A Phase 1 Single-Ascending-Dose Trial in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Intravenous PNT001, a Novel Mid-domain Tau Antibody Targeting cis-pT231 Tau.

BACKGROUND: PNT001 is a humanized full-length IgG4 S228P monoclonal antibody that binds the cis conformation of the phosphorylated Thr231-Pro232 motif in human full-length (2N4R) tau (cis-pT231 tau) with high selectivity and affinity. It binds selectively to cis-pT231 tau in human tauopathy brain sections, inhibits aggregation of tau, and has shown efficacy in preclinical models of tauopathy. Good Laboratory Practice six-month toxicology studies in cynomolgous monkeys have shown no test article-related findings. OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of single escalating intravenous doses of PNT001 in healthy volunteers. DESIGN: Phase 1, randomized, double-blind, and placebo-controlled 16-week study. SETTING: Subjects were recruited across three clinical research sites in the United States. PARTICIPANTS: Fifty healthy volunteer subjects enrolled, with 49 receiving the double-blind study drug. INTERVENTION: Six cohorts were administered single escalating doses of PNT001 (33, 100, 300, 900, 2,700, and 4,000 mg). The subjects were randomized 6:2 (PNT001:placebo). MEASUREMENTS: Safety was evaluated by the occurrence of adverse events, electrocardiography, physical examinations, neurological examinations, vital signs, and suicidality. Pharmacokinetics and biomarkers were assessed via serum and cerebrospinal fluid sample analyses. RESULTS: Dose continuation after review of sentinel group data and dose escalation after completion of full cohort data were determined by an external, independent safety board. There were no study pauses or safety concerns identified by the safety board. A total of 49 subjects received the study drugs, with 36 receiving PNT001 and 13 receiving placebo. There were three related non-serious adverse events, each Grade 1, which occurred at the lowest doses and resolved without sequelae. No maximum tolerated dose was identified, and no premature discontinuations, dose reductions, or interruptions due to treatment-related adverse events occurred. One unrelated serious adverse event occurred in a placebo subject with an undisclosed medical condition. No other safety findings were identified. Doses of 900-4,000 mg produced concentrations in the cerebrospinal fluid exceeding the binding affinity constant of PNT001 for cis-pT231 tau (45 ng/mL), indicating that concentrations sufficient for target engagement can be obtained in the cerebrospinal fluid within the tested dose range. The serum pharmacokinetic profile was as expected for a monoclonal antibody. The terminal half-lives ranged from 23.8-33.8 days, and the cerebrospinal fluid exposures were approximately 0.1% of the plasma concentration and dose-proportional. Of the 36 subjects receiving PNT001, one post-baseline positive anti-drug antibody result was observed at Day 112 in a subject who received PNT001 (300 mg). CONCLUSIONS: Single doses of PNT001 were safe and well-tolerated at all dose levels studied, including those doses expected to produce therapeutic benefit. These results support multiple ascending dose trials in patients with neurodegenerative tauopathies for this novel mid-domain tau antibody.

Pharmacological characterization of the first in class clinical candidate PF-05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose-dependent insulin secretion ex vivo.

BACKGROUND AND PURPOSE: Ghrelin increases growth hormone secretion, gastric acid secretion, gastric motility and hunger but decreases glucose-dependent insulin secretion and insulin sensitivity in humans. Antagonizing the ghrelin receptor has potential as a therapeutic approach in the treatment of obesity and type 2 diabetes. Therefore, the aim was to pharmacologically characterize the novel small-molecule antagonist PF-05190457 and assess translational pharmacology ex vivo. EXPERIMENTAL APPROACH: Radioligand binding in filter and scintillation proximity assay formats were used to evaluate affinity, and europium-labelled GTP to assess functional activity. Rat vagal afferent firing and calcium imaging in dispersed islets were used as native tissues underlying food intake and insulin secretion respectively. KEY RESULTS: PF-05190457 was a potent and selective inverse agonist on constitutively active ghrelin receptors and acted as a competitive antagonist of ghrelin action, with a human Kd of 3 nM requiring 4 h to achieve equilibrium. Potency of PF-05190457 was similar across different species. PF-05190457 increased intracellular calcium within dispersed islets and increased vagal afferent firing in a concentration-dependent manner with similar potency but was threefold less potent as compared with the in vitro Ki in recombinant overexpressing cells. The effect of PF-05190457 on rodent islets was comparable with glibenclamide, but glucose-dependent and additive with the insulin secretagogue glucagon-like peptide-1. CONCLUSIONS AND IMPLICATIONS: Together, these data provide the pharmacological in vitro and ex vivo characterization of the first ghrelin receptor inverse agonist, which has advanced into clinical trials to evaluate the therapeutic potential of blocking ghrelin receptors in obesity and type 2 diabetes.

