Modulation of Synaptic Transmission by Metabotropic Glutamate Receptors and Endocannabinoid Signaling

Metabotropic glutamate receptors (mGluRs) are distributed throughout the central nervous system and play important roles in the modulation of synaptic transmission. The mGluRs regulate long-term potentiation (LTP)/long-term depression (LTD) and learning and memory in hippocampus. This group of glutamate receptors are also reported to exert anticonvulsive and neuroprotective efficacy, especially group I mGluRs. Kindling induced by repeated application of the convulsant pentylenetetrazole (PTZ) is a validated model of epilepsy and epilepsy-related neuromorphological, neurophysiological and behavioural alterations. In this thesis, the role of group I metabotropic glutamate receptors (mGluRs) in PTZ induced seizures, kindling, kindling-related learning deficits and LTP were examined

Effects of dietary Cu, Zn, and ractopamine-HCl on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria

Citation: Feldpausch, J. A., Amachawadi, R., Tokach, M. D., Scott, H. M., Dritz, S. S., Nagaraja, T. G., . . . DeRouchey, J. M. (2016). Effects of dietary Cu, Zn, and ractopamine-HCl on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Journal of Animal Science, 94, 73-74. doi:10.2527/msasas2016-157A total of 480 pigs (PIC 327 × 1050; initially 48.7 kg) were used to determine the interactive effects of supplemental Cu, Zn, and ractopamine HCl on finishing pig growth, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Treatments were arranged in a 2 × 2 × 2 factorial with main effects of added copper (CuSO4; 0 vs. 125 ppm Cu), added zinc (ZnO; 0 vs. 150 ppm Zn) and ractopamine HCl (0 vs. 10 ppm during the last 28 d before marketing; Paylean®; Elanco Animal Health, Greenfield, IN). All diets contained 11 ppm Cu and 73 ppm Zn from the trace mineral premix. Pens of pigs were balanced and blocked on initial BW then randomly allotted to 1 of the 4 mineral treatment diets. Twenty-eight d before marketing, pens within each block and mineral treatment were randomly assigned to receive either 0 or 10 ppm ractopamine in addition to the mineral treatment. Adding either Cu or Zn alone did not improve ADG or ADFI yet resulted in numerical improvements in overall G:F and caloric efficiencies but improvements were not additive (Cu × Zn, P = 0.057, 0.068 and 0.064 for G:F and caloric efficiency on a ME and NE basis, respectively). Ractopamine improved (P < 0.001) overall ADG, G:F, and caloric efficiency thereby increasing final BW by 3% with no change in ADFI. Ractopamine increased (P < 0.001) HCW, percent carcass yield, HCW G:F, loin depth, and percent fat-free lean and decreased (P = 0.014) backfat. An interaction existed whereby adding Zn or Cu alone to diets containing ractopamine numerically improved percent carcass yield and HCW G:F, but no improvement was observed when the Cu or Zn was added to the control diet or when Cu and Zn were fed in combination in the ractopamine diets (Cu × Zn × ractopamine, P = 0.011 and 0.018 for yield and HCW G:F, respectively). Fecal samples were collected on d 0 and at the conclusion of the finishing period (d 90) for bacterial isolation and antimicrobial susceptibility determinations according to minimal inhibitory concentration breakpoints. Escherichia coli and Enterococcus spp. isolates displayed varying levels of resistance to certain antibiotics before initiation of treatments on d 0. Resistance to most antibiotics decreased (P < 0.05) over time or was stable for those that had a low base-line percentage of resistance. Ractopamine and Zn did not adversely affect antimicrobial resistance but extended feeding of 125 ppm Cu throughout the finishing period appeared to antagonize any time-associated decrease in enterococcal resistance to tetracycline, tylosin, and quinupristin/dalfopristin

Effects of dietary copper, zinc, and ractopamine hydrochloride on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria

Citation: Feldpausch, J. A., Amachawadi, R. G., Tokach, M. D., Scott, H. M., Nagaraja, T. G., Dritz, S. S., . . . DeRouchey, J. M. (2016). Effects of dietary copper, zinc, and ractopamine hydrochloride on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Journal of Animal Science, 94(8), 3278-3293. doi:10.2527/jas2016-0340A total of 480 pigs (PIC 327 × 1050; initially 48.7 ± 2.3 kg) were used to determine the interactive effects of supplemental Cu, Zn, and ractopamine HCl (RAC) on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Treatments were arranged in a 2 × 2 × 2 factorial with the main effects of added Cu (CuSO4; 0 vs. 125 mg/kg Cu), Zn (ZnO; 0 vs. 150 mg/kg Zn), and RAC (0 vs. 10 mg/kg during the last 28 d prior to marketing). All diets contained 11 mg/kg Cu and 73 mg/ kg Zn from the trace mineral premix. Pens of pigs were balanced and blocked on initial BW and then randomly allotted to 1 of the 4 mineral treatment diets. At 28 d prior to marketing, pens within each block and mineral treatment were randomly assigned to receive either 0 or 10 mg/kg RAC in addition to the mineral treatment. Adding either Cu or Zn alone did not improve ADG or ADFI yet resulted in numerical improvements in overall G:F and caloric efficiencies, but improvements were not additive (Cu × Zn, P = 0.057, P = 0.068, and P = 0.064 for G:F and caloric efficiency on a ME and NE basis, respectively). Ractopamine improved (P &lt; 0.001) overall ADG, G:F, and caloric efficiency, thereby increasing final BW by 3% with no change in ADFI. Ractopamine also increased (P &lt; 0.001) HCW, percentage carcass yield, G:F, loin depth, and percent fat-free lean and decreased (P = 0.014) backfat. Adding Zn or Cu alone to diets containing RAC numerically improved percent yield and HCW G:F, but this effect was absent when the Cu or Zn was added to the control diet or when Cu and Zn were fed in combination in RAC diets (Cu × Zn × RAC, P = 0.011 and P = 0.018 for yield and HCW G:F, respectively). Fecal samples were collected on d 0 and at the conclusion of the finishing period (d 90) for bacterial isolation and antimicrobial susceptibility determinations according to Clinical and Laboratory Standards Institute minimal inhibitory concentrations breakpoints. Enterococcus spp. and Escherichia coli isolates displayed varying levels of resistance to certain antibiotics prior to initiation of treatments on d 0. Resistance to most antibiotics decreased (P &lt; 0.05) over time or was stable for those that had a low baseline percentage of resistance. Neither Zn nor RAC adversely affected antimicrobial resistance. However, extended feeding of 125 mg/kg Cu throughout the finishing period seems to decrease enterococcal susceptability to tetracycline, tylosin, and quinupristin/dalfopristin. © 2016 American Society of Animal Science. All rights reserved

Evaluation of Clay-Based Binders and In-Feed Antimicrobials on Growth Performance and Biological Measurements in Nursery Pigs

A total of 360 barrows (DNA 200 × 400; initially 14.2 ± 0.08 lb) were used in a 42-d growth study to evaluate clay-based binders or an in-feed antimicrobial on growth performance and biological measurements including fecal and blood analysis in nursery pigs. Pigs were weaned at approximately 21 d of age and randomly allotted to 1 of 4 dietary treatments in a completely randomized design. There were 5 pigs per pen and 18 replications per treatment. Dietary treatments were corn-soybean meal-based and fed in two phases from d 0 to 9 (phase 1) and 9 to 21 (phase 2) after weaning. Either Protek (0.40% of the diet; Nutriquest, Mason City, IA); Protect-8 Plus (0.10% of the diet; Essential Ag Solutions, Sioux Falls, SD); or Kavault (0.04% of the diet; Avilamycin; Elanco, Greenfield, IN) were added to the control diet to create the experimental treatments. A common phase 3 diet was fed to all pigs from d 21 to 42. Overall (d 0 to 42), pigs fed Kavault had increased (P \u3c 0.05) final BW, ADG, and ADFI compared to all other treatments. There was evidence that frequency of fecal scores with softer feces increased over time (P \u3c 0.001), with d 21 having the greatest frequency of diarrhea and soft feces. Fecal Escherichia coli colony count was lower (P \u3c 0.001) on d 21 compared to d 9. For fecal myeloperoxidase (MPO), concentrations were lower (P \u3c 0.05) on d 21 compared to d 6 and 9. For fecal DM, pigs fed Kavault had decreased (P \u3c 0.05) DM percentage compared to all other treatments. Fecal DM percentage was higher (P \u3c 0.05) on d 6 and 9 compared to d 21. No differences (P \u3e 0.10) were observed across treatments for fecal scores, fecal E. coli colony count, fecal MPO or virulence genes associated with E. coli. Similarly, no differences (P \u3e 0.10) were observed across treatments for TNF-alpha and IL-6 blood assays. For IL-6, concentrations were greater (P \u3c 0.05) on d 9 compared to d 21. In summary, pigs fed Kavault had increased BW, ADG, and ADFI, compared to those fed the 2 clay-based additives or the control diet. There were no treatment effects on fecal score, fecal MPO, or blood measurements. However, we observed a day effect indicating that feces were softer and had less DM on d 21 compared to d 6 and 9. Additionally, fecal E. coli colony count and MPO had lower concentrations of d 21 compared to d 9. There was a strong negative correlation between fecal DM and score (P \u3c 0.001) on d 6, 9, and 21 indicating that as fecal DM increased, the score became closer to 0, representing a firmer fecal sample. Fecal DM on d 6 and fecal DM on d 9 were negatively correlated with ADG from d 0 to 9 meaning that as growth rate increased, fecal DM decreased

