Response Of Pigs Research Articles

The influence of long-lived radionuclides of Cesium - 137 and Strontium - 90 on some biochemical parameters of pig blood

The article presents the results of studying the effect of long-lived radionuclides 137Cs and 90Sr on some biochemical parameters of the blood serum of pigs. Ionizing radiation has a pronounced biological effect, and the radiobiological reaction in pigs begins with the formation of various kinds of cellular damage as a result of the transfer of radiation energy to them. A feature of the influence of incorporated irradiation on the body of pigs is not only decay, but also the formation of highly reactive ions and free radicals, which are involved in the primary radiation-chemical processes in organs and tissues with the formation of toxic metabolites. The severity of the damage depends on the type of radiation exposure, the power and dose of radiation, radiosensitivity and the age of a particular animal species. In addition, the tropism of long-lived radionuclides and the level of radioactive doses received for various organs and tissues of pigs are of particular importance.

The pig is a better model than the rabbit or rat for studying the pathophysiology of human mesenteric arteries.

Animal models are essential to investigate cardiovascular pathophysiology and pharmacology, but phylogenetic diversity makes it necessary to identify the model with vasculature most similar to that of humans. In this study, we compared the mesenteric arteries of humans, pigs, rabbits and rats in terms of the i) evolutionary changes in the amino acid sequences of α1 and β2 adrenoceptors; M1, M2, and M3 muscarinic receptors; and bradykinin (BKR) and thromboxane-prostanoid (TP) receptors, through bioinformatics tools; ii) expression of α1, β2, M1, M3 and TP receptors in each tunica, as assessed by immunofluorescence; and iii) reactivity to receptor-dependent and independent contractile agonists and relaxants, by performing organ bath assays. Phylogenetically, pigs showed the highest degree of evolutionary closeness to humans for all receptors, and with the exception of BKR, rabbits presented the greatest evolutionary difference compared to humans, pigs and rats. The expression of the measured receptors in the three vascular tunica in pigs was most similar to that in humans. Using a one-way ANOVA to determine the differences in vascular reactivity, we found that the reactivity of pigs was the most similar to that of humans in terms of sensitivity (pD2) and maximum effect of vascular reactivity (Emax) to KCl, phenylephrine, isoproterenol and carbachol. The pig is a better vascular model than the rabbit or rat to extrapolate results to human mesenteric arteries. Comparative vascular studies have implications for understanding the evolutionary history of different species. The presented findings are useful for identifying an animal model with a vasculature that is similar to that of humans. This information is important to extrapolate, with greater precision, the findings in arterial pathophysiology or pharmacology from animal models to the healthy or diseased human being.

A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor

A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans.

A Co-Culture Model of IPEC-J2 and Swine PBMC to Study the Responsiveness of Intestinal Epithelial Cells: The Regulatory Effect of Arginine Deprivation.

Simple SummaryThe interest in amino acids comes from their involvement in research on alternative strategies for the utilization of antibiotics on farms. Among several substances used to replace antibiotics, there is arginine, an essential amino acid in newborns and piglets. This amino acid has a protective role in intestinal immune cells and improves intestinal immunity. The purpose of this research was to define a co-culture model, in which intestinal epithelial cells can communicate with peripheral blood mononuclear cells (PBMC) to deepen the effects of arginine deprivation on intestinal epithelial cells over time. The main finding was that the lack of arginine highly impacts on intestinal and immune cells by way of immuno-regulation mediated by the expression of pro- and anti-inflammatory cytokines. The use of this experimental model could allow us to investigate the impact of and interactions between specific nutrients and the complex intestinal environment and, in addition, to assess feed additives to improve health and animal production.Arginine is a semi-essential amino acid, supplementation with which induces a reduction of intestinal damage and an improvement of intestinal immunity in weaned piglets, but the mechanism is not yet entirely clear. The aim of this study was to characterise a co-culture model by measuring changes in gene expression over time (24 and 48 h) in intestinal IPEC-J2 cells in the presence of immune cells activated with phytohemagglutinin and, consequently, to assess the effectiveness of arginine deprivation or supplementation in modulating the expression of certain cytokines related to the regulation of intestinal cells’ function. The main results show the crucial role of arginine in the viability/proliferation of intestinal cells evaluated by an MTT assay, and in the positive regulation of the expression of pro-inflammatory (TNF-α, IL-1α, IL-6, IL-8) and anti-inflammatory (TGF-β) cytokines. This experimental model could be important for analysing and clarifying the role of nutritional conditions in intestinal immune cells’ functionality and reactivity in pigs as well as the mechanisms of the intestinal defence system. Among the potential applications of our in vitro model of interaction between IEC and the immune system there is the possibility of studying the effect of feed additives to improve animal health and production.