On the thermal elevation of a 60-electrode epiretinal prosthesis for the blind.

In this paper, the thermal elevation in the human body due to the operation of a dual-unit epiretinal prosthesis to restore partial vision to the blind affected by irreversible retinal degeneration is presented. An accurate computational model of a 60-electrode device dissipating 97 mW power, currently under clinical trials is developed and positioned in a 0.25 mm resolution, heterogeneous model of the human head to resemble actual conditions of operation of the prosthesis. A novel simple finite difference scheme combining the explicit and the alternating-direction implicit (ADI) method has been developed and validated with existing methods. Simulation speed improvement up to 11 times was obtained for the the head model considered in this work with very good accuracy. Using this method, solutions of the bioheat equation were obtained for different placements of the implant. Comparison with in-vivo experimental measurements showed good agreement.

Characteristics of lambs fed concentrates or grazed on ryegrass to traditional or heavy slaughter weights. II. Wholesale cuts and tissue accretion.

Targhee x Hampshire lambs (average BW 24 +/- 1 kg) were used to determine the effect of finishing on concentrate or by grazing ryegrass forage on slaughter weights of 52 kg (N) or 77 kg (H) on tissue accretion and lamb wholesale cutout. When fed to similar slaughter weights, the wholesale cuts of concentrate-fed lambs were heavier (P < 0.05) than the same cuts from forage-fed lambs; however, when expressed as a percentage of side weight, carcasses of forage-fed lambs had a higher (P < 0.001) percentage of leg than concentrate-fed lambs. Increasing slaughter weight from 52 to 77 kg resulted in a 1-kg increase in loin weight for lambs finished on concentrate and a 0.60-kg increase for lambs finished on forage (diet x slaughter weight, P < 0.03); however, the increased loin weight for lambs finished on concentrate was due largely to increased fat deposition. For lambs slaughtered at 77 kg, those finished on forage had more lean mass in the leg, loin, rack, and shoulder than those finished on concentrate, but lean mass in these cuts did not differ between diets for lambs slaughtered at 52 kg (diet x slaughter weight, P < 0.01). At the normal slaughter weight (52 kg), concentrate-fed lambs had 50% more dissectible fat than forage-fed lambs, whereas at the heavy slaughter weight, a 79% greater amount of dissectible fat was observed for concentrate- vs. forage-fed lambs (diet x slaughter weight, P < 0.001). Lean and fat accretion rates were higher (P < 0.001) for concentrate-fed lambs than for forage-fed lambs. The lean-to-fat ratio of forage-fed lambs was higher (P < 0.001) than that of concentrate-fed lambs; however, forage finishing decreased accretion rates of all tissues compared with concentrate feeding, and these differences between forage and concentrate feeding were magnified at heavier slaughter weights.

Comparison of characteristics of lambs fed concentrate or grazed on ryegrass to traditional or heavy slaughter weights. I. Production, carcass, and organoleptic characteristics.

The objectives of this study were to determine the effects of finishing lambs on concentrate (C) or by grazing ryegrass forage (F) to slaughter end weights of 52 (N) or 77 kg (H) on carcass characteristics and organoleptic properties. This experiment included 64 Targhee x Hampshire lambs (average BW = 24 +/- 1 kg) in a 2 x 2 x 2 factorial arrangement of treatments to compare wethers vs. ewes, C vs. F, and N vs. H slaughter weights. No interactions (P > 0.10) were observed between gender and other main effects. Hot carcass weight and dressing percent were greater (P < 0.001) for C- than for F-fed lambs. Backfat thickness also was greater (P < 0.001) for lambs fed C than for those fed F. Moreover, USDA lean quality score and USDA yield grades were higher (P < 0.001) for C- than for F-fed lambs, as well as for lambs slaughtered at H vs. N market weights. There was a higher (P < 0.005) incidence of off odors and off flavors in cooked muscle from F- vs. C-fed lambs, and also from H vs. N slaughter-weight lambs. The heavy C-fed lambs had juicier (P < 0.001) meat than other treatment combinations. Cooked meat from C-fed lambs received higher (P < 0.001) overall acceptability scores. Concentrate-finished lambs produced fatter carcasses and more palatable meat than forage-finished lambs; however, forage finishing allowed for slaughter at heavier weights without excessive fat deposition.

Tissue fatty acid profiles can be used to quantify endogenous rumenic acid synthesis in lambs.

Proportions of vaccenic (trans-11 18:1) and rumenic (cis-9, trans-11 18:2) acids in mesenteric adipose, subcutaneous adipose, and longissimus muscle tissue lipids from lambs fed varying proportions of forages and concentrates were used to develop a mathematical model to predict exogenous and endogenous contributions to rumenic acid (RA) in the several tissues. From the model, we were able to estimate the proportion of absorbed RA, the proportion of vaccenic acid (VA) desaturated, the original proportion of VA in the tissue (before desaturation), and finally the proportion of RA synthesized endogenously. Estimates of endogenous RA were in the range of published data estimated by independent procedures. An independent data set of VA and RA in milk fat was used to challenge the model. Predictions were concordant with observations, although estimates of endogenous RA synthesis were lower than previous reports. Changing the amount of exogenous RA through manipulation of the diet influenced desaturation of VA inversely, so that endogenous RA synthesis was decreased when exogenous supply was increased (r = -0.80). The model should be challenged with data from human and nonruminant, as well as ruminant studies.

Length of docked tail and the incidence of rectal prolapse in lambs.

A multistate cooperative study was conducted to study the current issue of tail length in docked lambs and its relationship to incidence of rectal prolapse. A total of 1,227 lambs at six locations were randomly allocated to two or three tail dock treatments: 1) short--tail was removed as close to the body as possible, 2) medium--tail was removed at a location midway between the attachment of the tail to the body and the attachment of the caudal folds to the tail, and 3) long--tail was removed at the attachment of the caudal folds to the tail. Short-docked lambs had a greater (P < 0.05) incidence of rectal prolapse (7.8%) than lambs with a medium (4.0%) or a long (1.8%) dock. Female lambs had a higher (P < 0.05) incidence of rectal prolapse than male lambs. At two stations, lambs were finished either in a feedlot on a high-concentrate diet or on pasture with no grain supplementation. At one station, with a very low incidence of rectal prolapse, there was no difference in incidence between lambs finished in the feedlot or on pasture; however, at the station with a relatively high incidence of rectal prolapse, lambs in the feedlot had a higher (P < 0.05) incidence than lambs on pasture. The half-sib estimate of heritability for the incidence of rectal prolapse was low (0.14). The results of this study strongly implicate short dock length as a cause of rectal prolapse in lambs finished on high-concentrate diets. Furthermore, the results of this study and the only other study known conducted on this issue strongly suggest that docking lambs at the site of the attachment of the caudal folds to the tail will result in a negligible incidence of rectal prolapse.

Alpha-tocopherol concentrations and case life of lamb muscle as influenced by concentrate or pasture finishing.

Two experiments were conducted to evaluate alpha-tocopherol accumulation in muscle of lambs finished on pasture or concentrates. The objective for Exp. 1 was to compare accumulation of alpha-tocopherol in the longissimus muscle of pasture-fed lambs to that of lambs fed three concentrations (15, 150, and 300 IU/kg of DM) of supplemental vitamin E (all rac alpha-tocopheryl acetate) in all-concentrate diets. The objective in Exp. 2 was to investigate the effect of duration of supplemental vitamin E feeding on alpha-tocopherol content and color change during display case storage of lamb muscle. Treatments evaluated in Exp. 2 were: 15 IU of supplemental vitamin E/kg DM fed to finish; 15 IU/kg followed by 300 IU/kg of DM during the last 21 d; and 15 IU/kg DM until 7 d prior to finish, then 300 IU/kg DM. In Exp. 1, alpha-tocopherol concentration of rotational grazed alfalfa and perennial ryegrass averaged 137 and 169 mg/kg of DM. Vitamin E treatments for lambs fed concentrate diets did not affect ADG (P > 0.15), but ADG was greater (P < 0.01) for concentrate-fed lambs than for grazing lambs. For the concentrate-fed lambs, alpha-tocopherol in longissimus muscle increased quadratically (P < 0.05) as dietary concentrations of vitamin E increased. Predicted maximum alpha-tocopherol concentration in muscle occurred at about 400 IU/kg of diet DM. Longissimus muscle from lambs grazing alfalfa or ryegrass had similar (P > 0.50) alpha-tocopherol concentrations, and those concentrations were similar to values obtained when the concentrate diet supplemented with 150 IU of vitamin E/kg was fed. In Exp. 2, no differences (P > 0.10) in ADG were observed. Concentrations of longissimus alpha-tocopherol were highest when 300 IU supplemental vitamin E was fed for 21 d prior to slaughter. During a 6-d display period, semimembranosus steaks from lambs fed 300 IU of supplemental vitamin E/kg for either 7 or 21 d had higher a* and b* color readings than steaks from lambs fed 15 IU/kg of supplemental vitamin E. Increased consumption of vitamin E either via pasture or supplementation results in higher alpha-tocopherol concentrations in meat.