Effects of Live Yeast and Yeast Extracts with and without Pharmacological Levels of Zinc on Antimicrobial Susceptibilities of Fecal Escherichia coli in Nursery Pigs

A total of 360 weanling barrows (Line 200 × 400, DNA Genetics; initial BW 12.4 ± 0.05 lb) were used in a 42-d study to evaluate yeast-based pre- and probiotics (Phileo by Lesaffre, Milwaukee, WI) in diets with or without pharmacological levels of Zn on antimicrobial resistance (AMR) patterns of fecal Escherichia coli. Pens were assigned to 1 of 4 dietary treatments with 5 pigs per pen and 18 pens per treatment. Dietary treatments were arranged in a 2 × 2 factorial with main effects of live yeast-based pre- and probiotics (none vs. 0.10% ActiSafSc 47 HR+, 0.05% SafMannan, and 0.05% NucleoSaf from d 0 to 7, then concentrations were lowered by 50% from day 7 to 21) and pharmacological levels of Zn (110 vs. 3,000 ppm from d 0 to 7, and 2,000 ppm from d 7 to 21 provided by ZnO). All pigs were fed a common diet from d 21 to 42 post-weaning without live yeast-based pre- and probiotics or pharmacological Zn. Fecal samples were collected on d 4, 21, and 42 from the same three pigs per pen for fecal E. coli isolation. The identification of E. coli was by PCR detection of uidA and clpB genes. The AMR patterns of E. coli were determined by microbroth dilution method using Sensititre CMV3AGNF panel containing 14 different antimicrobials. The addition of pharmacological levels of Zn had a marginally significant effect (P = 0.051) to increase the minimum inhibitory concentration (MIC) values of ciprofloxacin; however, median MIC values were still under the Clinical and Laboratory Standards Institute (2018) classified resistant breakpoint for ciprofloxacin. There was no evidence for differences (P \u3e 0.05) for yeast additives or Zn for AMR of fecal E. coli isolates to any of the remaining antibiotics. In conclusion, pharmacological levels of Zn tended to increase the AMR of fecal E. coli to ciprofloxacin while the medians were below a resistant breakpoint. There was no influence of live yeast and yeast extracts on AMR patterns of fecal E. coli against tested antimicrobials

The Effect of Live Yeast and Yeast Extracts Included in Lactation Diets on Antimicrobial Susceptibility of Fecal Escherichia coli in Sows

A total of 27 sows (Line 241; DNA Genetics) were used in a study to evaluate the effect of feeding live yeast and yeast extracts to lactating sows on antimicrobial susceptibilities of fecal E. coli. Sows were blocked by BW and parity on d 110 of gestation and allotted to 1 of 2 dietary treatments. Dietary treatments consisted of a standard corn-soybean meal lactation diet or a diet that contained yeast-based pre- and probiotics (0.10% Actisaf Sc 47 HR+ and 0.025% SafMannan; Phileo by Lesaffre, Milwaukee, WI). Diets were fed from d 110 of gestation until weaning (approximately d 19). Sow fecal samples were collected to determine the antimicrobial susceptibility of E. coli upon entry into the farrowing house and at weaning for each treatment. The E. coli was isolated from fecal samples, and species confirmation was accomplished by PCR detection of uidA and clpB genes. Microbroth dilution method was used to determine the minimal inhibitory concentrations (MIC) of E. coli isolates to 14 different antimicrobials. Isolates were categorized as either susceptible, intermediate, or resistant based on Clinical and Laboratory Standards Institute guidelines (CLSI, 2018). An interaction (P = 0.026) of diet × sampling day was observed for cefoxitin where fecal E. coli isolates showed no significant differences (P = 0.237) in MIC values at entry, but sows fed the control diet had lower (P = 0.035) MIC values at weaning compared to sows fed yeast additives. There were no significant diet main effects (P \u3e 0.10) on the antimicrobial resistance (AMR) of fecal E. coli. There was an increased (P \u3c 0.02) trend towards resistance for 11 of the 14 antimicrobials over time. Fecal E. coli isolates were resistant to tetracycline and ceftriaxone at weaning. All other isolates were considered susceptible or intermediate across sampling day. In conclusion, feeding live yeast and yeast extracts did not influence either sow or litter performance measurements or the AMR of fecal E. coli during lactation except for cefoxitin, which had a higher MIC at the end of lactation when live yeast and yeast extracts were present in the diet