The relationship between acrosome reaction and polyunsaturated fatty acid composition in boar sperm.

This study investigated the relationship between acrosome reactions and fatty acid composition with respect to fertility in boar sperm. The acrosome reaction was induced more than 85% by 60mM methyl-beta-cyclodextrin (MBCD), and plasma membrane integrity was significantly reduced dependent on the MBCD level in boar sperm (p<.05). The acrosome-reacted sperm exhibited significantly higher saturated fatty acids (SFAs) and lower polyunsaturated fatty acids (PUFAs) composition compared to the non-acrosome reaction group (p<.0001). In addition, the PUFAs, C22:5n-6 (docosapentaenoic acid [DPA]; p<.01) and C22:6n-3 (docosahexaenoic acid [DHA]; p<.0001) were significantly decreased, and cleavage and blastocyst formation of oocytes were significantly (p<.0001) decreased in acrosome-reacted sperm relative to non-acrosome-reacted sperm. Moreover, acrosome reaction was positively correlated with SFAs, whereas negatively correlated with PUFAs, of the PUFAs, the DPA (p=.0005) and DHA (p=<.0001) were negatively correlated with the acrosome reaction. Therefore, these results suggest that the PUFAs composition of sperm is closely involved in acrosome reaction in pigs.

Visual laterality in pigs: monocular viewing influences emotional reactions in pigs

Understanding animal emotions is an important scientific and ethical question but assessing emotional valence is still considered challenging. As the observation of lateralization (hemispheric asymmetries in structure and/or function) can provide insight into the underlying processes of the cognitive, physiological and behavioural components of emotions, it is a promising approach for studying them. The emotional valence hypothesis states that positive emotions are mostly processed by the left hemisphere, while negative emotions are mostly processed by the right hemisphere. Support for this hypothesis is still not conclusive; therefore, our study tested it in the context of visual laterality for viewing positive or negative emotionally conditioned stimuli. Ninety male piglets were either positively (food-reward) or negatively (mild punishment) conditioned to an object. Afterwards, the object was presented without the reinforcer under three different treatments: patch on the left or right eye (reducing input to the contralateral hemisphere) or patch between the eyes (the control). Monocular viewing had no clear effects on the negatively conditioned subjects. In contrast, in the positively conditioned group, covering the right eye caused a longer interruption of vocalization, a longer latency to touch the object, a shorter duration of exploring the arena and an increased vagal activity compared to the control. This suggests that reduced processing in the left hemisphere leads to heightened attention that is accompanied by a general orienting response, possibly resulting from a reduced positive appraisal. These findings therefore partially support the emotional valence hypothesis and suggest an important role of the left hemisphere in the quick recognition of a positive stimulus. This study demonstrated that investigating the lateralized processing of emotions can provide insight into the mechanisms of positive appraisal in animals.

