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Sample records for chronic porcine model

  1. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

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    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  2. A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease

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    Giuseppe Biondi-Zoccai

    2013-01-01

    Full Text Available Cardiac pathologies are among the leading causes of mortality and morbidity in industrialized countries, with myocardial infarction (MI representing one of the major conditions leading to heart failure (HF. Hitherto, the development of consistent, stable, and reproducible models of closed-chest MI in large animals, meeting the clinical realism of a patient with HF subsequent to chronic ischemic necrosis, has not been successful. We hereby report the design and ensuing application of a novel porcine experimental model of closed-chest chronic ischemia suitable for biomedical research, mimicking post-MI HF. We also emphasize the key procedural steps involved in replicating this unprecedented model, from femoral artery and vein catheterization to MI induction by permanent occlusion of the left anterior descending coronary artery through superselective deployment of platinum-nylon coils, as well as endomyocardial biopsy sampling for histologic analysis and cell harvesting. Our model could indeed represent a valuable contribution and tool for translational research, providing precious insights to understand and overcome the many hurdles concerning, and currently quenching, the preclinical steps mandatory for the clinical translation of new cardiovascular technologies for personalized HF treatments.

  3. Enhanced Myocardial Vascularity and Contractility by Novel FGF-1 Transgene in a Porcine Model of Chronic Coronary Occlusion

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    Janet L. Parker

    2008-12-01

    Full Text Available Background: Angiogenesis gene therapy has long been sought as a novel alternative treatment for restoring the blood flow and improving the contractile function of the ischemic heart in selected clinical settings. Angiogenic fibroblast growth factor-1 (FGF-1 is a promising candidate for developing a promising gene therapy protocol due to its multipotent ability to stimulate endothelial cell (EC growth, migration, and tube formation. Despite these advantages, however, FGF gene therapy has suffered setbacks mainly due to the inefficient delivery rate of the growth factor in vivo. Given the potent angiogenic effect of FGF-1, we reasoned that constitutively synthesized minute quantities of this polypeptide hormone, when empowered with the ability to escape the cellular constraint, could freely act in a paracrine/autocrine fashion on nearby existing capillary plexuses and lead to neovascularization and restoration of the blood flow to ischemic tissues for reparative purpose. Methods: We report the direct gene transfer of a retroviral-based mammalian expression vector encoding a secreted form of FGF-1 (sp-FGF-1 for the purpose of therapeutic angiogenesis into the porcine myocardium subjected to the surgical placement of an ameroid occluder to induce the chronic coronary occlusion of the left circumflex coronary artery (LCx and regional myocardial ischemia. Coronary angiography, performed 3 weeks after surgery, confirmed the interruption of the blood flow in the LCx distal to the site of ameroid placement. Results: Immunohistochemical analysis using antibody specific to von Willebrand factor (vWF, an endothelial marker, showed a significant increase (p<0.05 in myocardial vascularity in the sp-FGF-1 hearts compared to the control (vector alone. Importantly, an assessment of the cardiac function by echocardiography, performed 3 weeks after surgery, demonstrated improved cardiac contractility due to increased left ventricular free wall contraction in the

  4. Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial.

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    Sanne J Jansen of Lorkeers

    Full Text Available Recently cardiomyocyte progenitor cells (CMPCs were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls.Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes.We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA. Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals.Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction.

  5. Porcine models of muscular dystrophy.

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    Selsby, Joshua T; Ross, Jason W; Nonneman, Dan; Hollinger, Katrin

    2015-01-01

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease.

  6. A porcine model for teaching surgical cricothyridootomy

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    Fernando Antonio Campelo Spencer Netto

    2015-06-01

    Full Text Available OBJECTIVE: To evaluate the acceptability of an educational project using A porcine model of airway for teaching surgical cricothyroidotomy to medical students and medical residents at a university hospital in southern Brazil.METHODS: we developed a teaching project using a porcine model for training in surgical cricothyroidotomy. Medical students and residents received lectures about this surgical technique and then held practical training with the model. After the procedure, all participants filled out a form about the importance of training in airway handling and the model used.RESULTS: There were 63 participants. The overall quality of the porcine model was estimated at 8.8, while the anatomical correlation between the model and the human anatomy received a mean score of 8.5. The model was unanimously approved and considered useful in teaching the procedure.CONCLUSION: the training of surgical cricothyroidotomy with a porcine model showed good acceptance among medical students and residents of this institution.

  7. Porcine model of hemophilia A.

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    Kashiwakura, Yuji; Mimuro, Jun; Onishi, Akira; Iwamoto, Masaki; Madoiwa, Seiji; Fuchimoto, Daiichiro; Suzuki, Shunichi; Suzuki, Misae; Sembon, Shoichiro; Ishiwata, Akira; Yasumoto, Atsushi; Sakata, Asuka; Ohmori, Tsukasa; Hashimoto, Michiko; Yazaki, Satoko; Sakata, Yoichi

    2012-01-01

    Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8). Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.

  8. Porcine model of hemophilia A.

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    Yuji Kashiwakura

    Full Text Available Hemophilia A is a common X chromosome-linked genetic bleeding disorder caused by abnormalities in the coagulation factor VIII gene (F8. Hemophilia A patients suffer from a bleeding diathesis, such as life-threatening bleeding in the brain and harmful bleeding in joints and muscles. Because it could potentially be cured by gene therapy, subhuman animal models have been sought. Current mouse hemophilia A models generated by gene targeting of the F8 have difficulties to extrapolate human disease due to differences in the coagulation and immune systems between mice and humans. Here, we generated a porcine model of hemophilia A by nuclear transfer cloning from F8-targeted fibroblasts. The hemophilia A pigs showed a severe bleeding tendency upon birth, similar to human severe hemophiliacs, but in contrast to hemophilia A mice which rarely bleed under standard breed conditions. Infusion of human factor VIII was effective in stopping bleeding and reducing the bleeding frequency of a hemophilia A piglet but was blocked by the inhibitor against human factor VIII. These data suggest that the hemophilia A pig is a severe hemophilia A animal model for studying not only hemophilia A gene therapy but also the next generation recombinant coagulation factors, such as recombinant factor VIII variants with a slower clearance rate.

  9. Porcine models of muscular dystrophy

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    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

  10. A porcine model of progressive Parkinson disease established by chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication

    DEFF Research Database (Denmark)

    Nielsen, M S; Glud, Andreas Nørgaard; Møller, Arne

    2009-01-01

    not imitate the progression of PD well enough. To address this, we have established a progressive PD model on Göttingen minipigs based on chronic infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Fourteen female Göttingen minipigs were implanted subcutaneously with infusion pumps......, whereas animals receiving 24 mg/day had their pumps turned off after 11 days due to severe PD symptoms. Histopathological examination showed increased nigral neuron loss with increased MPTP dosages. HPLC showed decreased striatal dopamine levels at daily MPTP dosages of 12 mg or higher. Stereological...

  11. A porcine model of haematogenous brain infectionwith staphylococcus aureus

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    Astrup, Lærke Boye; Agerholm, Jørgen Steen; Nielsen, Ole Lerberg;

    2012-01-01

    A PORCINE MODEL OF HAEMATOGENOUS BRAIN INFECTION WITH STAPHYLOCOCCUS AUREUS Astrup Lærke1, Agerholm Jørgen1, Nielsen Ole1, Jensen Henrik1, Leifsson Páll1, Iburg Tine2. 1: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark boye@life.ku.dk 2: National Veterinary Institute......, Uppsala, Sweden Introduction Staphylococcus aureus (S.aureus) is a common cause of sepsis and brain abscesses in man and a frequent cause of porcine pyaemia. Here we present a porcine model of haematogenous S. aureus-induced brain infection. Materials and Methods Four pigs had two intravenous catheters...

  12. Development of left ventricular hypertrophy in a novel porcine model of mitral regurgitation

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    Ravn, Nathja; Zois, Nora Elisabeth; Moesgaard, Sophia Gry

    2014-01-01

    OBJECTIVES: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy. DESIGN: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular...... traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included. Echocardiographic LV size and heart weight assessed at euthanasia were used to evaluate the development of LV enlargement and eccentric hypertrophy after 8 weeks follow-up. RESULTS: Eight...... for chronic moderate to severe nonischemic MR with development of LV enlargement and eccentric hypertrophy within 8 weeks has been established in pigs....

  13. Structure and Function of a Nonruminant Gut: A Porcine Model

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    Tajima, Kiyoshi; Aminov, Rustam

    2015-01-01

    In many aspects, the anatomical, physiological, and microbial diversity features of the ruminant gut are different from that of the monogastric animals. Thus, the main aim of this chapter is to give a comparative overview of the structure and function of the gastrointestinal tract of a nonruminant...... monogastric animal, and here it is represented by a pig model. In this chapter, we describe and discuss (i) microbial diversity in different parts of the porcine gut; (ii) differences between the ruminant and nonruminant gut; (iii) main events during colonization and succession of microbiota in the porcine...... gut; (iv) effects of various feed additives including antibiotics, phages, probiotics, and prebiotics on pigs; and (v) the use of the porcine model in translational medicine....

  14. Functional Characterization of a Porcine Emphysema Model

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    Bruun, Camilla Sichlau; Jensen, Louise Kruse; Leifsson, Páll Skuli

    2013-01-01

    Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenoty......).The pig model is comparable to human emphysema patients and the ITGB6−/− mouse model with respect to both morphology and functionality....... develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression.A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6−/− mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined...

  15. Experimental porcine model of complex fistula-in-ano

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    A Ba-Bai-Ke-Re, Ma-Mu-Ti-Jiang; Chen, Hui; Liu, Xue; Wang, Yun-Hai

    2017-01-01

    AIM To establish and evaluate an experimental porcine model of fistula-in-ano. METHODS Twelve healthy pigs were randomly divided into two groups. Under general anesthesia, the experimental group underwent rubber band ligation surgery, and the control group underwent an artificial damage technique. Clinical magnetic resonance imaging (MRI) and histopathological evaluation were performed on the 38th d and 48th d after surgery in both groups, respectively. RESULTS There were no significant differences between the experimental group and the control group in general characteristics such as body weight, gender, and the number of fistula (P > 0.05). In the experimental group, 15 fistulas were confirmed clinically, 13 complex fistulas were confirmed by MRI, and 11 complex fistulas were confirmed by histopathology. The success rate in the porcine complex fistula model establishment was 83.33%. Among the 18 fistulas in the control group, 5 fistulas were confirmed clinically, 4 complex fistulas were confirmed by MRI, and 3 fistulas were confirmed by histopathology. The success rate in the porcine fistula model establishment was 27.78%. Thus, the success rate of the rubber band ligation group was significantly higher than the control group (P < 0.05). CONCLUSION Rubber band ligation is a stable and reliable method to establish complex fistula-in-ano models. Large animal models of complex anal fistulas can be used for the diagnosis and treatment of anal fistulas. PMID:28348488

  16. Prevention of primary vascular graft infection with silver-coated polyester graft in a porcine model

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    Gao, H; Sandermann, J; Prag, J;

    2010-01-01

    To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model.......To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model....

  17. Transorbital target localization in the porcine model

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    DeLisi, Michael P.; Mawn, Louise A.; Galloway, Robert L.

    2013-03-01

    Current pharmacological therapies for the treatment of chronic optic neuropathies such as glaucoma are often inadequate due to their inability to directly affect the optic nerve and prevent neuron death. While drugs that target the neurons have been developed, existing methods of administration are not capable of delivering an effective dose of medication along the entire length of the nerve. We have developed an image-guided system that utilizes a magnetically tracked flexible endoscope to navigate to the back of the eye and administer therapy directly to the optic nerve. We demonstrate the capabilities of this system with a series of targeted surgical interventions in the orbits of live pigs. Target objects consisted of NMR microspherical bulbs with a volume of 18 μL filled with either water or diluted gadolinium-based contrast, and prepared with either the presence or absence of a visible coloring agent. A total of 6 pigs were placed under general anesthesia and two microspheres of differing color and contrast content were blindly implanted in the fat tissue of each orbit. The pigs were scanned with T1-weighted MRI, image volumes were registered, and the microsphere containing gadolinium contrast was designated as the target. The surgeon was required to navigate the flexible endoscope to the target and identify it by color. For the last three pigs, a 2D/3D registration was performed such that the target's coordinates in the image volume was noted and its location on the video stream was displayed with a crosshair to aid in navigation. The surgeon was able to correctly identify the target by color, with an average intervention time of 20 minutes for the first three pigs and 3 minutes for the last three.

  18. Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview.

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    Litten-Brown, J C; Corson, A M; Clarke, L

    2010-06-01

    The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to

  19. Creating Porcine Biomedical Models Through Recombineering

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    Lawrence B. Schook

    2006-03-01

    Full Text Available Recent advances in genomics provide genetic information from humans and other mammals (mouse, rat, dog and primates traditionally used as models as well as new candidates (pigs and cattle. In addition, linked enabling technologies, such as transgenesis and animal cloning, provide innovative ways to design and perform experiments to dissect complex biological systems. Exploitation of genomic information overcomes the traditional need to choose naturally occurring models. Thus, investigators can utilize emerging genomic knowledge and tools to create relevant animal models. This approach is referred to as reverse genetics. In contrast to ‘forward genetics’, in which gene(s responsible for a particular phenotype are identified by positional cloning (phenotype to genotype, the ‘reverse genetics’ approach determines the function of a gene and predicts the phenotype of a cell, tissue, or organism (genotype to phenotype. The convergence of classical and reverse genetics, along with genomics, provides a working definition of a ‘genetic model’ organism (3. The recent construction of phenotypic maps defining quantitative trait loci (QTL in various domesticated species provides insights into how allelic variations contribute to phenotypic diversity. Targeted chromosomal regions are characterized by the construction of bacterial artificial chromosome (BAC contigs to isolate and characterize genes contributing towards phenotypic variation. Recombineering provides a powerful methodology to harvest genetic information responsible for phenotype. Linking recombineering with gene-targeted homologous recombination, coupled with nuclear transfer (NT technology can provide ‘clones’ of genetically modified animals.

  20. Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2014-09-01

    The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.

  1. Porcine Model In The Laparoscopic Liver Surgery Training

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    Komorowski Andrzej L.

    2015-08-01

    Full Text Available The aim of the study was to evaluate the possibility to use live anesthetized pigs as a model for laparoscopic liver resection. During two days laparoscopy course two trainees were operating on two live animals performing exposure of the liver, Pringle manoeuver, division of liver ligaments, dissecting of the structures inside the hepatoduodenal ligament, dissection of the hepatic veins and left lateral liver sectionectomy. Exposure of the liver and Pringle manoeuver were performed correctly within 50 and 35 minutes. Left lateral sectionectomy has been performed correctly within 2 hours. The full dissection of the hepatoduodenal ligament and exposure of the hepatic veins were judged as insufficient by experienced laparoscopic tutors. There was one injury to the suprahepatic vena cava that was managed laparoscopically. The porcine model can be used as an advanced training for laparoscopic liver surgery.

  2. In vivo response to an implanted shape memory polyurethane foam in a porcine aneurysm model.

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    Rodriguez, Jennifer N; Clubb, Fred J; Wilson, Thomas S; Miller, Matthew W; Fossum, Theresa W; Hartman, Jonathan; Tuzun, Egemen; Singhal, Pooja; Maitland, Duncan J

    2014-05-01

    Cerebral aneurysms treated by traditional endovascular methods using platinum coils have a tendency to be unstable, either due to chronic inflammation, compaction of coils, or growth of the aneurysm. We propose to use alternate filling methods for the treatment of intracranial aneurysms using polyurethane-based shape memory polymer (SMP) foams. SMP polyurethane foams were surgically implanted in a porcine aneurysm model to determine biocompatibility, localized thrombogenicity, and their ability to serve as a stable filler material within an aneurysm. The degree of healing was evaluated via gross observation, histopathology, and low vacuum scanning electron microscopy imaging after 0, 30, and 90 days. Clotting was initiated within the SMP foam at time 0 (<1 h exposure to blood before euthanization), partial healing was observed at 30 days, and almost complete healing had occurred at 90 days in vivo, with minimal inflammatory response.

  3. Cardiac dysfunction in a porcine model of pediatric malnutrition

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Lykke, Mikkel; Nielsen, Anne-Louise Hother;

    2015-01-01

    and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet......BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased...

  4. Emerging technologies to create inducible and genetically defined porcine cancer models

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    Lawrence B Schook

    2016-02-01

    Full Text Available There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

  5. Characterization of porcine skin as a model for human skin studies using infrared spectroscopic imaging.

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    Kong, Rong; Bhargava, Rohit

    2011-06-07

    Porcine skin is often considered a substitute for human skin based on morphological and functional data, for example, for transdermal drug diffusion studies. A chemical, structural and temporal characterization of porcine skin in comparison to human skin is not available but will likely improve our understanding of this porcine skin model. Here, we employ Fourier transform infrared (FT-IR) spectroscopic imaging to holistically measure chemical species as well as spatial structure as a function of time to characterize porcine skin as a model for human skin. Porcine skin was found to resemble human skin spectroscopically and differences are elucidated. Cryo-prepared fresh porcine skin samples for spectroscopic imaging were found to be stable over time and small variations are observed. Hence, we extended characterization to the use of this model for dynamic processes. In particular, the capacity and stability of this model in transdermal diffusion is examined. The results indicate that porcine skin is likely to be an attractive tool for studying diffusion dynamics of materials in human skin.

  6. Porcine stress syndrome: an animal model for the neuroleptic malignant syndrome?

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    Keck, P E; Seeler, D C; Pope, H G; McElroy, S L

    1990-07-01

    The porcine stress syndrome is a genetic disorder of swine which, like neuroleptic malignant syndrome, is characterized by hyperthermia, muscle rigidity, and autonomic dysfunction. We investigated the porcine stress syndrome as a possible animal model for neuroleptic malignant syndrome in two ways. First, we administered haloperidol and lithium carbonate, alone and in combination, to susceptible and resistant swine. Second, we attempted to prevent the syndrome by pretreating animals with bromocriptine. Porcine stress syndrome was induced in 2 of 3 susceptible and 1 of 3 resistant swine by combined treatment with lithium and haloperidol, but was not triggered by treatment with lithium or haloperidol alone. Pretreatment with bromocriptine conferred no protection against the syndrome.

  7. Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

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    Christian Fabiansen

    Full Text Available Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12 or a reference diet (AGE-REF, n = 12 for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8. Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5-7 (p ≤ 0.001. There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2-19.7; p = 0.03. However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0-15.9; p < 0.001 in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p < 0.001, whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p < 0.001 and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025.Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

  8. Total laparoscopic gastrocystoplasty: experimental technique in a porcine model

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    Frederico R. Romero

    2007-02-01

    Full Text Available OBJECTIVE: Describe a unique simplified experimental technique for total laparoscopic gastrocystoplasty in a porcine model. MATERIAL AND METHODS: We performed laparoscopic gastrocystoplasty on 10 animals. The gastroepiploic arch was identified and carefully mobilized from its origin at the pylorus to the beginning of the previously demarcated gastric wedge. The gastric segment was resected with sharp dissection. Both gastric suturing and gastrovesical anastomosis were performed with absorbable running sutures. The complete procedure and stages of gastric dissection, gastric closure, and gastrovesical anastomosis were separately timed for each laparoscopic gastrocystoplasty. The end-result of the gastric suturing and the bladder augmentation were evaluated by fluoroscopy or endoscopy. RESULTS: Mean total operative time was 5.2 (range 3.5 - 8 hours: 84.5 (range 62 - 110 minutes for the gastric dissection, 56 (range 28 - 80 minutes for the gastric suturing, and 170.6 (range 70 to 200 minutes for the gastrovesical anastomosis. A cystogram showed a small leakage from the vesical anastomosis in the first two cases. No extravasation from gastric closure was observed in the postoperative gastrogram. CONCLUSIONS: Total laparoscopic gastrocystoplasty is a feasible but complex procedure that currently has limited clinical application. With the increasing use of laparoscopy in reconstructive surgery of the lower urinary tract, gastrocystoplasty may become an attractive option because of its potential advantages over techniques using small and large bowel segments.

  9. Nanomedicine and mammalian sperm: Lessons from the porcine model.

    Science.gov (United States)

    Barkalina, Natalia; Jones, Celine; Coward, Kevin

    2016-01-01

    Biomedical nanotechnology allows us to engineer versatile nanosized platforms that are comparable in size to biological molecules and intracellular organelles. These platforms can be loaded with large amounts of biological cargo, administered systemically and act at a distance, target specific cell populations, undergo intracellular internalization via endogenous uptake mechanisms, and act as contrast agents or release cargo for therapeutic purposes. Over recent years, nanomaterials have been increasingly viewed as favorable candidates for intragamete delivery. Particularly in the case of sperm, nanomaterial-based approaches have been shown to improve the efficacy of existing techniques such as sperm-mediated gene transfer, loading sperm with exogenous proteins, and tagging sperm for subsequent sex- or function-based sorting. In this short review, we provide an outline of the current state of nanotechnology for biomedical applications in reproductive biology and present highlights from a series of our studies evaluating the use of specialized silica nanoparticles in boar sperm as a potential delivery vehicle into mammalian gametes. The encouraging data obtained already from the porcine model in our laboratory have formed the basis for ethical approval of similar experiments in human sperm, thereby bringing us a step closer toward the potential use of this novel technology in the clinical environment.

  10. Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver

    NARCIS (Netherlands)

    di Nicuolo, G.; D'Alessandro, A.; Andria, B.; Scuderi, V.; Scognamiglio, M.; Tammaro, A.; Mancini, A.; Cozzolino, S.; di Florio, E.; Bracco, A.; Calise, F.; Chamuleau, R.A.F.M.

    2010-01-01

    Background: Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive l

  11. Suitability of porcine chondrocyte micromass culture to model osteoarthritis in vitro.

    Science.gov (United States)

    Schlichting, Niels; Dehne, Tilo; Mans, Karsten; Endres, Michaela; Stuhlmüller, Bruno; Sittinger, Michael; Kaps, Christian; Ringe, Jochen

    2014-07-07

    In vitro tissue models are useful tools for the development of novel therapy strategies in cartilage repair and care. The limited availability of human primary tissue and high costs of animal models hamper preclinical tests of innovative substances and techniques. In this study we tested the potential of porcine chondrocyte micromass cultures to mimic human articular cartilage and essential aspects of osteoarthritis (OA) in vitro. Primary chondrocytes were enzymatically isolated from porcine femoral condyles and were maintained in 96-multiwell format to establish micromass cultures in a high-throughput scale. Recombinant porcine tumor necrosis factor alpha (TNF-α) was used to induce OA-like changes documented on histological (Safranin O, collagen type II staining), biochemical (hydroxyproline assay, dimethylmethylene blue method), and gene expression level (Affymetrix porcine microarray, real time PCR) and were compared with published data from human articular cartilage and human micromass cultures. After 14 days in micromass culture, porcine primary chondrocytes produced ECM rich in proteoglycans and collagens. On gene expression level, significant correlations of detected genes with porcine cartilage (r = 0.90), human cartilage (r = 0.71), and human micromass culture (r = 0.75) were observed including 34 cartilage markers such as COL2A1, COMP, and aggrecan. TNF-α stimulation led to significant proteoglycan (-75%) and collagen depletion (-50%). Comparative expression pattern analysis revealed the involvement of catabolic enzymes (MMP1, -2, -13, ADAM10), chemokines (IL8, CCL2, CXCL2, CXCL12, CCXL14), and genes associated with cell death (TNFSF10, PMAIPI, AHR) and skeletal development (GPNMB, FRZB) including transcription factors (WIF1, DLX5, TWIST1) and growth factors (IGFBP1, -3, TGFB1) consistent with published data from human OA cartilage. Expression of genes related to cartilage ECM formation (COL2A1, COL9A1, COMP, aggrecan) as well as hypertrophic bone

  12. Surgical induction of choroidal neovascularization in a porcine model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik;

    2007-01-01

    were compared with the original method. In ten porcine eyes retinal pigment epithelial (RPE) cells were removed using a silicone tipped cannula, in ten porcine eyes Bruch's membrane was perforated once with a retinal perforator without prior RPE removal and in ten eyes RPE removal was followed...... microscopy and by immunohistochemical staining. In addition to these 30 eyes, two eyes underwent surgery with the purpose of subsequent scanning electron microscopic (SEM) examination. RESULTS: In eyes enucleated immediately after surgery neuroretinas overlying the induced lesions were intact without...... apparent atrophy of cells regardless of the surgical technique applied. The process of RPE removal was found to induce breaks in Bruch's membrane and both the size and the number of breaks varied between eyes. CNV membranes were identified in 15 of 15 eyes enucleated after 14 days. CNV membranes induced...

