Effects of spantide ([D-Arg1,D-Trp7,9,Leu11]substance P) on coronary resistance vessels were studied in isolated guinea pig hearts perfused at constant rate with isotonic buffer containing 20 or 40 mM KCl. Spantide (1 μM) caused a 20-fold rightward shift of the substance P (SP) dose-response curve for vasodilation with no change in maximum (KB=5.3×10-8 M). Bolus injections of 0.25 to 250 pmol spantide had no effect, but higher doses caused a brief vasodilation followed by a larger, more prolonged vasoconstriction. Histamine produced similar changes in perfusion pressure. Antihistamines (H1 and H2) reduced or blocked responses to spantide and histamine. These findings indicate spantide is a competitive antagonist to SP in guinea pig coronary resistance vessels. In addition, high doses of spantide can cause prominent vascular effects which are mediated by histamine.

The parmacological effects of guinea pig vasoactive intestinal peptide (VIP) were studied in isolated perfused guinea pig hearts. Bolus injections of VIP produced a dose-dependent tachycardia that was not affected by atenolol. A decrease in amplitude of ventricular contractions occurred in response to all doses of VIP. This response was preceded by a small increase in amplitude in 3 of 6 hearts at the highest dose. VIP produced a decrease in perfusion pressure which was prominent after coronary tone was elevated with [Arg8]-vasopressin. The present findings support speculation that VIP may have a role in the regulation of heart rate and coronary blood flow.

Objective: The aim of this study was to investigate inherent in vitro permeability, metabolism, and cytotoxicity of idebenone - an active used to protect skin as an anti-aging agent -and compare it to idebenone linoleate. Methods: Idebenone and idebenone linoleate were investigated in pig ear skin and melanoma (B16: F10 mouse) cells. Diffusion experiments were conducted at 37 °C (bath temperature) using Franz diffusion cells. Authentic metabolite samples were synthetically prepared. Samples were analyzed using liquid chromatography-mass spectrometry/mass spectrometry. Cell viability was determined via the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: Idebenone was shown to permeate across viable porcine ear tissue; there was no evidence that idebenone linoleate permeated across porcine ear tissue after 4 h. Idebenone was metabolized to idebenone acid in both pig ear and mouse melanocytes; only minor idebenone linoleate metabolism was observed. Idebenone displayed delayed in vitro toxicity (via MTT assay) in melanocytes, while idebenone linoleate displayed no such in vitro toxicity. Conclusions: The in vitro metabolism and cytotoxicity results suggest that metabolic activation of idebenone is the likely culprit that activates the skin irritation mechanism via idebenone in vivo usage. An idebenone ester (e.g. idebenone linoleate) appears to provide a superior in vitro safety profile over idebenone.

The presence of vasoactive intestinal polypeptide (VIP) has been analyzed in fibers and neurons within the guinea pig intrinsic cardiac ganglia and in fibers innervating cardiac tissues. In whole-mount preparations, VIP-immunoreactive (IR) fibers were present in about 70% of the cardiac ganglia. VIP was co-localized with neuronal nitric oxide synthase (nNOS) in fibers innervating the intrinsic ganglia but was not present in fibers immunoreactive for pituitary adenylate cyclase-activating polypeptide, choline acetyltransferase (ChAT), tyrosine hydroxylase, or substance P. A small number of the intrinsic ChAT-IR cardiac ganglia neurons (approximately 3%) exhibited VIP immunoreactivity. These few VIP-IR cardiac neurons also exhibited nNOS immunoreactivity. After explant culture for 72 h, the intraganglionic VIP-IR fibers degenerated, indicating that they were axons of neurons located outside the heart. In cardiac tissue sections, VIP-IR fibers were present primarily in the atria and in perivascular connective tissue, with the overall abundance being low. VIP-IR fibers were notably sparse in the sinus node and conducting system and generally absent in the ventricular myocardium. Virtually all VIP-IR fibers in tissue sections exhibited immunoreactivity to nNOS. A few VIP-IR fibers, primarily those located within the atrial myocardium, were immunoreactive for both nNOS and ChAT indicating they were derived from intrinsic cardiac neurons. We suggest that, in the guinea pig, the majority of intraganglionic and cardiac tissue VTP-IR fibers originate outside of the heart. These extrinsic VIP-IR fibers are also immunoreactive for nNOS and therefore most likely are a component of the afferent fibers derived from the vagal sensory ganglia.