Dynamics of morphological and biochemical indicators of blood of sucking piglets at different levels of iodine citrate in sows rations

The article presents the results of experimental studies on the determination of the influence of iodine citrate on hematological and biochemical parameters of blood of sucking piglets. It was established that hemopoiesis and metabolic reactions in pigs depend on the level of Iodine in the sows, and in the later period (the 10th day) and from the receipt of the biometal as part of the prestarter. Iodine, in nanocitate form, at the expense of high bioavailability and chemical activity, provided the need for thyroid gland in it in much less quantities than the amounts recommended for pregnant and lactating sows in the form of potassium iodide. It has been established that at the admission to the body of a sow 0.095–0.19 mg/kg of feeding of iodine in a nanocyte form (1/4–1/2 of the recommended amount of iodine in the form of CI), its positive effect on hemopoiesis and metabolic processes in newborn piglets is peculiar (increased number of red blood cells, hemoglobin content, high percentage of lymphocytes, increases in the concentration of total protein and in particular albumin, against the backdrop of growth in blood plasma levels of CSF, the concentration of hormones T3 and T4 is quite stable. A higher dose in the premix of iodine citrate (1 : 1) is irrational and most likely undesirable, since against the background of inhibition of this group of erythropoiesis, eosinophilia and lymphopenia, the protein synthesis function decreases and the activity of AlAT, AsAT increases. Hematological and biochemical parameters of blood of piglets obtained from sows, which received a minimum amount of iodine in the form of citrate (0.1 : 1) with premix, did not undergo significant changes, were within the limits of physiological values, although in comparison with the animals of the control group, and particularly, the piglets of the group D2 and D3 tended to decrease (growth). Consequently, iodine citrate as a source of iodine for pregnant and subsistence sows can be recommended in the amounts: 0.095–0.19 mg/kg and 0.125–0.25 mg/kg feed.

Diurnal variations in methionine content and expression of certain genes involved in DNA methylation reaction in pigs

Whether methionine content and its metabolites in liver and skeletal muscle show diurnal rhythmicity remains unknown. In the present study, we investigated the diurnal rhythms in methionine and S-adenosylmethionine (SAM) in plasma, liver, and longissimus thoracis muscle, as well as in enzymes involved in methionine-related transmethylation reaction using pigs maintained in a 12-h photoperiod. The results showed that concentration of methionine and SAM, as well as mRNA expression of methionine adenosyltransferase (MAT1A), DNA methyltranferase (DNMT3A and DNMT3B) in liver showed diurnal rhythmicity. Comparison with typical circadian clock genes revealed a similarity between the diurnal patterns of MAT1A and cryptochrome circadian clock 1 (CRY1) expression, whereas the daily patterns of MAT2A, DNMT3A, and DNMT3B expression were reversely related to the expression patterns of Timeless. These results imply that much attention should be paid to rhythms of methionine metabolism and methylation activity in the pathogenesis of diseases, such as cancer and metabolic syndrome.

Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement?

A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead® carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals. Based on overwhelming evidence of a role of anaphylatoxins in hypersensitivity reactions, the need to further explore the role of C activation in the reported and other reactions is highlighted. C-activation-related and C-independent pseudoallergies (CARPA and CIPA) can proceed simultaneously, as outlined by the 'double-hit' hypothesis.

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes.

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

Dietary tryptophan supplementation and affective state in pigs

Abstract The assessment and provision of welfare in farm animals has become a major issue in animal science. A key element for providing good welfare is the enabling of positive affective states in the animals. As the serotonergic system plays a central role in regulating affective behavior, an increase in centrally available serotonin (5-HT) via dietary supplementation of its precursor, tryptophan (TRP), might be an approach to induce positive affective states. Therefore, the aim of our study was to investigate the effects of dietary TRP supplementation on brain TRP metabolism and 5-HT levels but also on affective state and behavioral reactivity in pigs. All subjects were fed a standard diet until 8 weeks of age, then feed was changed for all animals, with half the animals (control) receiving a diet with the recommended TRP content (2.5 g/kg), whereas the other half (TRP+) received a TRP-enriched diet (10.2 g/kg). In part 1 of our study, we investigated the effects of the dietary TRP supplementation on TRP metabolism in brain areas related to affective and cognitive processing. We found significantly increased concentrations of TRP and its metabolites in nearly all analyzed brain tissues. In part 2 of our study, we analyzed the effects of these alterations on the affective state as measured in a cognitive bias test, namely the spatial judgment task, but also on behavioral reactivity as measured in a combined open field/novel object test. The TRP enrichment revealed no significant behavioral changes in the open field/novel object tests. In the spatial judgment task, the TRP+ group showed more pessimistic behavior after dietary change than before. Thus, our results do not support the suggestion that TRP supplementation induces positive affective states and thus improves animal welfare in pigs.