  13. Pathology and biofilm formation in a porcine model of staphylococcal osteomyelitis

    DEFF Research Database (Denmark)

    Johansen, L K; Koch, J; Frees, D;

    2012-01-01

    A porcine model was used to examine the potential of human and porcine Staphylococcus aureus isolates to induce haematogenously spread osteomyelitis. Pigs were inoculated in the right femoral artery with one of the following S. aureus strains: S54F9 (from a porcine lung abscess; n = 3 animals......), NCTC-8325-4 (a laboratory strain of human origin; n = 3 animals) and UAMS-1 (a human osteomyelitis isolate; n = 3 animals). Two pigs were sham inoculated with saline. At 11 or 15 days post infection the animals were scanned by computed tomography before being killed and subjected to necropsy...... examination. Osteomyelitis lesions were present in the right hind limb of all pigs inoculated with strain S54F9 and in one pig inoculated with strain NCTC-8325-4. Microscopically, there was extensive loss of bone tissue with surrounding granulation tissue. Sequestrated bone trabeculae were intermingled...

  14. Ultrasound Evaluation of the Combined Effects of Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model.

    Science.gov (United States)

    Bishop, James H; Fox, James R; Maple, Rhonda; Loretan, Caitlin; Badger, Gary J; Henry, Sharon M; Vizzard, Margaret A; Langevin, Helene M

    2016-01-01

    The persistence of back pain following acute back "sprains" is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a "hobble" device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted.

  15. Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Damir Hamamdzic

    2013-01-01

    Full Text Available Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9 gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

  16. Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes

    NARCIS (Netherlands)

    Heuvel, van den M.; Sorop, O.; Koopmans, S.J.; Dekker, R.A.; Vries, de R.; Beusekom, H.M.M.; Eringa, E.C.; Duncker, D.J.; Danser, A.H.J.; Giessen, W.J.

    2012-01-01

    Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptoz

  17. Brief report: biomarkers of aortic vascular prosthetic graft infection in a porcine model with Staphylococcus aureus

    DEFF Research Database (Denmark)

    Langerhuus, S. N.; Tønnesen, E. K.; Jensen, K. H.;

    2010-01-01

    Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP...

  18. Laser-driven short-duration heating angioplasty: chronic artery lumen patency and histology in porcine iliac artery

    Science.gov (United States)

    Shimazaki, Natsumi; Kunio, Mie; Naruse, Sho; Arai, Tsunenori; Sakurada, Masami

    2012-02-01

    We proposed a short-duration heating balloon angioplasty. We designed a prototype short-duration heating balloon catheter that can heat artery media to 60-70°C within 15-25 s with a combination of laser-driven heat generation and continuous fluid irrigation in the balloon. The purpose of this study was to investigate chronic artery lumen patency as well as histological alteration of artery wall after the short-duration heating balloon dilatation with porcine healthy iliac artery. The short-term heating balloon dilated sites were angiographically patent in acute (1 hour) and in chronic phases (1 and 4 weeks). One week after the dilatation, smooth muscle cells (SMCs) density in the artery media measured from H&E-stained specimens was approx. 20% lower than that in the reference artery. One and four weeks after the dilatations, normal structure of artery adventitia was maintained without any incidence of thermal injury. Normal lamellar structure of the artery media was also maintained. We found that the localized heating restricted to artery media by the short-duration heating could maintain adventitial function and artery normal structure in chronic phase.

  19. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.

    Science.gov (United States)

    Lucke, Silke; Hoene, Andreas; Walschus, Uwe; Kob, Anette; Pissarek, Jens-Wolfgang; Schlosser, Michael

    2015-01-01

    Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX) were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells) were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like) macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like) macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.

  20. Acute and Chronic Local Inflammatory Reaction after Implantation of Different Extracellular Porcine Dermis Collagen Matrices in Rats

    Directory of Open Access Journals (Sweden)

    Silke Lucke

    2015-01-01

    Full Text Available Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.

  1. Porcine models of digestive disease: the future of large animal translational research

    OpenAIRE

    Gonzalez, Liara M.; Moeser, Adam J; Blikslager, Anthony T.

    2015-01-01

    There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such ...

  2. The Effectiveness of Porcine Dermal Collagen (Permacol(®)) on Wound Healing in the Rat Model.

    Science.gov (United States)

    Kalin, Murat; Kuru, Serdar; Kismet, Kemal; Barlas, Aziz Mutlu; Akgun, Yusuf Akif; Astarci, Hesna Muzeyyen; Ustun, Huseyin; Ertas, Ertugrul

    2015-12-01

    Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now. The aim of this study is to investigate the effectiveness of PDC on wound healing as a dermal substitute in the rat model. Twenty Wistar albino rats were divided into two groups. Standard full-thickness skin defects were created on the back of the rats. In the control group (Group 1), the dressings moisturized with saline were changed daily. In the study group (Group 2), porcine dermal collagen was implanted onto each wound and fixed with 4-0 polypropylene sutures. Contraction percentages of wound areas were calculated on the third, seventh, tenth, and fourteenth days by using the planimetric program. On fourteenth day, the wound areas were excised for histopathological examination, inflammatory scoring, and evaluation of collagen deposition. The study group was superior to the control group in terms of inflammatory scoring, type I/type III collagen ratio, and wound contraction rates. Porcine dermal collagen may be used effectively and safely on full-thickness wounds as a current dermal substitute.