Evaluation of a Dried Fermentation Product Administered Through Drinking Water on Nursery Pig Growth Performance, Fecal Consistency, and Antibiotic Injections

A total of 350 barrows (DNA Line 200 × 400; initially 13.5 ± 0.02 lb) were used in a 42-d study to evaluate the effects of a dried fermentation product administered through drinking water on nursery pig growth performance, antibiotic injection frequency, fecal consistency, and fecal E. coli presence. Upon arrival to the nursery research facility, pigs were randomly assigned to pens (5 pigs per pen) and pens were allotted to 1 of 2 water treatments with 35 pens per treatment. Water treatments were provided with or without a fermentation product administered through the water lines at a 1:128 dilution rate from d 0 to 14 after weaning. From d 0 to 14, 14 to 42, and for the overall experiment, there was no evidence (P \u3e 0.10) for differences observed for any growth performance criteria. There was evidence (P \u3c 0.05) for day effect on diarrhea presence. Diarrhea presence increased on d 4 and 6, then decreased to low levels. There was no evidence for the fermentation product to influence diarrhea incidence. For antibiotic injections, there was no evidence (P \u3e 0.10) for differences observed between treatments. Mortalities were low, with no evidence (P \u3e 0.10) for differences observed between treatments for removals or mortalities. For fecal dry matter on d 7 and 14, there was no evidence (P \u3e 0.10) for differences observed between treatments. In summary, under these experimental conditions, administering a dried fermentation product for the first 14 d in the nursery through the drinking water did not improve growth performance, fecal dry matter, diarrhea presence, antibiotic injections, or removals and mortalities in nursery pigs. Further evaluation of the dried fermentation product in commercial facilities with greater diarrhea and mortality is needed

Evaluation of a Dried Fermentation Product Administered Through Drinking Water on Nursery Pig Growth Performance, Fecal Consistency, and Antibiotic Injections

A total of 350 barrows (DNA 200 × 400; initially 13.5 ± 0.02 lb) were used in a 42-d study to evaluate the effects of a dried fermentation product administered through drinking water on nursery pig growth performance, antibiotic injection frequency, fecal consistency, and fecal Escherichia coli presence. Upon arrival to the nursery research facility, pigs were randomly assigned to pens (5 pigs per pen) and pens were allotted to 1 of 2 water treatments with 35 pens per treatment. Water treatments were provided with or without a fermentation product administered through the water lines at a 1:128 dilution rate from d 0 to 14 after weaning. From d 0 to 14, 14 to 42, and for the overall experiment, there was no evidence (P \u3e 0.10) for differences observed for any growth performance criteria. There was evidence (P \u3c 0.05) for day effect on diarrhea presence. Diarrhea presence increased on d 4 and 6, then decreased to low levels. There was no evidence for the fermentation product to influence diarrhea incidence. For antibiotic injections, there was no evidence (P \u3e 0.10) for differences observed between treatments. Mortalities were low, with no evidence (P \u3e 0.10) for differences observed between treatments for removals or mortalities. For fecal dry matter on d 7 and 14, there was no evidence (P \u3e 0.10) for differences observed between treatments. In summary, under these experimental conditions, administering a dried fermentation product for the first 14 d in the nursery through the drinking water did not improve growth performance, fecal dry matter, diarrhea presence, antibiotic injections, or removals and mortalities in nursery pigs. Further evaluation of the dried fermentation product in commercial facilities with greater diarrhea and mortality is needed

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient