performance, carcass characteristics, and meat quality.

Objectives were to determine the effects of feeding ractopamine hydrochloride (RAC) with zinc (Zn) and chromium (Cr) on feedlot growth performance, carcass characteristics, and meat quality. Steers ( = 179; initial BW = 533 ± 94 kg) were blocked by BW and allotted to 30 pens, and pens were randomly assigned 1 of 5 treatments: (1) control (CONT), (2) RAC only (RO), (3) RAC + Zn (RZ), (4) RAC + Cr (RC), or (5) RAC + Zn + Cr (RZC). Trace minerals were fed from d 0 to 63 to target 1 g of Zn/steer·d (KemTRACE Zn; Kemin Industries, Inc., Des Moines, IA) and 3 mg Cr/steer·d (KemTRACE Chromium; Kemin Industries, Inc.) for Zn and Cr treatments, respectively. Dry-rolled corn, 0.605 kg/steer, was removed from the diet and 400 mg RAC, per 0.605 kg of ground corn carrier, was top dressed per steer immediately following feed delivery to pens fed RAC. There were no effects ( ≥ 0.45) of trace mineral supplementation on DMI, ADG, or G:F before RAC feeding. There were also no treatment effects ( ≥ 0.46) over all 63 d of the trial on DMI, ADG, or G:F. Despite the lack of differences in live performance, steers fed RO and RC averaged 0.10 kg/d greater ( = 0.10) carcass ADG than steers fed RZC and CONT, while steers fed RZ were intermediate and not different. Steers fed RO had the greatest ( = 0.09) carcass G:F, while steers fed CONT had the least carcass G:F, 0.0875 and 0.0774, respectively. Steers fed RO and RC averaged 5.5 kg heavier ( = 0.09) HCW than steers fed RZC and CONT, while steers fed RZ were intermediate and not different. There were no treatment effects ( ≥ 0.32) on LM area, 12th rib fat, marbling score, KPH, carcass yield, or USDA yield grade and distribution. However, carcasses from steers fed RC had the greatest ( = 0.10) percentage grading USDA Select. There were no treatment effects ( ≥ 0.20) on shear force, intramuscular fat, pH, a*, and b*. Steaks from steers fed RO and RC had 11.4% greater ( = 0.08) cook loss than steaks from steers fed CONT and RZC, whereas steaks from steers fed RZ were intermediate and not different. Also, steaks from steers fed RC had 2.11 units greater ( = 0.03) L* values (i.e., were lighter) than steaks from steers fed RZ; steaks from steers fed CONT, RO, and RZC were intermediate. In feedlot steers, the addition of both Cr and Zn supplementation did not improve growth performance or meat quality when fed in combination with 28 d of RAC supplementation; however, RAC, fed alone or in combination with Cr, did increase HCW.

Ionophore strategy affects growth performance and carcass characteristics in feedlot steers.

One hundred ninety-two steers (BW = 354 ± 23.5 kg) were used in a randomized block design to evaluate the effects of ionophore and ractopamine hydrochloride (RH) supplementation strategies on performance and carcass characteristics. Twelve pens of 4 steers were assigned to each of the following treatments: unsupplemented control (CON), laidlomycin propionate (12.1 mg/kg DM) with or without RH (LPRH and LP, respectively), and monensin sodium (36.4 mg/kg DM) with RH (MSRH). Steers were fed for 151 d, of which respective treatments received RH (Actogain; Zoetis, Florham Park, NJ) at a rate of 300 mg/(animal · d) for the final 32 d. Laidlomycin was removed from the LPRH treatment during this period, as no combination feeding has been approved. Upon harvest, carcass data were collected by trained personnel, and subsequent analysis of the LM was conducted to estimate tenderness using Warner-Bratzler shear force (WBSF). Prior to RH supplementation, both LP and LPRH had greater ADG ( ≤ 0.02) and G:F ( < 0.01) than CON, whereas MSRH was intermediate. During the final 32 d, MSRH improved G:F ( ≤ 0.02) compared to all other treatments and tended to increase ADG over unsupplemented controls ( = 0.05). Cattle receiving LP without RH had significantly greater BW at d 151 than CON ( = 0.02), whereas both RH treatments tended to improve final BW ( ≤ 0.09). Ionophores improved ADG ( ≤ 0.03) and G:F ( < 0.01) for the entire feeding period, and although LP-supplemented cattle had greater DMI for the final 32 d than both RH treatments ( ≤ 0.01), intakes for the 151-d trial were similar among treatments. Carcass weights were greater ( = 0.04) in cattle fed LP with no RH than CON, where cattle yielded an average of 12 kg more HCW. Ractopamine increased LM area in MSRH-supplemented cattle ( = 0.03) and tended to increase LM area for steers receiving LPRH ( = 0.07). Longissimus steaks of MSRH-supplemented cattle had greater WBSF values than CON ( = 0.04) after 7 d of postmortem aging and greater WBSF values than LPRH steaks after 28 d ( = 0.03). All other carcass and WBSF measurements were similar among treatments. The results of this study indicate that LP supplementation without RH may yield a performance similar to and carcass responses associated with the administration of a ß-agonist. These results also suggest that performance and carcass characteristics for cattle fed LP are similar to those of cattle fed monensin throughout the feeding period.