Dietary inclusion of sufficient lysine is very critical for optimizing pig’s growth performance. The objectives of this project were to study the effects of dietary lysine at different concentrations on (1) the growth performance and carcass characteristics, (2) the muscle gene expression profile and the possible alterations to the metabolic and signaling pathways, (3) the muscle fatty acid profile, and (4) the plasma concentrations of growth-related hormones of late-stage finishing pigs. Nine crossbred barrows were assigned to 3 dietary treatments (lysine-deficient, equate, and -excess diets) according to a completely randomized experimental design. During the 5-week feeding trial, pigs were allowed ad libitum access to experimental diets and water. All pigs and experimental diets were weighed individually each week during feeding trial to determine growth performance. After harvest, the carcass characteristics were determined and muscle samples were collected from longissimus dorsi for mRNA and fatty acid profiling, while the jugular vein blood was collected at the end of four weeks for analyses of three growth-related hormones. While the average daily gain showed a quadratic relationship, the dressing percentage and total lean cut weight both increased linearly with dietary lysine concentrations. Results of muscle gene expression data showed that dietary lysine deficiency may lead to decreased protein synthesis, increased protein degradation and lipid accumulation, while dietary lysine excess may lead to decreased protein degradation and increased lipid biosynthesis. Fatty acid (FA) composition data showed that different dietary lysine concentrations altered the intramuscular fat (IMF) content and FA composition, especially the unsaturated FAs. In particular, dietary lysine deficiency increased the IMF content and the proportion of mono-unsaturated FAs. Hormone analyses showed that the plasma concentrations of insulin and growth hormone were not affected by dietary lysine, whereas the concentration of insulin-like growth factor 1 was decreased by either dietary lysine deficiency or excess. Collectively, lysine may function as a signaling molecule to regulate the expression of genes related to protein turnover and lipid metabolism in the muscle of finishing pigs, causing differences in growth performance, carcass characteristics, and FA composition. IGF-1 may be a controlling growth factor that is sensitive to dietary lysine.

The most widely used process to reduce iron ore and to produce pig iron is the blast furnace. The blast furnace is a large source of CO2 emissions since it is a coal based process and due to that the main energy source and reducing agent is coke, it is difficult to reduce these further. IRONARC is a new method used to produce pig iron by reducing iron ore and all the energy used for heating comes from electricity, which gives the opportunity to use renewable resources. The process uses plasma generators that inject gas at high temperature and velocity into a slag that consists of iron oxides. The iron oxides are reduced in two steps that appear by using gas as reduction agent in the first step and carbon in the second step.   It exists in a smaller pilot plant scale and this project was the first step in the future upscaling of the IRONARC process. Computational Fluid Dynamics (CFD) modelling was used and the goal was to determine the penetration depth of the IRONARC pilot plant process by numerical simulation in the software ANSYS FLUENT. The penetration depth is of importance because to be able to scale up the process it is important to know the flow pattern and the structure of the flow in the process, which is dependent on how far into the slag the gas reaches. Two numerical models were made. First an air-water model that described the initial penetration of air injected into water. The air-water simulation was made with parameters and data from an experiment found in literature. This was done to build an accurate CFD model for the penetration depth in FLUENT and validate the model with the results of the penetration depth from the experiment. The air-water simulation gave good and promising results and yielded the same result regarding the penetration depth as the experiment.  The model for the penetration depth was then used with the IRONARC geometry and parameters. After simulation the penetration depth of the IRONARC process was determined. For the future, the penetration depth of the pilot plant needs to be measured and compared with the simulated result for the penetration depth.