  3. Pharmacological Attenuation of Myocardial Reperfusion Injury in a Closed-Chest Porcine Model

    DEFF Research Database (Denmark)

    Ekeløf, Sarah; Rosenberg, Jacob; Jensen, Jan Skov;

    2014-01-01

    Myocardial ischemia-reperfusion injury is a clinical challenge in interventional cardiology, and at the moment, no pharmacological agent is universally accepted in the prevention. In order to prevent inappropriate clinical trials, a potential pharmacological agent should be proved reproducibly...... effective in clinically relevant experimental studies before initiation of human studies. The closed-chest porcine model is a promising experimental model of ischemia-reperfusion injury. The purpose of this systematic review was to describe the pharmacological treatments evaluated in the closed...

  4. Chronic high glucose inhibits albumin reabsorption by lysosomal alkalinization in cultured porcine proximal tubular epithelial cells (LLC-PK1).

    Science.gov (United States)

    Ishibashi, Fukashi

    2006-06-01

    Lysosomal acidification is a key step of albumin reabsorption in proximal tubular epithelial cells (PTECs). This study was performed to examine the influence of chronic high glucose on lysosomal acidification in cultured PTECs. Porcine PTECs (LLC-PK(1) cells) were cultured in 16.7 mM (300 mg/dl) glucose (HG) alone or with 0.5 mM phlorizin for 24 weeks and subsequently for 12 weeks in 5.5 mM (100 mg/dl) glucose (NG). Chronic HG inhibited the fluorescein isothiocyanate (FITC)-albumin (A) uptake progressively, while phlorizin reversed the inhibition. NG for 12 weeks after HG normalized the uptake. The time-dependent uptake of FITC-A was inhibited by HG and bafilomycin A(1) (BafA(1)) after 15 min and by 4,4'-diisothiocyanato-2,2'-disulfonic acid (DIDS) and N-ethyl-N-isopropyl-amiloride (EIPA) after 3 min. Cellular ATP was depleted by HG and restored by NG. Lysosomal pH, assessed by an acidotropic fluorescent probe, was alkalinized (pH 4.5-7.8) with 5.5-27.8 mM glucose and normalized by subsequent NG. BafA(1) alkalinized lysosomes, and the concentration required to 50% change for the pH and 50% inhibition of FITC-A uptake was similar. EIPA inhibited FITC-A uptake, but did not influence lysosomal pH. DIDS inhibited FITC-A uptake, and unexpectedly lowered lysosomal pH. Real time PCR showed that HG reduced the mRNA level for vacuolar H(+)-ATPase, but did not alter those of chloride channel-5 and Na(+)-H(+)-exchanger-3. In conclusion, the chronic HG inhibits albumin reabsorption by lysosomal alkalinization in PTECs, probably due to ATP depletion and down-regulation of vacuolar H(+)-ATPase.

  5. 慢性发绀型肺血减少先天性心脏病幼猪模型的建立与病理学观察%Development and pathological observation on a chronic cyanotic porcine model with decreased pulmonary blood flow

    Institute of Scientific and Technical Information of China (English)

    王栋; 刘迎龙; 吕小东; 朱耀斌; 凌锋; 刘爱军; 李刚; 续玉林

    2011-01-01

    .09) mmHg ( 1 mmHg =0.133 kpa) to ( 19.67 ± 4.76) mmHg after 4 weeks ( P = 0.011) . The arterial oxygen saturation ( SaO2) . arterial oxygen tension ( PaO2 ) , arterial carhon dioxide tension ( PaCO2 ) , hemoglobin concentration ( Hb) and hematocrit value ( Hct) were 82.35%, 68.73 mmHg , 51.83 mmHg, 13.82 g/dl and 42.67% in cyanotic model group versus 96.43% , 194.08 mmHg, 36.9 mmHg, 10.98 g/dl and 31.17% in control group, respectively ( all P <0.05) . There were significant pathologic differences of lung and heart tissue between the two groups. Conclusion : A chronic porcine model of cyanotic congenital heart disease with decreased pulmonary blood flow was successfully established by right-to-left shunting with a PA-to-LA synthetic graft with PA banding. Application of this experimental design may enhance our understanding and possibly influence the treatment of patients having congenital cyanotic heart disease with decreased pulmonary blood flow.

  6. Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Rehling, Michael;

    2005-01-01

    by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion). RESULTS: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically...... of reperfusion in our porcine model....