Scope and limitations of solid-supported liquid-liquid extraction for the high-throughput purification of compound libraries.

This paper reports some of the advantages and limitations of solid-supported liquid-liquid extraction (SLE) for the rapid purification of organic compound libraries. Issues of solvent compatibility, compound compatibility, and technical methods are addressed. In addition the prospective use of calculated log P values is investigated to determine which impurities will be effectively removed by this technique. In addition SLE is shown to be complementary and in some cases superior to solid-phase extraction (SPE) methods for library purification. This is especially true when the desired products have functionality equivalent to that of the impurity to be removed.

Economic burden of influenza-like illness in long-term-care facilities.

Direct medical costs and medically related transportation costs incurred by patients in long-term-care facilities (LTCFs) as a result of influenza-like illness (ILI) were studied. The study was conducted from the payer's perspective. Charts were reviewed retrospectively for all patients who were residents of four Richmond, Virginia, LTCFs between January 1 and May 31, 1999. Consultant pharmacists gathered data on patient demographics, ILI status, vaccination for influenza and streptococcal pneumonia, diagnosis of asthma or chronic obstructive pulmonary disease, and utilization of health care services related to ILI. Services included the use of antimicrobials, antivirals, and respiratory drugs; emergency room visits; diagnostic tests; hospitalizations; and medically related transportation. Costs were based on average wholesale prices (for drugs) and Medicare or Medicaid reimbursement rates. Data were collected for 551 patients. Of these, 112 patients had been diagnosed with 128 cases of ILI during the study period. Twenty-two patients with ILI had 28 visits to emergency rooms, and 30 patients with ILI had 36 hospitalizations. The mean +/- S.D. cost per case of ILI was $1341 +/- $2063; inpatient hospital costs accounted for 84% of this amount. Centers for Disease Control and Prevention criteria for ILI provided a lower incidence of ILI and, consequently, a lower mean +/- S.D. cost of $968 +/- $1806 per case. ILI in patients in four LTCFs in Richmond, Virginia, generated substantial costs, the bulk of which resulted from hospitalization. A substantial percentage of the patients apparently were not immunized.

Recognition instructions and recognition practice can alter the confidence--response time relationship.

Three face-recognition experiments examined how instructions for a recognition test (e.g., emphasize speed or emphasize accuracy) can impact the confidence-response time relationship for episodic memory reports. In all 3 experiments, the confidence-response time correlation was smaller when participants were told to speed up their responding rate, which suggests that participants in these conditions relied less on the artificially compressed response times in forming their confidence judgments than they would under "normal" circumstances. Also, recognition practice before the final memory test eliminated the effect of the recognition instruction manipulation. These results support J. S. Shaw's (1996) suggestion that witnesses rely in part on the fluency of their memory reports when generating confidence judgments, and these findings have important implications for understanding the relationships among witness confidence, accuracy, and response time.

Dolastatin 11, a marine depsipeptide, arrests cells at cytokinesis and induces hyperpolymerization of purified actin.