Does heat stress alter the pig's response to dietary fat?

Heat stress (HS) results in major losses to the pork industry via reduced growth performance and, possibly, carcass fat quality. The experimental objective was to measure the effects of HS on the pig's response to dietary fat in terms of lipid digestion, metabolism, and deposition over a 35-d finishing period. A total of 96 PIC 337 × C22/C29 (PIC, Inc., Hendersonville, TN) barrows (initial BW of 100.4 ± 1.2 kg) were randomly allotted to 1 of 9 treatments arranged as a 3 × 3 factorial: thermoneutral (TN; constant 24°C; ad libitum access to feed), pair-fed thermoneutral (PFTN; constant 24°C; limit fed based on previous HS daily feed intake), or HS (cyclical 28°C nighttime, 33°C from d 0 to 7, 33.5°C from d 7 to 14, 34°C from d 14 to 21, 34.5°C from d 21 to 28, and 35°C from d 28 to 35 daytime; ab libitum access to feed) and diet (a corn-soybean meal-based diet with 0% added fat [CNTR], CNTR with 3% added tallow [TAL; iodine value {IV} = 41.8], or CNTR with 3% added corn oil [CO; IV = 123.0]). No interactions between environment and diet were evident for any major response criteria ( ≥ 0.063). Rectal temperature increased due to HS (39.0°C for HS, 38.1°C for TN, and 38.2°C for PFTN; < 0.001). Heat stress decreased ADFI (27.8%; < 0.001), ADG (0.72 kg/d for HS, 1.03 kg/d for TN, and 0.78 kg/d for PFTN; < 0.001), and G:F (0.290 for HS, 0.301 for TN, and 0.319 for PFTN; = 0.006). Heat stress barrows required 1.2 Mcal of ME intake more per kilogram of BW gain than PFTN ( < 0.001). Heat stress tended to result in the lowest apparent total tract digestibility of acid hydrolyzed ether extract (AEE; 59.0% for HS, 60.2% for TN, and 61.4% for PFTN; = 0.055). True total tract digestibility (TTTD) of AEE of CO-based diets (99.3%) was greater than that of CNTR (97.3%) and TAL-based diets (96.3%; = 0.012). Environment had no impact on TTTD of AEE ( = 0.118). Environment had no impact on jowl IV at market (69.2 g/100 g for HS, 69.3 g/100 g for TN, and 69.8 g/100 g for PFTN; = 0.624). Jowl IV at market increased with increasing degree of unsaturation of the dietary fat (68.5 g/100 g for CNTR, 68.2 g/100 g for TAL, and 71.5 g/100 g for CO; < 0.001). Heat stress decreased mRNA abundance of and ( ≤ 0.041). Heat stress and CO increased mRNA abundance of ( ≤ 0.047), and CO increased abundance of ( = 0.011). In conclusion, HS does not alter the pig's response to dietary fat. However, HS leads to reduced ADG, ADFI, G:F, and caloric efficiency and a suppression of mRNA abundance of genes involved in the lipolytic cascade, which resulted in a phenotype that was fatter than PFTN.

