Activity of ivermectin long-acting injectable (IVOMEC(®) GOLD) in first-season grazing cattle exposed to natural challenge conditions in Germany.

The persistent activity of ivermectin long-acting injection (IVM LAI; IVOMEC® GOLD, Merial; 3.15% ivermectin w/v) against nematode infections of cattle was evaluated under natural challenge conditions. Seventy nematode-free Brown Swiss calves were blocked by pre-treatment bodyweight and allocated randomly to seven groups of 10 animals each: saline (control) at 1 mL/50 kg bodyweight once on day 0 or IVM LAI at 1 mL/50 kg bodyweight (630 mcg IVM/kg) on either days 0, 7, 14, 21, 28, or 35. After housing until day 35, calves were grazed as one herd on a naturally contaminated pasture for 42 days. Calves were then weighed and housed for 4 weeks before being necropsied for parasite counting. Treatment with IVM LAI prevented the establishment (>90%, p < 0.05) of Dictyocaulus viviparus (100%), Bunostomum phlebotomum (100 %), Haemonchus contortus (98.6%), Ostertagia ostertagi/lyrata (94.9%), and Oesophagostomum radiatum (93.3%) for at least 77 days; Ostertagia leptospicularis (99.1%) for 63 days; Cooperia punctata (97.7%), Trichostrongylus axei (96.5%), and Ostertagia spp. inhibited larvae 4 (93.3%) for 56 days; Cooperia oncophora/surnabada (96.9%), Trichuris discolor (93.6%), and Cooperia spp. inhibited larvae 4 (98.8%); and Nematodirus spp. inhibited larvae 4 (97.1%) for 42 days. Calves of groups treated with IVM LAI had significantly (p < 0.001) higher days 0 to 77 weight gains than the saline-treated controls (28.40-39.25 vs 2.60 kg); the weight gains of the IVM LAI-treated groups, however, were not different from one another (p > 0.3). This study demonstrated a very high efficacy of IVOMEC® GOLD in preventing the establishment of a wide range of bovine nematodes for extended periods of time which was associated with a significant benefit to productivity in terms of weight gain.

Actin-dependent motile forces and cell motility.

Force arising from actin polymerization and myosin activity drives a number of different actin-based cell movements. Several new reports support previous data suggesting that actin polymerization drives lamellipodial protrusion and bacterial propulsion, and one report describes a more indirect role for actin assembly in axonal elongation. The major new findings of the past year concerning possible motility roles for myosin describe myosin-driven protrusion of cell margins.

Moving and stationary actin filaments are involved in spreading of postmitotic PtK2 cells.

We have investigated spreading of postmitotic PtK2 cells and the behavior of actin filaments in this system by time-lapse microscopy and photoactivation of fluorescence. During mitosis PtK2 cells round up and at cytokinesis the daughter cells spread back to regain their interphase morphology. Normal spreading edges are quite homogenous and are not comprised of two distinct areas (lamellae and lamellipodia) as found in moving edges of interphase motile cells. Spreading edges are connected to a network of long, thin, actin-rich fibers called retraction fibers. A role for retraction fibers in spreading was tested by mechanical disruption of fibers ahead of a spreading edge. Spreading is inhibited over the region of disruption, but not over neighboring intact fibers. Using photoactivation of fluorescence to mark actin filaments, we have determined that the majority of actin filaments move forward in spreading edges at the same rate as the edge. As far as we are aware, this is the first time that forward movement of a cell edge has been correlated with forward movement of actin filaments. In contrast, actin filaments in retraction fibers remain stationary with respect to the substrate. Thus there are at least two dynamic populations of actin polymer in spreading postmitotic cells. This is supported by the observation that actin filaments in some spreading edges not only move forward, but also separate into two fractions or broaden with time. A small fraction of postmitotic cells have a spreading edge with a distinct lamellipodium. In these edges, marked actin polymer fluxes backward with respect to substrate. We suggest that forward movement of actin filaments may participate in generating force for spreading in postmitotic cells and perhaps more generally for cell locomotion.