<p>Gastrointestinal health in the young pig is a constant challenge for the swine industry. Weaning introduces many stressors such as a new solid diet, being separated from their mother, new pen mates, transportation, and an entirely new environment. Therefore, this dissertation primarily focuses on research aiding the pig immediately post-weaning. In chapter 2, a developmental bacillus direct fed microbial (DFM) was added to nursery pig diets to evaluate its effects on pig growth and health in two 35-d experiments, both randomized complete block designs based on initial BW and sex. Experiment 1 used 376 weaned pigs (17.8 d of age; 5.99±0.18 kg initial BW) allotted to one of four diets. 1) Negative Control (NC; no antibiotics with pharmacological Zn or Cu), 2) NC+DFM 0.275x109 CFU, 3) NC+DFM 0.55x109 CFU, 4) NC+DFM 1.1x109 CFU. Experiment 2 used 420 weaned pigs (20.1 d of age; 6.11±0.34 kg initial BW) allotted to one of four diets: 1) Negative Control (NC; no antibiotics with pharmacological Zn or Cu), 2) NC+DFM 0.55x109 CFU, 3) NC+DFM 1.1x109 CFU, 4) NC+BioPlus 2B 1.1x109 CFU. Experiment 1; during week 1 there were no treatment effects. During week 3 ADFI (P=0.053) quadratically increased while G:F (P=0.028) quadratically decreased as DFM increased in the diet. During d21-35 of experiment 2, ADG (P=0.092) quadratically increased and G:F (P=0.014) quadratically decreased as DFM increased.  Overall, for Experiment 1, ADFI numerically increased (4.3%) with no increase in ADG, resulting in a quadratic decrease in G:F (P=0.010) as the DFM increased in the diet.  For Experiment 2, during week 1, DFM fed pigs tended to have linearly decreased ADFI (P=0.092) and linearly increase G:F (P=0.072). Pigs fed the Bioplus2B bacillus had greater ADFI (P=0.018) than the same dose of the experimental bacillus. During week 2 pigs fed the experimental bacillus at 1.1x109 CFU tended to have improved G:F (P=0.084) than the similar DFM concentration from, the Bioplus 2B. During week 4 ADG tended to linearly (P=0.057) improve with increasing DFM in the diet and the average of all DFMs tended to have improved ADG (P=0.075) over the NC. During week 5 ADFI linearly increased (P=0.029) as DFM increased in the diet and all DFM treatments had greater ADFI (P=0.009) than the NC.  During d 21-35 of experiment 2, DFM fed pigs had linearly increased ADG (P=0.04) and ADFI (0.090). All pigs fed DFM had improved ADG (P=0.068) and ADFI (P=0.032) compared to NC fed pigs. Summarizing these two studies, the DFM product had its greatest effect improving gain feed intake and efficiency during late nursery when simplest diets are fed.</p> <p>In chapter 3, Dacitic tuff breccia (DTB) and poultry by-products (PBP) were added to nursery pig diets to evaluate their effects on growth performance and jejunal characteristics in a 35 d experiment. PBP were added as a replacement for fishmeal and was expected to provide an increased immune challenge to the newly weaned pigs. DTB was added as a functional trace element source and was hypothesized to ameliorate some of the negative impacts of PBP on the gut. A randomized complete block design based on BW and sex was used. Newly weaned pigs (N=564, 20.1±1.2 d of age, 6.18±1.13 kg initial BW). allotted to four diets (15 replicates/treatment; 9 or 10 pigs/pen): 1) Control (C; no DTB or PBP), 2) C+DTB (0.5% inclusion), 3) C+PBP (4% chicken by-product meal + 2% feather meal – replacing fishmeal, corn, and synthetic amino acids in the C), 4) C+DTB+PBP. Phase 1-3 were each 7-d and Phase 4 was from d 21-35. One barrow/pen was harvested 11d post-weaning. Jejunal tissue and mucosa were collected for histological measures and gene expression. In week 2, pigs fed DTB tended to increase ADG (323 vs. 303 g/d; P=0.068) and ADFI (376 vs. 356 g/d; P=0.055) compared to pigs not fed DTB and pigs fed PBP tended to have increased ADG (P=0.093). In week 3 pigs fed PBP had reduced ADG (460 vs 483 g/d; P=0.011) and G:F (0.689 vs. 0.723; P<0.001), and there tended to be an interaction for G:F (P=0.083) with DTB improving G:F when fed in combination with PBP but reducing G:F in the control diet.  In week 4, feeding PBP decreased ADG (384 vs 415 g/d; P<0.01) and ADFI (629 vs 666 g/d; P<0.01) compared to pigs fed no PBP.  For Phase 4 (d21-35) pigs fed PBP had decreased ADG (479 vs 497 g/d; P=0.041) and tended to have reduced ADFI (P=0.092) compared to pigs fed no PBP. Overall (d 0-35), there were no significant differences among treatments in pig growth performance.   Pigs fed PBP had increased jejunal expression of interferon-alpha (P=0.041) and interleukin-10 (P=0.037) and tended to have increased expression of claudin-1 (P=0.076).  Pigs fed DTB tended to have decreased jejunal expression of interferon-gamma (P=0.079).  