Liposome‐Supported Peritoneal Dialysis for the Treatment of Hyperammonemia‐Associated Encephalopathy

Hyperammonemia can lead to cerebral dysfunction, encephalopathy, coma, and death if not treated adequately. The poor prognosis associated with this condition reflects the unmet medical need for effective ammonia‐lowering treatments. Here, the translational potential of liposome‐supported peritoneal dialysis (LSPD), a recently‐developed detoxification strategy for the removal of small ionizable molecules like ammonia, is described. Dialysis fluids supplemented with micrometer‐sized, transmembrane pH‐gradient liposomes are prepared via an innovative, osmotic shock‐based method overcoming sterilization and long‐term stability issues. LSPD is able to sequester ammonia in healthy rats in relation to the injected dose, buffering capacity of the liposomal core, and membrane composition. In a rat model of cirrhosis, LSPD outperforms conventional peritoneal dialysis in lowering plasmatic ammonia levels and attenuating brain edema. LSPD does not trigger any hypersensitive reaction in pigs, a side effect commonly observed upon the injection of colloids in this animal model and in humans. These findings support the development of LSPD for the treatment of hyperammonemia‐induced encephalopathy.

Response of Selenium and Selenogenome in Immune Tissues to LPS-Induced Inflammatory Reactions in Pigs.

Circulating concentration of the essential trace element selenium (Se) was significantly lower in inflammatory disorders. Although Se plays physiological roles mainly through the function of 25 selenoproteins, the response of the selenogenome in immune tissues during inflammatory reactions remains unclear. The objective of this study was to determine the Se retention and selenogenome expression in immune tissues during the lipopolysaccharide (LPS)-induced inflammatory response in porcine. A total of 12 male pigs were randomly divided into two groups and injected with LPS or saline. After 4h postinjection, blood samples were collected and pigs were euthanized. Pigs challenged with LPS had 36.8 and 16.6% lower (P<0.05) Se concentrations in the serum and spleen, respectively, than those injected with saline. Moreover, the activities of GPX decreased (P<0.05) by 23.4, 26.6, and 30.4% in the serum, thymus, and lymph node, respectively, in the pigs injected with LPS. Furthermore, the LPS challenge altered (P<0.05) the mRNA expression of 14, 16, 10, and 6 selenoprotein genes in the liver, spleen, thymus, and lymph node, respectively. Along with 10 previously reported selenoprotein genes, the response of Txnrd2, Txnrd3, Sep15, Selh, Seli, Seln, Selo, Selt, Selx, and Sephs2 to inflammatory reaction in immune tissues were newly illustrated in this study. In conclusion, the LPS-induced inflammatory response impaired Se metabolism and was associated with dysregulation of the selenogenome expression in immune tissues.

Effect of handling on neurotransmitter profile in pig brain according to fear related behaviour

Chemical neurotransmitters (NT) are principal actors in all neuronal networks of animals. The central nervous system plays an important role in stress susceptibility and organizes the response to a stressful situation through the interaction of the dopaminergic and the serotonergic pathways, leading to the activation of the hypothalamus-pituitary-adrenal axis (HPA). This study was designed to investigate: a) the effects of stressful handling of pigs at the slaughterhouse on the neurotransmitter profile in four brain areas: amygdala, prefrontal cortex (PFC), hippocampus and hypothalamus, and b) whether the alterations in the brain NT profile after stressful handling were associated with fear, determined by the tonic immobility (TI) test. In the first place, the characterization of the NT profile allowed to distinguish the four brain areas in a principal component analysis. The most crucial pathway involved in the reaction of pigs to a stressful handling was the serotonergic system, and changes were observed in the amygdala with a decrease in serotonin (5-HT) and total indoleamines, and in the hippocampus, where this pathway was activated. Fearful and non-fearful pigs did not show significant differences in their NT profile in control conditions, but when subjected to a stressful handling in the slaughterhouse, fearful animals showed a significant variation in the serotonin pathway and, in a lesser extent, the dopamine (DA) pathway. In conclusion, the existence of an underlying biological trait - possibly fearfulness - may be involved in the pig's response toward stressful challenges, and the serotonergic system seems to play a central role in this response.