The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent manner, F-actin was rearranged into aggregates, and subsequently the cells displayed dramatic cytoplasmic retraction. The effects of dolastatin 11 were most similar to those of the sponge-derived depsipeptide jasplakinolide, but dolastatin 11 was about 3-fold more cytotoxic than jasplakinolide in the cells studied. Like jasplakinolide, dolastatin 11 induced the hyperassembly of purified actin into filaments of apparently normal morphology. Dolastatin 11 was qualitatively more active than jasplakinolide and, in a quantitative assay we developed, dolastatin 11 was twice as active as jasplakinolide and 4-fold more active than phalloidin. However, in contrast to jasplakinolide and phalloidin, dolastatin 11 did not inhibit the binding of a fluorescent phalloidin derivative to actin polymer nor was it able to displace the phalloidin derivative from polymer. Thus, despite its structural similarity to other agents that induce actin assembly (all are peptides or depsipeptides), dolastatin 11 may interact with actin polymers at a distinct drug binding site.

IGF-I mRNA and signaling in the diabetic retina.

IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. Because in diabetes vascular and neural cells of the retina undergo accelerated apoptosis, we examined IGF-I synthesis and signaling in the human and rat diabetic retina. In retinas obtained postmortem from six donors aged 64 +/- 8 years with a diabetes duration of 7 +/- 5 years, IGF-I mRNA levels were threefold lower than in the retinas of six age-matched nondiabetic donors (P = 0.005). In the retinas of rats with 2 months' duration of streptozotocin-induced diabetes, IGF-I mRNA levels were similar to those of control rats, but after 5 months of diabetes they failed to increase to the levels recorded in age-matched controls (P < 0.02). Retinal IGF-I expression was not altered by hypophysectomy, proving to be growth-hormone independent. IGF-IR levels were modestly increased in the human diabetic retinas (P = 0.02 vs. nondiabetic retinas) and were unchanged in the diabetic rats. Phosphorylation of the IGF-IR could be measured only in the rat retina, and was not decreased in the diabetic rats (94 +/- 18% of control values). In the same diabetic rats, phosphorylation of Akt was 123 +/- 21% of control values. There was not yet evidence of increased apoptosis of retinal microvascular cells after 5 months of streptozotocin-induced diabetes. Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis.

Body weight and tissue gain in lambs fed an all-concentrate diet and implanted with trenbolone acetate or grazed on alfalfa.

Targhee x Hampshire lambs (average BW 23 +/- 1 kg) were used in two experiments to determine the effects of finishing on concentrate with an anabolic implant or forage grazing after concentrate feeding on growth, organ and viscera weights, and carcass tissue accretion. In Exp. 1 and 2 lambs were penned by sex and assigned for slaughter at initial (23 kg), intermediate (37 kg), or end BW (ewes, 47.7; wethers 50.4 kg). From 23 to 37 kg BW, lambs were fed all-concentrate diets in drylot (DL) or grazed on alfalfa (ALF). Experiment 1 was a 2 x 2 factorial with 28 lambs; factors were wether vs ewe lambs and unimplanted vs DL implanted with trenbolone acetate-estradiol benzoate. There were no differences in organ and viscera weights due to implant status. However, ADG (P < .03) and lean gain (P < .02) were greater for implanted than for unimplanted wethers (507 vs 357 g and 1,314 vs 656 g, respectively). Ewes did not respond to the implant. Fat accretion was not affected by implantation. Experiment 2 was a 2 x 3 factorial with 42 lambs; factors were wether vs ewe lambs and drylot during growing and finishing phases (DL-DL) vs drylot during growing and alfalfa grazing during finishing (DL-ALF) vs alfalfa grazing during growing and finishing phases (ALF-ALF). In Exp. 2, ADG of DL-DL lambs was greater (P < .01) than ADG of DL-ALF or ALF-ALF lambs. Lambs on ALF-ALF had smaller (P < .05) livers and rumen/reticulum weights but heavier (P < .04) kidney, omasum, small and large intestine, and cecum weights than those on DL. In Exp. 2, DL-ALF and ALF-ALF lambs had overall hindsaddle lean gain equal to those on DL-DL with less mesenteric fat and 100 g less separable fat. Finishing lambs on alfalfa reduced fat accretion without decreasing lean accretion, whereas trenbolone acetate implants for lambs fed concentrate increased BW gain and lean accretion without affecting fat accretion.

A phytochemical investigation of Alchornea latifolia.