Myosin is involved in postmitotic cell spreading.

We have investigated a role for myosin in postmitotic Potoroo tridactylis kidney (PtK2) cell spreading by inhibitor studies, time-lapse video microscopy, and immunofluorescence. We have also determined the spatial organization and polarity of actin filaments in postmitotic spreading cells. We show that butanedione monoxime (BDM), a known inhibitor of muscle myosin II, inhibits nonmuscle myosin II and myosin V adenosine triphosphatases. BDM reversibly inhibits PtK2 postmitotic cell spreading. Listeria motility is not affected by this drug. Electron microscopy studies show that some actin filaments in spreading edges are part of actin bundles that are also found in long, thin, structures that are connected to spreading edges and substrate (retraction fibers), and that 90% of this actin is oriented with barbed ends in the direction of spreading. The remaining actin in spreading edges has a more random orientation and spatial arrangement. Myosin II is associated with actin polymer in spreading cell edges, but not retraction fibers. Myosin II is excluded from lamellipodia that protrude from the cell edge at the end of spreading. We suggest that spreading involves myosin, possibly myosin II.

Sorting during transport to the surface of PC12 cells: divergence of synaptic vesicle and secretory granule proteins.

PC12 cells, a cell line derived from a rat pheochromocytoma, have both regulated and constitutive secretory pathways. Regulated secretion occurs via large dense core granules, which are related to chromaffin granules and are abundant in these cells. In addition, PC12 cells also contain small electron-lucent vesicles, whose numbers increase in response to nerve growth factor and which may be related to cholinergic synaptic vesicles. These could characterize a second regulated secretory pathway. We have investigated the trafficking of protein markers for both these organelles. We have purified and characterized the large dense core granules from these cells using sequential velocity and equilibrium gradients. We demonstrate the copurification of the major PC12 soluble regulated secretory protein (secretogranin II) with this organelle. As a marker for the synaptic vesicle-like organelles in this system, we have used the integral membrane glycoprotein p38 or synaptophysin. We show that the p38-enriched fraction of PC12 cells comigrates with rat brain synaptic vesicles on an equilibrium gradient. We also demonstrate that p38 purifies away from the dense core granules; less than 5% of this protein is found in our dense granule fraction. Finally we show that p38 does not pass through the dense granule fraction in pulse-chase experiments. These results rule out the possibility of p38 reaching the small clear vesicles via mature dense granules and imply that these cells may have two independently derived regulated pathways.

Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force.

We have determined the structural organization and dynamic behavior of actin filaments in entire primary locomoting heart fibroblasts by S1 decoration, serial section EM, and photoactivation of fluorescence. As expected, actin filaments in the lamellipodium of these cells have uniform polarity with barbed ends facing forward. In the lamella, cell body, and tail there are two observable types of actin filament organization. A less abundant type is located on the inner surface of the plasma membrane and is composed of short, overlapping actin bundles (0.25-2.5 microm) that repeatedly alternate in polarity from uniform barbed ends forward to uniform pointed ends forward. This type of organization is similar to the organization we show for actin filament bundles (stress fibers) in nonlocomoting cells (PtK2 cells) and to the known organization of muscle sarcomeres. The more abundant type of actin filament organization in locomoting heart fibroblasts is mostly ventrally located and is composed of long, overlapping bundles (average 13 microm, but can reach up to about 30 microm) which span the length of the cell. This more abundant type has a novel graded polarity organization. In each actin bundle, polarity gradually changes along the length of the bundle. Actual actin filament polarity at any given point in the bundle is determined by position in the cell; the closer to the front of the cell the more barbed ends of actin filaments face forward. By photoactivation marking in locomoting heart fibroblasts, as expected in the lamellipodium, actin filaments flow rearward with respect to substrate. In the lamella, all marked and observed actin filaments remain stationary with respect to substrate as the fibroblast locomotes. In the cell body of locomoting fibroblasts there are two dynamic populations of actin filaments: one remains stationary and the other moves forward with respect to substrate at the rate of the cell body. This is the first time that the structural organization and dynamics of actin filaments have been determined in an entire locomoting cell. The organization, dynamics, and relative abundance of graded polarity actin filament bundles have important implications for the generation of motile force during primary heart fibroblast locomotion.