305 Does heat stress alter the pig's response to dietary fat source, as it relates to apparent or true total tract digestibility of dietary lipids?

305 Does heat stress alter the pig's response to dietary fat source, as it relates to apparent or true total tract digestibility of dietary lipids?

An experimental study with a vaccine strain of porcine reproductive and respiratory syndrome virus to determine effects on viremia assessed by reverse transcriptase-polymerase chain reaction in pigs fed rations medicated with tilmicosin or non-medicated

Objectives: To determine if feed medicated with tilmicosin affects viremia (assessed using reverse transcriptase-polymerase chain reaction [RT-PCR]) in pigs exposed to a vaccine strain of porcine reproductive and respiratory syndrome virus (PRRSV), clinical signs associated with vaccination (body temperature), and average daily gain. Materials and methods: Purebred Yorkshire pigs (N = 192) were each assigned to one of five treatment groups. Groups 1a and 1b remained PRRSV-negative (controls), while Groups 2, 3, and 4 were injected with a modified-live (MLV) PRRSV vaccine. Groups 1b and 2 were fed non-medicated feed. Rations contained tilmicosin at 400 mg per kg for Group 1a and Group 4 and 200 mg per kg for Group 3. Blood samples were collected to measure serum tilmicosin concentrations and assess PRRSV viremia. Bronchoalveolar lavage was performed and macrophages assessed for PRRSV viremia and tilmicosin concentrations. Results: Groups 1a and 1b remained PRRSV-negative. Number of PRRSV copies per mL in serum was highest in inoculated pigs at 10 days post inoculation, but did not differ among the three inoculated groups. Average daily gain (ADG) was higher in groups fed rations containing 400 mg per kg tilmicosin than in groups on non-medicated rations. Clinical signs of disease were absent in all pigs. Implications: Viremia associated with an MLV vaccine strain of PRRSV does not differ between pigs fed rations containing 200 or 400 mg per kg of tilmicosin. In the absence of clinical disease, pigs consuming tilmicosin-medicated feed have higher ADG than pigs consuming non-medicated feed.

Third-stage nematode larvae of Contracaecum osculatum from Baltic cod (Gadus morhua) elicit eosinophilic granulomatous reactions when penetrating the stomach mucosa of pigs.

Third-stage larvae of the anisakid nematode Contracaecum osculatum were recovered from livers of Atlantic cod (Gadus morhua) caught in the Baltic Sea (June 2014) and used for experimental infection of two pigs (one male and one female). Each pig received 215 larvae by oral infection (feeding with minced cod liver containing live nematode larvae). Pigs were euthanized after 5 days, necropsied, and subjected to parasitological investigation. A total of 12 larvae were found penetrating the mucosa of the ventricle (7 in the female pig and 5 in the male pig) eliciting a granulomatous reaction at the penetration site. Four non-attached larvae were found in the female pig stomach and one in the male pig. Petechial bleeding was observed at several locations in the ventricular mucosa where larvae were located. Histological examination of the stomach mucosa revealed a massive cellular infiltration (giant cells, lymphocytes, macrophages, granulocytes, and fibroblast like cells) around the penetrating larva. Mononuclear and polymorphonuclear cells containing eosinophilic granulae were particularly prominent in the granulomas. Reactions correspond to reactions in pigs following experimental infection with the human pathogenic anisakid larvae Anisakis sp. and Pseudoterranova sp. which suggests that C. osculatum might have a zoonotic potential as well.

