An experiment was conducted to determine the effect of high dietary intakes of Zn and Cu and their combination on growth performance of weanling pigs with diverse health status and management strategies. Twelve experiment stations cooperated and used a total of 1,356 pigs that averaged 6.55 kg BW and 22.2 d age at weaning. The four dietary treatments, all of which met or exceeded NRC requirements, were 1) control, 2) 3,000 ppm Zn (from Zn oxide), 3) 250 Cu ppm (from Cu sulfate), or 4) 3,000 ppm Zn and 250 ppm Cu. The diets were fed as a complex Phase I diet (1.4% lysine) for 7 d followed by a Phase II diet (1.2% lysine) for 21 d. Chlortetracycline (220 ppm) was added to all diets. Fecal color (1 = yellow to 5 = black) and consistency (1 = very firm to 5 = very watery) were scored daily for 3 wk. At the end of the 28-d study, 412 pigs were bled at five stations, and plasma Cu, Zn, and Fe concentrations were determined at one station with atomic absorption spectrophotometry. Average daily gain (375, 422, 409, 415 g/d), feed intake (637, 690, 671, 681 g/d), and gain/feed (586, 611, 611, 612 g/kg) were improved (P < .01) by the addition of Zn and(or) Cu. Significant Cu x Zn interactions imply that the responses to Zn and Cu were independent and not additive. There were significant (P < .01) Zn and Cu effects and a Zn x Cu interaction on fecal color (3.17, 3.24, 4.32, 3.57) and consistency (2.39, 2.14, 2.14, 2.13). Dietary additions of Cu and Zn resulted in elevated plasma concentrations of Cu and Zn, respectively. These data indicate that pharmacological additions of 3,000 ppm Zn (oxide) or 250 ppm Cu (sulfate) stimulate growth beyond that derived from intakes of Zn and Cu that meet nutrient requirements. However, the combination of Zn and Cu did not result in an additive growth response.

Two 15-d nutrient balance trials were conducted using a total of 32 weanling barrows (averaging 6.8 kg, 26 d). The effect of the addition of 15 or 250 ppm Cu (as CuSO4.5H2O) to diets containing 0 or 5% added animal fat on nutrient utilization, digestive enzyme activities, and tissue mineral levels in weanling pigs was investigated. In each trial, four groups of four littermate barrows were randomly assigned to one of four treatments in a 2 x 2 factorial arrangement. The addition of 250 ppm Cu improved apparent fat digestibility and apparent nitrogen retention (P < .02). The addition of 5% fat increased apparent fat digestibility (P < .01). There were no Cu x fat interactions (P > .10) for any of the digestibility indices measured. The addition of 250 ppm of Cu stimulated small intestinal lipase (P < .01) and phospholipase A (P < .05) activities but had no effect (P > .10) on pancreatic lipase or phospholipase activities and no effect on trypsin, chymotrypsin, or amylase activities in the small intestine or the pancreas. The addition of 250 ppm Cu to the diet increased Cu (P < .001) in plasma, liver, and kidney and decreased Fe in plasma (P < .05) and liver (P < .02). The addition of 5% fat increased Fe in kidney (P < .05) and heart (P < .08). Copper x fat interactions were observed for spleen Ca (P < .01), Mg (P < .08), Na (P < .05), and K (P < .08) and spleen weight (P < .05). In additional in vitro assays, increased Cu concentrations tended to consistently stimulate purified porcine pancreatic lipase activity (linear, P < .01) but not purified porcine pancreatic phospholipase A activity (P > .10). The results from this study indicate that 250 ppm Cu stimulated intestinal lipase and phospholipase A activities, leading to an improvement of dietary fat digestibility in weanling pigs.

BackgroundEfforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.MethodsEleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey’s Pair-Wise comparisons.ResultsMRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.ConclusionsThe MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

The effect of addition of 15 or 250 ppm of Cu (as CuSO4.5H2O) and 0 or 5% added animal fat on the utilization of nutrients by weanling pigs was evaluated. Two trials were conducted with four groups of four littermate barrows (6.8 kg, 26 d) in each trial. Dietary treatments were arranged in a 2 x 2 factorial. Data were collected at the beginning of the trial and at the end of each 3-d period. There were no treatment x period interactions (P > .15). There was a Cu level x fat level interaction for ADG (P < .01), feed efficiency (P < .01), N intake (P < .09), fat intake (P < .01), and ash intake (P < .09). Pigs fed 250 ppm of Cu and 5% fat had increased ADG and gain:feed, whereas pigs fed 5% fat and 15 ppm of Cu had decreased ADG and gain:feed compared to pigs fed the other treatments. Apparent digestibility of DM and ash and N retention were increased (P < .05) by the addition of 250 ppm of Cu, whereas the addition of 5% fat decreased (P < .05) DM and ash digestibility. Fat digestibility increased from 28.3% to 75.6% when 5% fat was added to the diet containing 15 ppm of Cu and from 60.8% to 85.1% when 5% fat was added to the diet containing 250 ppm of Cu (Cu level x fat level, P < .01). Pigs fed diets containing 5% fat and 15 ppm of Cu had decreased (P < .06) Na, Cu, Fe, and Zn retention compared to pigs fed the other diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. Wild-type (WT) and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets (NPIs) were studied in non-immunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at one and 24 hours after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages, and platelets. Insulin, complement, antibody, neutrophils, macrophages, and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 hours in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR.

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The present study compared the metabolic response to acute feed deprivation in ovariectomized prepuberal (P; n = 6), 62 +/- 2 kg BW, and mature (M; n = 6) gilts, 124 +/- 4 kg BW. Blood was collected at 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 40, and 48 h after initiation of feeding. Samples were quantified for glucose, insulin, free fatty acids (FFA), beta-hydroxybutyrate (HBA), IGF-I, IGF binding proteins (BP)-1 to -4, cortisol, and amino acids (AA). At 24 h, blood samples were collected every 15 min for 8 h and an additional 1 h after i.v. injection of GnRH (.2 microgram/kg BW) and growth hormone-releasing factor (GRF; 1 microgram/kg BW). Samples were assayed for growth hormone (GH) and LH. Serum insulin concentrations were lower (P < .05) in P gilts. Plasma glucose concentrations were similar. Serum FFA concentrations were greater (P < .05) in P gilts. Serum concentrations of HBA were greater (P < .001) in P gilts at 48 h. Serum IGF-I concentrations were lower (P < .05) in P gilts by 16 h. Serum IGFBP-1-4 levels were similar. Serum cortisol concentrations were similar. Serum concentrations of the essential AA, isoleucine, lysine, threonine, valine, and phenylalanine were greater (P < .05) in P gilts at 40 h. Serum LH concentrations and response to GnRH were similar. Basal serum GH concentrations and peak response to GRF were greater (P < .05) in P than in M gilts. The transition from fed to unfed state occurs more rapidly in P than in M gilts.