Tuning the endothelial response: differential release of exocytic cargos from Weibel-Palade bodies.

Essentials Endothelial activation initiates multiple processes, including hemostasis and inflammation. The molecules that contribute to these processes are co-stored in secretory granules. How can the cells control release of granule content to allow differentiated responses? Selected agonists recruit an exocytosis-linked actin ring to boost release of a subset of cargo. SUMMARY: Background Endothelial cells harbor specialized storage organelles, Weibel-Palade bodies (WPBs). Exocytosis of WPB content into the vascular lumen initiates primary hemostasis, mediated by von Willebrand factor (VWF), and inflammation, mediated by several proteins including P-selectin. During full fusion, secretion of this large hemostatic protein and smaller pro-inflammatory proteins are thought to be inextricably linked. Objective To determine if secretagogue-dependent differential release of WPB cargo occurs, and whether this is mediated by the formation of an actomyosin ring during exocytosis. Methods We used VWF string analysis, leukocyte rolling assays, ELISA, spinning disk confocal microscopy, high-throughput confocal microscopy and inhibitor and siRNA treatments to demonstrate the existence of cellular machinery that allows differential release of WPB cargo proteins. Results Inhibition of the actomyosin ring differentially effects two processes regulated by WPB exocytosis; it perturbs VWF string formation but has no effect on leukocyte rolling. The efficiency of ring recruitment correlates with VWF release; the ratio of release of VWF to small cargoes decreases when ring recruitment is inhibited. The recruitment of the actin ring is time dependent (fusion events occurring directly after stimulation are less likely to initiate hemostasis than later events) and is activated by protein kinase C (PKC) isoforms. Conclusions Secretagogues differentially recruit the actomyosin ring, thus demonstrating one mechanism by which the prothrombotic effect of endothelial activation can be modulated. This potentially limits thrombosis whilst permitting a normal inflammatory response. These results have implications for the assessment of WPB fusion, cargo-content release and the treatment of patients with von Willebrand disease.

Role of actin-filament disassembly in lamellipodium protrusion in motile cells revealed using the drug jasplakinolide.

BACKGROUND: In motile cells, protrusion of the lamellipodium (a type of cell margin) requires assembly of actin monomers into actin filaments at the tip of the lamellipodium. The importance of actin-filament disassembly in this process is less well understood, and is assessed here using the actin drug jasplakinolide, which has two known activities - inhibition of filament disassembly and induction of an increase in actin polymer. RESULTS: In cells the two activities of jasplakinolide were found to be separable; 1 microM jasplakinolide could permeate cells, bind cellular filamentous actin (F-actin) and inhibit filament disassembly within 3.5 minutes, but significant increase in actin polymer was not detected until 60 minutes of treatment. In live, permeabilised cells, jasplakinolide did not inhibit filament assembly from supplied, purified actin monomers. In migrating chick fibroblasts, lamellipodium protrusion was blocked within 1-5 minutes of treatment with 1 microM jasplakinolide, without any perturbation of actin organisation. In non-migrating chick fibroblasts, there was a delay in the onset of jasplakinolide-induced inhibition of lamellipodium protrusion, during which lamellipodium length increased linearly with no increase in protrusion rate. Motility of the bacterium Listeria in infected PtK2 cells was reduced 2.3-fold within 3 minutes of treatment with 1 microM jasplakinolide. CONCLUSIONS: Actin-filament disassembly is tightly coupled to lamellipodium protrusion in migrating chick fibroblasts and motility of Listeria in PtK2 cells. One simple interpretation of these data is a situation whereby ongoing actin-filament assembly uses free actin monomer derived from filament disassembly, in preference to stored monomer.

An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism.