Jejunal gene expression of tumor necrosis factor-alpha and nuclear factor kappa-beta did not differ among treatments. In conclusion, DTB improved nursery pig growth performance early and pigs fed PBP had decreased ADG and feed efficiency late in the nursery period. Feeding PBP had minimal effects on jejunum architecture but increased the gut immune response.</p> <p>Chapter 4 focuses on weaning age in addition to dietary treatments. Changes in weaning age and diet complexity can impact pig growth post-weaning. 432 weanling gilts and barrows (Topigs Duroc Ⅹ (US York X Landrace)) from the same farrowing group were utilized for a 30 or 35 d growth trial to compare early (EW) versus late weaning (LW) and high or low levels of specialty proteins in nursery diets. 216 pigs were EW (18 or 19 d, avg. age=18.4 days, avg. BW=5.96 kg) and 216 pigs were LW 5 days later (24, 25 or 26 d, avg. age=24.6 d, avg. BW=7.50 kg). At weaning pigs were blocked by weaning age, BW, sex and litter, and randomly allotted to 48 pens with 9 pigs/pen. Pigs at each weaning age were fed a High Complexity (HC) or a Low Complexity (LC) diet. The trial was conducted as a 2X2 factorial design: 1) EW+HC; 2) EW+LC; 3) LW+HC; 4) LW+LC. Pigs and feeders were weighed on d 0, 7, 14, 21, 28, and 35 for EW, and on d 0, 7, 14, 21, 28, and 30 for LW.  LW pigs had improved ADG and ADFI from d 0-7, 7-14, 14-21, and the final week of the nursery (P<0.05). G:F decreased for LW pigs from d 21-28 (P<0.01) compared to EW pigs, however for the overall nursery trial LW pigs had increased G:F (P=0.01). LW pigs had increased overall nursery ADG vs EW pigs (452.5 g/d vs 400 g/d; P<0.01). End of nursery BW was greater for LW vs EW pigs (21.70 kg vs 20.74 kg; P=0.001).  There was a weight block by weaning age interaction, EW heavy pigs had lower ADG compared to LW heavy pigs, however when comparing light weight pigs, the EW light pigs had improved ADG compared to LW light weight pigs (P=0.017). EW pigs were lighter at market (approximately d146 of age) compared to LW pigs (120.78 vs 124.16 kg; P=0.014). An interaction between weaning age, nursery diet, and sex (P<0.07) was observed for market weight, EW barrows fed LC diets were lighter at market (120.77 kg) than EW barrows fed HC diets (126.54 kg).  Whereas for LW barrows fed LC had higher market weights (130.04 kg) than LW barrows fed HC diets (127.59 kg). A similar, but non-significant pattern was observed for gilts. Weaning age and feeding pigs the correct diet for their age in the nursery can have a lifelong effect on the pig. </p> <p>In conclusion, feeding a DFM containing bacillus licheniformis did not impact nursery pig growth performance early in the nursery period. From d21-35 ADG and ADFI was improved in both experiments 1 and experiment 2. While the growth results were sporadically improved throughout the nursery period, the DFM’s greatest effect was it ability to improve ADFI. The improvement in the late nursery phase may be due to the need for the DFM to establish itself in the GIT. DTB tended to improve ADG and ADFI in week 2 of the nursery period, however there were no differences for growth overall. PBP reduced ADG in week 3 of the nursery period, as well as reduced ADG and ADFI in week 4 of the nursery. While there were differences in individual weeks of the trial there were no overall differences in growth performance. However, when looking at gene expression in the jejunum at d11 post-weaning, there was an increase in IFN-α and IL-10 in pigs fed PBP. In pigs fed DTB there was a decrease in IFN-γ jejunal gene expression as well. Feeding a high complexity and low complexity diet had no impact on the nursery pigs growth performance, in hindsight the low complexity diet was perhaps not low enough in specialty proteins. When comparing weaning age, pigs weaned later had increased ADG and ADFI from d0-21 post-weaning. For the overall nursery performance, LW pigs had a higher ADG, and ended the nursery period 0.96 kg heavier than the EW pigs. Comparing pigs of similar bodyweight at weaning, EW pigs were 1.5 kg heavier than LW pigs at the end of the nursery period, but the LW pigs were more feed efficient. There was a weight block by weaning interaction in this trial, as the heaviest LW pigs had higher ADG compared to the heaviest EW pigs. However, when looking at the lightest pigs, the EW pigs outperformed the LW pigs. Looking at market weights of each age group, LW pigs were 3.5 kg heavier on average at d146 of age. Although there was not a difference in diet found in the nursery phase, interestingly there were interactions discovered between treatments at market weight. Barrows are more sensitive to nursery diet compared to gilts, as LW barrows fed the low complexity diet performed better than the LW high complexity fed barrows. EW barrows were heavier at market when fed the high complexity diet, compared to EW barrows fed the low complexity diet. This shows that while the diet didn’t appear to have an impact in the nursery, feeding the pig the proper diet for their age has a lifelong impact on the pig.</p>