Features of complement activation-related pseudoallergy to liposomes with different surface charge and PEGylation: Comparison of the porcine and rat responses

Pigs are known to provide a sensitive model for studying complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction to liposomal and many other nanomedicines that limits their clinical use. The utility of rats as a CARPA model has, however, not been analyzed to date in detail. The present study compared the two models by inducing CARPA with i.v. bolus injections of two reactogenic liposomes that differed from each other in surface properties: one was AmBisome, a strong anionic, free-surface small unilamellar liposome (SUV), while the other was neutral, polyethylene glycol (PEG)-grafted SUV wherein the 2kDa-PEG was anchored to the membrane via cholesterol (Chol-PEG). Both in pigs and rats AmBisome caused significant consumption of C3, indicating C activation, along with paralleling massive changes in blood pressure, white blood cell, platelet counts and in plasma thromboxane B2 levels, indicating CARPA. These processes were similar in the two species in terms of kinetics, but significantly differed in the doses that caused major hemodynamic changes (~0.01 and ~22mg phospholipid (PL)/kg in pigs and rats, respectively). Pigs responded to AmBisome with pulmonary hypertension and systemic hypotension, and the reaction was not tachyphylactic. The major response of rats was systemic hypotension, leukopenia followed by leukocytosis, and thrombocytopenia. Chol-PEG liposomes caused severe reaction in pigs at 0.1mg/kg, while the reaction they caused in rats was mild even at 300mgPL/kg. Importantly, the reaction to Chol-PEG in pigs was partly tachyphylactic. These observations highlight fundamental differences in the immune mechanisms of porcine and rat CARPA, and also show a major impact of liposome surface characteristics, determining the presence or absence of tachyphylaxis. The data suggest that rats are 2–3 orders of magnitude less sensitive to liposomal CARPA than pigs; however, the causes of these differences, the PEG-dependent tachyphylaxis and the massive reactivity of Chol-PEG liposomes remain unclear.

Restricting sulfur amino acid intake in growing pigs challenged with lipopolysaccharides decreases plasma protein and albumin synthesis

Litvak, N., Htoo, J. K. and de Lange, C. F. M. 2013. Restricting sulfur amino acid intake in growing pigs challenged with lipopolysaccharides decreases plasma protein and albumin synthesis. Can. J. Anim. Sci. 93: 505–515. Chronic subclinical levels of disease occur frequently in swine production and compromise nutrient utilization efficiency. Methionine and cysteine (M+C) are involved in the pig's response to immune system stimulation (ISS), acting as substrates for the synthesis of compounds involved in the immune response, such as acute phase proteins (APP). This study was conducted to determine the impact of ISS with lipopolysaccharide (LPS) and M+C intake (high vs. low; 4.0 vs. 2.2 g d−1) on the fractional synthesis rate (FSR) of plasma albumin and fibrinogen, as well as protein in plasma and various tissues of starter pigs. Fifteen pigs (9.8±1.4 kg body weight) were allotted to one of three treatments: (1) Control (LPS− and high M+C), (2) LPS+ and high M+C, or (3) LPS+ and low M+C. Pigs were given intramuscular injections of increasing doses of LPS 1 and 3 d before determining FSR using an intravenous infusion of a flooding dose of L-[ring−1H5]-phenylalanine. Plasma levels of APP were not affected by the LPS challenge (P&gt;0.10); only plasma albumin levels decreased with reduced M+C intake (P=0.02). Total plasma protein FSR was increased during the LPS challenge (50.3 vs. 56.9% d−1, SEM = 1.6; P=0.01). Albumin FSR was not affected by an LPS challenge (P&gt;0.10), but decreased with reduced M+C intake during the LPS challenge (49.5 vs. 41.9% d−1, SEM = 1.6; P=0.005). Spleen protein FSR tended to increase during the LPS challenge (P=0.08). There were no treatment effects on protein FSR in liver, small intestine, loin or plasma fibrinogen (P&gt;0.10). Restricting M+C intake during a LPS challenge decreases albumin synthesis and tends to reduce plasma protein synthesis, implicating M+C as important nutrients involved in the immune response.