BACKGROUND: Simple epithelia encase developing embryos and organs. Although these epithelia consist of only one or two layers of cells, they must provide tight barriers for the tissues that they envelop. Apoptosis occurring within these simple epithelia could compromise this barrier. How, then, does an epithelium remove apoptotic cells without disrupting its function as a barrier? RESULTS: We show that apoptotic cells are extruded from a simple epithelium by the concerted contraction of their neighbors. A ring of actin and myosin forms both within the apoptotic cell and in the cells surrounding it, and contraction of the ring formed in the live neighbors is required for apoptotic cell extrusion, as injection of a Rho GTPase inhibitor into these cells completely blocks extrusion. Addition of apoptotic MDCK cells to an intact monolayer induces the formation of actin cables in the cells contacted, suggesting that the signal to form the cable comes from the dying cell. The signal is produced very early in the apoptotic process, before procaspase activation, cell shrinkage, or phosphatidylserine exposure. Remarkably, electrical resistance studies show that epithelial barrier function is maintained, even when large numbers of dying cells are being extruded. CONCLUSIONS: We propose that apoptotic cell extrusion is important for the preservation of epithelial barrier function during cell death. Our results suggest that an early signal from the dying cell activates Rho in live neighbors to extrude the apoptotic cell out of the epithelium.

Investigation of the mechanism of retraction of the cell margin and rearward flow of nodules during mitotic cell rounding.

We have studied two types of cell motility directed toward the cell center: retraction of the cell margin and rearward flow of small cytoplasmic nodules during mitotic cell rounding in Potoroo tridactylis kidney (PtK2) cells by time-lapse video microscopy, drug treatments, and photoactivation of fluorescence. Nodules flow rearward on thin, actin-rich fibers (retraction fibers) exposed as the cell margin retracts. Retraction of the cell margin and rearward flow of nodules require intact actin filaments, but are insensitive to an inhibitor of myosin function (butanedione monoxime). Using photoactivation of fluorescence marking, we have determined that actin filaments in the majority of retraction fibers remain stationary while the cell margin retracts and nodules flow rearward. The pointed ends of retraction fiber actin filaments face the cell center. We argue that nodule motility is driven by a novel actin-based force that perhaps also partially contributes to retraction of the cell margin during cell rounding at mitosis.

Age and adjuvant chemotherapy use after surgery for stage III colon cancer.

BACKGROUND: Randomized trials have established that 5-fluorouracil-based adjuvant chemotherapy following resection of stage III colon cancer reduces subsequent mortality by as much as 30%. However, the extent to which adjuvant therapy is used outside the clinical trial setting, particularly among the elderly, is unknown. METHODS: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results/Medicare-linked database identified 6262 patients aged 65 years and older with resected stage III colon cancer. The primary outcome was chemotherapy use within 3 months of surgery, as ascertained from Medicare claims. We examined the extent to which age at diagnosis was associated with adjuvant chemotherapy usage, and we adjusted for potential confounding based on differences in other patient characteristics with the use of multiple logistic regression. All P values were two-sided. RESULTS: Age at diagnosis was the strongest determinant of chemotherapy: 78% of patients aged 65-69 years, 74% of those aged 70-74 years, 58% of those aged 75-79 years, 34% of those aged 80-84 years, and 11% of those aged 85-89 years received postoperative chemotherapy. The age trend remained pronounced after adjustment for potential confounding based on variation in patients' demographic and clinical characteristics and after exclusion of patients with any evident comorbidity (all P values <.001). CONCLUSIONS: Adjuvant chemotherapy for stage III colon cancer is used extensively, especially for patients under the age of 75 years. However, treatment rates decline dramatically with chronologic age. Because patients in their 70s and even 80s have a reasonable life expectancy, further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding this potentially curative treatment.

Organization and polarity of actin filament networks in cells: implications for the mechanism of myosin-based cell motility.

Force arising from myosin activity drives a number of different types of motility in eukaryotic cells. Outside of muscle tissue, the precise mechanism of myosin-based cell motility is for the most part theoretical. A large part of the problem is that, aside from cell surface features such as lamellipodia and microvilli, relatively little is known about the structural organization of potential actin substrates for myosin in non-muscle motile cells. Several groups [Cramer, Siebert and Mitchison (1997) J. Cell Biol. 136, 1287-1305; Guild, Connelly, Shaw and Tilney (1997) J. Cell Biol. 138, 783-797; Svitkina, Verkhovsky, McQuade and Borisy (1997) J. Cell Biol. 139, 397-415] have begun to address this issue by determining actin organization throughout entire non-muscle motile cells. These studies reveal that a single motile cell comprises up to four distinct structural groups of actin organization, distinguished by differences in actin filament polarity: alternating, uniform, mixed or graded. The relative abundance and spatial location in cells of a particular actin organization varies with cell type. The existence in non-muscle motile cells of alternating-polarity actin filament bundles, the organization of muscle sarcomeres, provides direct structural evidence that some forms of motility in non-muscle cells are based on sarcomeric contraction, a recurring theory in the literature since the early days of muscle research. In this scenario, as in muscle sarcomeres, myosin generates isometric force, which is ideally suited to driving symmetrical types of motility, e.g. healing of circular wounds in coherent groups of cells. In contrast, uniform-polarity actin filament bundles and oriented meshworks in cells allow oriented movement of myosin, potentially over relatively long distances. In this simple 'transport-based' scenario, the direction in which myosin generates force is inherently polarized, and is well placed for driving asymmetrical or polarized types of motility, e.g. as expected for long-range transport of membrane organelles. In the more complex situation of cell locomotion, the predominant actin organization detected in locomoting fish keratocytes and locomoting primary heart fibroblasts excludes sarcomeric contraction force from having a major role in pulling these cell types forward during locomotion. Instead Svitkina et al. propose that 'dynamic network contraction' of a weakly adherent uniform-polarity actin filament meshwork is the basis of keratocyte locomotion. For fibroblast locomotion, however, Cramer et al. prefer a transport mechanism based on graded-polarity actin filament bundles.

Molecular mechanism of actin-dependent retrograde flow in lamellipodia of motile cells.

In motile, eukaryotic cells, a variety of cell-associated material (collectively termed here as 'particles') continuously flows, relative to the substratum, from the front to the back of the extreme margin of the cell (termed the 'lamellipodium'). This retrograde particle flow, occurs both over the surface of, and inside the lamellipodium. Force to drive retrograde particle flow in lamellipodia is dependent on actin filaments, but the precise mechanism of force generation, and function of the flow is generally not well understood. Actin filaments themselves, in lamellipodia of most motile cell types studied also flow retrograde relative to the substratum. This actin flow, in Aplysia bag cell neuronal growth cones, is known to be driven by activity of a myosin. In these growth cones, retrograde flow of cell surface-attached particles is coupled to retrograde actin flow. In Aplysia, force from retrograde actin flow may limit certain types of growth cone motility. In other motile cell types, such as keratocytes and fibroblasts, the mechanism of retrograde particle flow and function of retrograde actin flow in lamellipodia is poorly understood. For these cell types, recent data provide a basis for proposing alternative actin-based mechanisms to drive retrograde particle flow in lamellipodia. One mechanism is based on activity of a putative pointed end- directed actin motor, and the other on tension-driven surface lipid flow. Here I will review recent advances that have been made in determining the molecular mechanism of force generation to drive retrograde particle flow relative to the substratum in lamellipodia of motile cells. I will address the function of retrograde actin flow in lamellipodia, and apparent differences between Aplysia and other motile cell types.

Manifest refraction versus autorefraction for patients with subfoveal choroidal neovascularization.

PURPOSE: To compare the results from manifest refraction using trial lenses and a standard visual acuity protocol to results from autorefraction for obtaining refractive error and best corrected visual acuity in patients enrolled in a randomized clinical trial. METHODS: During a 4-month period, 29 patients with subfoveal choroidal neovascularization (CNV), who were enrolled in the Submacular Surgery Trials (SSTs) Pilot Study at the Wilmer Ophthalmological Institute, gave verbal consent to participate in this study. Best corrected visual acuity was obtained using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and standardized room lighting after performance of manifest refraction, according to the SST protocol, and autorefraction. Refractive error (spherical equivalent) and visual acuity scores were obtained in both eyes of all patients. RESULTS: On average, manifest refraction gave a spherical equivalent that was 1.04 D more plus than autorefraction (95% limits of agreement = 0.74, 1.34). On average, the visual acuity score was 1.5 letters better after manifest refraction than after autorefraction (95% limits of agreement = 0, 3.0). The comparison of the two methods of refraction was subdivided according to visual acuity level and eye disease (age-related macular degeneration or ocular histoplasmosis syndrome). CONCLUSIONS: Despite large differences in spherical equivalent between manifest refraction and autorefraction, the visual acuity scores were close (mean difference, 1.5 letters). Other studies comparing subjective refraction and autorefraction have shown similar results. Autorefraction in patients with subfoveal CNV may be a satisfactory alternative to manifest refraction in clinical trials and field studies in which best corrected visual acuity is of interest.

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors.

Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or non-biopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m2 BCNU, 900 mg/m2 thiotepa and 1500 or 750 mg/m2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both newly diagnosed and recurrent CNS tumors.

The role of attributions in the development of dating relationships.

In this study, we examine the role of attributions in the context of dating relationships. A large sample completed a questionnaire comprising structured ratings and a free-response relationship description. As expected, cognitive or attributional activity was more frequent within relationships when they were in the early stages, when important choice points or changes were occurring, and when the relationships were perceived as unstable. Also as predicted, subjects who reported higher relationship happiness, commitment, and love for their partners tended to describe the relationship in more interpersonal terms, to rate the causal inputs of the partners as equal, and to attribute lower external attributions for relationship maintenance. Finally, some evidence was obtained that attributions for relationship maintenance are causally related to relationship happiness over a 2-month period. The results are discussed in terms of the relationship between cognitive processing and the development of dating relationships.

Facial resurfacing with the Limberg flap.

The Limberg flap is a valuable tool in teaching the art of local flap design. It is a very versatile addition to the armamentarium of any surgeon which provides a precise mathematical design for closure of both the primary and the secondary (donor) defect. The lines of maximum extensibility of the skin are crucial in the design of the rhomboid and the flap. Attention to these details avoids complications and assures good aesthetic and functional results.

Effects of psoroptes ovis infection and its control with an ivermectin controlled-release capsule on growing sheep. 1. Evaluation of weight gain, feed consumption and carcass value.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg per day for 100 days. The lambs were infested with 50-60 P. ovis mites each on Days 14 and 21. Mites in skin scrapings were counted on Days 70, 84, 98, 112 and 126. Body weight and feed consumption were measured every 2 weeks from Day 0 to 126. The animals were slaughtered on Day 127 and their carcasses evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs treated on Day 0 had significantly (p<0.05) greater body weight gain from Day 0 to 84 (13.9 kg) and Day 0 to 126 (20.9 kg) than the untreated controls (9.6 and 12.8 kg, respectively) and the sheep treated on Day 84 (8.4 and 14.9 kg, respectively). Feed consumption (Days 0-126) for sheep treated with the IVM-CRC on Day 0 was higher than for sheep treated on Day 84 (p<0.05) and for the untreated controls (p<0.1). The carcasses of sheep treated with the IVM-CRC on Day 0 had significantly (p<0.05) higher warm and cold weights, carcass yield, rib eye area and back fat thickness than the untreated control group and the sheep treated with the IVM-CRC on Day 84. The sheep treated with the ivermectin CRC on either Day 0 or 84 had significantly (p<0.05) better muscle scores and lower muscle pH 1h post-slaughter than the untreated controls. There was no significant (p>0.1) difference between warm and cold carcass weights, carcass yield and rib eye area between sheep treated on Day 84 and untreated controls.