A phytochemical investigation of the chloroform leaf extract of Alchornea latifolia has been undertaken. Along with the triterpenoids taraxerone, friedelin, epifriedelinol, and taraxerol, the plant also contains seco-3,4-friedelin (dihydroputranjivic acid) (1) and seco-3,4-taraxerone (2). These A-ring-opened triterpenoids show in vitro cytotoxic activity against Hep-G2 and A-431 human cancer cell lines and are potent inhibitors of topoisomerase II.

Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice.

BACKGROUND: Extracellular matrix synthesis and degradation contribute to the morphological changes that occur after myocardial infarction (MI). METHODS AND RESULTS: We tested the hypothesis that inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling in experimental MI. Seventy-one male FVB mice that survived ligation of the left anterior coronary artery were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo by gavage. Echocardiographic studies were performed before randomization (within 24 hours of surgery) and 4 days later and included short-axis imaging at the midpapillary and apical levels. Infarction as defined by wall motion abnormality was achieved in 79% of the procedures (n=56), and mortality rate during the 4-day protocol was 23% (9 of 36 on treatment vs 7 of 35 on placebo; P=NS). Baseline end-diastolic and end-systolic dimensions and areas were similar (P=NS) between treated and placebo groups. At follow-up, infarcted mice allocated to MMP inhibitor had significantly smaller increases in end-systolic and end-diastolic dimensions and areas at both midpapillary and apical levels compared with infarcted mice allocated to placebo (all P<0.05). In addition, infarcted animals that received MMP inhibitor had no change in fractional shortening (-3+/-13%), whereas animals that received placebo had a decrease in fractional shortening (-12+/-12%) (P<0.05). In an analysis stratified by baseline end-diastolic area, the effects of MMP inhibition on the changes in end-systolic area and end-diastolic area were most prominent in animals that had more initial left ventricular dilatation (both P<0.05). CONCLUSIONS: -Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice. Further studies in genetically altered mice and other models will improve understanding of the role of MMPs in left ventricular remodeling.

Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes.

We sought to explore the relationship between receptor tyrosine kinase (RTK) activated signaling pathways and the transcriptional induction of immediate early genes (IEGs). Using global expression monitoring, we identified 66 fibroblast IEGs induced by platelet-derived growth factor beta receptor (PDGFRbeta) signaling. Mutant receptors lacking binding sites for activation of the PLCgamma, PI3K, SHP2, and RasGAP pathways still retain partial ability to induce 64 of these IEGs. Removal of the Grb2-binding site further broadly reduces induction. These results suggest that the diverse pathways exert broadly overlapping effects on IEG induction. Interestingly, a mutant receptor that restores the RasGAP-binding site promotes induction of an independent group of genes, normally induced by interferons. Finally, we compare the PDGFRbeta and fibroblast growth factor receptor 1; each induces essentially identical IEGs in fibroblasts.

Energy source and ionophore supplementation effects on lamb growth, carcass characteristics, visceral organ mass, diet digestibility, and nitrogen metabolism.

In Exp. 1, 72 Targhee lambs (initial BW 22.1+/-.3 kg) were used to determine the effects of energy source (alfalfa pasture vs limit-fed, all-concentrate) and ionophore addition on performance, visceral organ mass, and carcass characteristics. There were no differences (P > . 10) in ADG or gain/ feed due to ionophore supplementation. Lambs that grazed alfalfa had greater (P < .05) liver, omasum, abomasum, small intestine, cecum, and large intestine weights than did lambs fed the concentrate diet. Lambs fed the concentrate diet had greater (P < .01) hot carcass weights, larger (P < .01) loin eye areas, and greater (P < .001) dressing percentages than lambs that grazed alfalfa. In Exp. 2, lambs offered the concentrate diet had greater (P < .001) DM and OM digestibilities than lambs offered alfalfa (89.5 and 91.1 vs 72.4 and 74.2%, respectively). Apparent and true N digestibilities were greater (P < .001) for the concentrate diet than for alfalfa (90.9 and 101.7 vs 77.7 and 91.9%, respectively). Likewise, grams of N retained per day were twice as great (P < .001) with the concentrate diet than with alfalfa (14.9 vs 6.0 g/ d). The greater visceral organ mass and resulting increases in energy and protein requirements in lambs that grazed alfalfa were probably responsible for the lesser hot carcass weight and dressing percentage compared with lambs fed 100% concentrate.