No description available.

Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to investigate the effect of partial substitution of dietary lard by an isocaloric amount of olive or coconut oil on endpoints of NAFLD. Thirty-eight 15-d-old Iberian pigs housed in pens balanced for weight and sex were randomly assigned to receive 1 of 3 hypercaloric high-fructose high-fat (HFF) diets for 10 weeks: 1) lard (LAR; n=5 pens), 2) lard + olive oil (OLI, n=10), and 3) lard + coconut oil (COC; n=10). Additional pigs (BSL, n=4) were fed a eucaloric diet to establish baseline values. Animals were euthanized at 85 d of age after blood sampling. Liver tissue was collected for histology, metabolomics, and transcriptomics. Compared with BSL, OLI decreased high-density lipoproteins, phosphatidylcholines (PC), and total cholesterol in blood, and increased acylcarnitines in liver, whereas COC increased triacylglycerides (TAGs) in liver and blood. All HFF diets increased bile acids in liver, and decreased choline and fibroblast growth factor 19 in liver and blood. OLI and COC increased hepatic steatosis, necrosis, ballooning, and composite lesion score compared with LAR. OLI decreased gene expression of carnitine O-palmitoyltransferase 1, and COC increased expression of fatty acid binding proteins and acyl-CoA synthetase. In conclusion, partial replacement of dietary lard with olive and coconut oil dysregulated acylcarnitine metabolism and lipogenesis in the liver, increasing the severity of NAFLD in juvenile pigs.

Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter of the central and peripheral nervous systems, predominantly secreted in the gastrointestinal tract, especially in the gut. 5-HT is a crucial enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. Gastroenteropathy is one of the most clinical problems in diabetic patients with frequent episodes of hyperglycemia. Changes in 5-HT expression may mediate gastrointestinal tract disturbances seen in diabetes, such as nausea and diarrhea. Based on the double immunohistochemical staining, this study determined the variability in the population of 5-HT-positive neurons in the porcine small intestinal enteric neurons in the course of streptozotocininduced diabetes. The results show changes in the number of 5-HT-positive neurons in the examined intestinal sections. The greatest changes were observed in the jejunum, particularly within the myenteric plexus. In the ileum, both de novo 5-HT synthesis in the inner submucosal plexus neurons and an increase in the number of neurons in the outer submucosal plexus were noted. The changes observed in the duodenum were also increasing in nature. The results of the current study confirm the previous observations concerning the involvement of 5-HT in inflammatory processes, and an increase in the number of 5-HT -positive neurons may also be a result of increased concentration of the 5-HT in the gastrointestinal tract wall and affects the motor and secretory processes, which are particularly intense in the small intestines.