Effects of Added Zinc on Skeletal Muscle Morphometrics and Gene Expression of Finishing Pigs Fed Ractopamine-HCL.

Finishing pigs (n = 320) were used in a 35-day study to determine the effects of ractopamine-HCl (RAC) and supplemental Zinc (Zn) level on loin eye area (LEA) and gene expression. Pens were randomly allotted to the following treatments for the final 35 days on feed: a corn-soybean meal diet (CON), a diet with 10 ppm RAC (RAC+), and RAC diet plus added Zn at 75, 150, or 225 ppm. Sixteen pigs per treatment were randomly selected for collection of serial muscle biopsies and carcass data on day 0, 8, 18, and 32 of the treatment phase. Compared to CON carcasses, RAC+ carcasses had 12.6% larger (P = 0.03) LEA. Carcasses from RAC diets with added Zn had a tendency for increased (quadratic, P < 0.10) LEA compared to the RAC+ carcasses. Compared to RAC+ pigs, relative expression of IGF1 decreased with increasing levels of Zn on day 8 and 18 of treatment, but expression levels were similar on day 32 due to Zn treatments increasing in expression while the RAC+ treatment decreased (Zn quadratic × day quadratic, P = 0.04). A similar trend was detected for the expression of ß1-receptor where expression levels in the RAC+ pigs were greater than Zn supplemented pigs on day 8 and 18 of the experiment, but the magnitude of difference between the treatments was reduced on day 32 due to a decrease in expression by RAC+ pigs and an increase in expression by the Zn pigs (Zn quadratic × day quadratic, P = 0.01). The ability of Zn to prolong the expression of these two genes may be responsible for the tendency of Zn to increase LEA in RAC supplemented pigs.

Effects of ractopamine and arginine dietary supplementation for sows on growth performance and carcass quality of their progenies.

The objective of this study was to evaluate the effects of ractopamine (Rac) and Arg fed to pregnant sows from d 25 to 53 of gestation on fetal muscle development as well as the performance and carcass characteristics of the progeny. One hundred sows were divided into 4 treatments including a control diet, the control plus 1% Arg, the control plus 20 mg/kg Rac, and the control diet supplemented with both additives at the same levels as those used separately. During the farrowing process the data evaluated were the weight of placenta to calculate the placental efficiency and the number of piglets born alive, stillborn, and mummified. To evaluate the fiber number and area, 12 male piglets from each treatment were euthanized to harvest semitendinosus muscle. During the lactation, the preweaning mortality, weaned weights, and number of piglets weaned per litter were evaluated. After weaning, the pig performance was evaluated until the slaughter following the sow treatment. At end of finishing phase, 1 male pig of each treatment replicate was selected to evaluation the carcass and pork quality. All variables measured were analyzed using the MIXED procedure of SAS and least squares means were compared using the Tukey test with P < 0.05. The control diet + supplementation of 1.0% of L-Arg + 20 mg/kg of ractopamine HCl from d 25 to 53 of gestation (Arg+Rac) treatment had a greater number of stillborn piglets (P = 0.014) than the control group. Piglet birth weights from sows fed Rac were 11% greater (P = 0.031) than those of piglets of the control treatment. The semitendinosus muscle fiber diameters of piglets at birth from sows that received Arg, Rac, and Arg+Rac were greater (P < 0.0001) than those of control piglets, and as consequence, the fiber number per square millimeter decreased (P < 0.0001). The final nursery BW of progeny from sows fed Arg and Rac individually were greater (P = 0.010) than those of progeny of the control group. At 110 d of age, in the beginning of the finisher 1 phase, pigs from Arg-fed sows were 1.9 kg heavier (P = 0.010) than pigs from the Arg+Rac-fed sows. The HCW were 2.97 and 1.64 kg heavier (P < 0.0001) for progeny of the Arg and Rac sows, respectively, compared with those of progeny of the control. In conclusion, the trial showed that the use of Rac for gestating sows increased the piglets' weight at birth. The size of muscular fiber was increased in the semitendinosus muscle of piglets originating from sows receiving Rac or Arg. However, the combination of both compounds did not have an additive effect in comparison with the control treatment but increased the stillbirth number.

The interaction of fiber, supplied by distillers dried grains with solubles, with an antimicrobial and a nutrient partitioning agent on nitrogen balance, water utilization, and energy digestibility in finishing pigs.

The objective of this study was to determine if a higher-fiber diet alters the response of finishing pigs to an antimicrobial (tylosin phosphate [TP]) and a nutrient partitioning agent (ractopamine HCl [RAC]) in terms of N and water utilization and energy digestibility. Seventy-two gilts (initial BW = 107.4 ± 4.2 kg) were blocked by weight and allotted to 1 of 8 dietary treatments. Treatments were arranged as a 2 × 2 × 2 factorial: distillers dried grains with solubles (DDGS; 0 vs. 30%), RAC (0 mg of RAC/kg and 0.70% standardized ileal digestible [SID] Lys vs. 5 mg of RAC/kg and 0.95% SID Lys) and TP (0 vs. 44 mg of TP/kg). Pig was the experimental unit, with 9 replications per treatment. Pigs were housed in individual metabolism crates and fed treatment diets for 17 d. Feed was provided twice daily, as much as the pigs could consume within 1 h per meal, and water was provided to the pigs between feeding periods, ad libitum. Fecal and urine collection occurred on d 7 and 8 and on d 15 and 16, for sampling periods 1 and 2, respectively. Pigs fed the DDGS diets had reduced ADG ( < 0.001) and ADFI ( < 0.0001). The apparent total tract digestibility (ATTD) of N and GE were lower for the 30% DDGS diets than the 0% DDGS diets ( < 0.0001). Ractopamine improved ADG ( < 0.0001), G:F ( < 0.0001), and N retention ( < 0.001) and tended to increase daily water intake ( < 0.10). Pigs fed RAC had higher N intake and urinary excretion and lower N retention in Period 2 than in Period 1 ( < 0.05), indicating a decline in the response to RAC over time. Tylosin phosphate did not affect ADFI or G:F but did improve ATTD of N ( < 0.05). There was a tendency for a TP × DDGS interaction ( < 0.10) for ADG, where TP tended to increase ADG in pigs fed 0% DDGS diets ( < 0.10) but not in pigs fed 30% DDGS diets ( > 0.10). Pigs fed DDGS diets had higher N intake ( < 0.01) and higher fecal ( < 0.0001) and urinary ( < 0.01) N excretion with no difference in N retention (g/d). Overall, RAC increased N retention by 33% ( < 0.0001) and the response to RAC was similar in both corn-soybean meal-based and corn-soybean meal-DDGS-based diets. Tylosin phosphate tended to improve growth performance in pigs fed corn-soybean meal-based diets but not in diets containing 30% DDGS; however, this response was not explained by changes in N balance or in energy digestibility.

A comparison of slice characteristics and sensory characteristics of bacon from immunologically castrated barrows with bacon from physically castrated barrows, boars, and gilts.

The objectives were to compare slice characteristics and sensory attributes of bacon from immunologically castrated (IC) barrows with bacon from other sexes using a trained sensory panel. Bacon was obtained for sensory evaluation from 3 experiments. In Exp. 1, trimmed and squared bellies (n=180) of IC barrows, IC barrows fed ractopamine hydrochloride (IC+RAC), physically castrated (PC) barrows, intact males (IM), and gilts were used. Data were analyzed as a general linear mixed model and pen (n=48) served as the experimental unit. Treatment (sex or diet) was a fixed effect in all 3 experiments. In Exp. 2, untrimmed, natural fall bellies (n=96) from IC and PC barrows fed 0 or 30% or a withdrawal distillers dried grains with solubles (DDGS) program when slaughtered at 5 wk after the second dose (25 wk of age) were used. In Exp. 3, untrimmed, natural fall bellies (n=96) from IC and PC barrows fed the same experimental diets as in experiment 2 but slaughtered at 7 wk after the second dose (27 wk of age) were used. Data from Exp. 2 and 3 were analyzed as a 2×3 factorial arrangement in a randomized complete block design and pen was the experimental unit. Bellies from all 3 experiments were processed using the same protocols. In Exp. 1, IM had the greatest (P<0.0001) boar aroma and flavor scores among all treatments. No differences were detected among the other treatment groups for boar aroma or flavor. Intact males had the least (P<0.0001) desirable cured bacon aroma and flavor among all treatments. No differences were detected among the other treatment groups for bacon aroma or flavor. There were no differences in bacon aroma or off-flavor between IC and PC barrows slaughtered at 5 wk after the second dose regardless of DDGS feeding program. Bacon from PC barrows was saltier (P<0.01) than bacon from IC barrows when slaughtered at 5 wk after the second dose. There were no differences in bacon aroma, off-aroma, bacon flavor, or saltiness between IC and PC barrows slaughtered at 7 wk after the second dose regardless of DDGS feeding program. Total slice area of bacon slices from IC barrows slaughtered at 5 wk after the second dose were less (P<0.01) than PC barrows, but the differences diminished (P=0.16) when slaughtered at 7 wk after the second dose. Overall, panelists successfully detected boar odor and flavor in Exp. 1. Immunological castration was as effective as physical castration at eliminating boar aroma and boar flavor in bacon even when feeding differing DDGS feeding programs or when slaughtered at 5 or 7 wk after the second dose.

Retrospective observational study to investigate Sinerga, a multifactorial nutritional product, and bacterial extracts in the prevention of recurrent respiratory infections in children.

In this retrospective observational clinical study, 167 children, aged 3 to 7 years, of both sexes, with a clinical history of recurrent respiratory infections, administered with bacterial extracts of first and second generation or Sinerga a nutritional product containing palmitoylethanolamide, bovine colostrum, phenylethylamine and the new generation of probiotic kluyveromyces FM B0399, were observed. The goal of the study was to compare the supplementation with Sinerga with the supplementation with bacterial extracts, for the effect on the frequency of episodes of respiratory infection that had resulted in a prescription for antibiotics. The study focused retrospectively on the months from March 2013 to November 2012. The results showed a greater reduction in the frequency of respiratory infections with antibiotic therapy in the group of children supplemented with Sinerga than in the group treated with bacterial extracts. In particular, it was observed that 49.3% of the children supplemented with Sinerga, against 5% of those supplemented with extracts, had no infectious episodes requiring the administration of an antibiotic. 100% of subjects supplemented with Sinerga have had no more than two episodes of respiratory infection, while this condition, in the cohort treated with bacterial extracts, was observed in only 51% of cases.

Comparative effects of supplementing beef steers with zilpaterol hydrochloride, ractopamine hydrochloride, or no beta agonist on strip loin composition, raw and cooked color properties, shear force, and consumer assessment of steaks aged for fourteen or twenty-one days postmortem.

Beef steers (n = 1,914) were assigned to 1 of 3 ß-adrenergic agonist (ßAA) supplementation treatments-zilpaterol hydrochloride (ZH; 8.3 mg/kg of DM for 20 d with 3-d withdrawal), ractopamine hydrochloride (RH; 308 mg·head(-1)·d(-1) for 28 d), or no ßAA (CON)-to determine the effects on consumer eating quality. Strip loins (n = 1,101; CON = 400, RH = 355, and ZH = 346) were obtained and fabricated into 2.5-cm-thick steaks for proximate, Warner-Bratzler shear force (WBSF), slice shear force (SSF), and consumer analyses; steaks were aged until 14 or 21 d postmortem. Fat and moisture contents were not affected by ßAA supplementation (P > 0.05), but strip steaks from steers fed ZH had more protein (P < 0.01) than those from steers fed CON or RH, which were similar. An interaction between ßAA and aging was observed (P < 0.01) for WBSF but not SSF. Within steaks aged 14 d, ZH steaks required the most force to shear, RH steaks were intermediate, and CON steaks had the lowest WBSF values; however, RH steaks had a stronger response to aging than CON or ZH steaks, resulting in the lowest WBSF values at 21 d. Slice shear force values were greater (P < 0.01) in steaks from steers fed ZH than in steaks from steers fed CON or RH, which did not differ. Following shear force analyses, steaks within 2 SD of each treatment mean for WBSF were selected randomly for consumer assessment of eating quality. Consumer testing (n = 400; 200/postmortem aging period) was arranged in a 3 × 3 factorial representing 3 quality grades (Select, Low Choice, and Premium Choice) and 3 treatments (ZH, RH, and CON). In steaks aged 14 d, ßAA supplementation affected (P < 0.01) tenderness, flavor, and overall liking and tenderness acceptability, resulting in lower consumer scores for ZH than CON and RH; however, juiciness, flavor, and overall acceptability were similar (P > 0.05). In steaks aged 21 d, feeding ßAA influenced (P < 0.01) only tenderness and juiciness scores. Despite these differences, ßAA did not affect (P > 0.05) acceptability. Quality grade impacted (P < 0.01) all traits and acceptability in steaks aged 14 and 21 d. In 14-d steaks, Premium Choice typically was scored higher than Low Choice or Select; however, consumers rated 21-d Low Choice and Premium Choice similarly-both receiving greater scores than Select. Consumers detected several differences in eating quality at 14 d because of ßAA supplementation. Increasing aging from 14 to 21 d mitigated differences in shear force and tenderness scores because of feeding ZH, so that tenderness and overall acceptability were similar between ZH, RH, and CON.