  7. Establishment and characterization of a differentiated epithelial cell culture model derived from the porcine cervix uteri

    Directory of Open Access Journals (Sweden)

    Miessen Katrin

    2012-03-01

    Full Text Available Abstract Background Cervical uterine epithelial cells maintain a physiological and pathogen-free milieu in the female mammalian reproductive tract and are involved in sperm-epithelium interaction. Easily accessible, differentiated model systems of the cervical epithelium are not yet available to elucidate the underlying molecular mechanisms within these highly specialized cells. Therefore, the aim of the study was to establish a cell culture of the porcine cervical epithelium representing in vivo-like properties of the tissue. Results We tested different isolation methods and culture conditions and validated purity of the cultured cells by immunohistochemistry against keratins. We could reproducibly culture pure epithelial cells from cervical tissue explants. Based on a morphology score and the WST-1 Proliferation Assay, we optimized the growth medium composition. Primary porcine cervical cells performed best in conditioned Ham's F-12, containing 10% FCS, EGF and insulin. After cultivation in an air-liquid interface for three weeks, the cells showed a discontinuously multilayered phenotype. Finally, differentiation was validated via immunohistochemistry against beta catenin. Mucopolysaccharide production could be shown via alcian blue staining. Conclusions We provide the first suitable protocol to establish a differentiated porcine epithelial model of the cervix uteri, based on easily accessible cells using slaughterhouse material.

  8. Identification of QTL for dorso-caudal chronic pleuritis in 12 crossbred porcine families

    DEFF Research Database (Denmark)

    Gregersen, V R; Sørensen, K K; Christensen, O F

    2010-01-01

    Pleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker-assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait...

  9. Proteomic changes of the porcine small intestine in response to chronic heat stress.

    Science.gov (United States)

    Cui, Yanjun; Gu, Xianhong

    2015-12-01

    Acute heat stress (HS) negatively affects intestinal integrity and barrier function. In contrast, chronic mild HS poses a distinct challenge to animals. Therefore, this study integrates biochemical, histological and proteomic approaches to investigate the effects of chronic HS on the intestine in finishing pigs. Castrated male crossbreeds (79.00 ± 1.50 kg BW) were subjected to either thermal neutral (TN, 21 °C; 55% ± 5% humidity; n=8) or HS conditions (30 °C; 55% ± 5% humidity; n=8) for 3 weeks. The pigs were sacrificed after 3 weeks of high environmental exposure and the plasma hormones, the intestinal morphology, integrity, and protein profiles of the jejunum mucosa were determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS damaged intestinal morphology, increased plasma d-lactate concentrations and decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis of the jejunum mucosa was conducted by 2D gel electrophoresis and mass spectrometry. Fifty-three intestinal proteins were found to be differentially abundant, 18 of which were related to cell structure and motility, and their changes in abundance could comprise intestinal integrity and function. The down-regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron transport chain (ETC), and oxidative phosphorylation suggested that chronic HS impaired energy metabolism and thus induced oxidative stress. Moreover, the changes of ten proteins in abundance related to stress response and defense indicated pigs mediated long-term heat exposure and counteracted its negative effects of heat exposure. These findings have important implications for understanding the effect of chronic HS on intestines.

  10. Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

    Directory of Open Access Journals (Sweden)

    Cai-Jun Wu

    2015-01-01

    Full Text Available Background: Animal models of asphyxiation cardiac arrest (ACA are frequently used in basic research to mirror the clinical course of cardiac arrest (CA. The rates of the return of spontaneous circulation (ROSC in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic (ROC curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983, and the optimum cut-off value was 15.62 (specificity 95.7% and sensitivity 80.0%. Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

  11. A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.

    Science.gov (United States)

    Beraldi, Rosanna; Chan, Chun-Hung; Rogers, Christopher S; Kovács, Attila D; Meyerholz, David K; Trantzas, Constantin; Lambertz, Allyn M; Darbro, Benjamin W; Weber, Krystal L; White, Katherine A M; Rheeden, Richard V; Kruer, Michael C; Dacken, Brian A; Wang, Xiao-Jun; Davis, Bryan T; Rohret, Judy A; Struzynski, Jason T; Rohret, Frank A; Weimer, Jill M; Pearce, David A

    2015-11-15

    Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions.

  12. Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro

    DEFF Research Database (Denmark)

    Nielsen, Hanne Mørck; Rassing, Margrethe Rømer

    2002-01-01

    The present study was conducted to investigate and compare the effect of pH and drug concentration on nicotine permeability across the TR146 cell culture model and porcine buccal mucosa in vitro. As a further characterization of the TR146 cell culture model, it was explored whether the results were...... comparable for bi-directional and uni-directional transport in the presence of a transmembrane pH gradient. Nicotine concentrations between 10(-5) and 10(-2) M were applied to the apical side of the TR146 cell culture model or the mucosal side of porcine buccal mucosa. Buffers with pH values of 5.5, 7...... concentrations of nicotine, the P(app) values decreased, which can partly be explained by an effect on the paracellular pathway. Similar results were also obtained when using the models for bi-directional as well as for uni-directional studies. The TR146 cell culture model may be used as model for buccal...

  13. Evaluation of a Model-Based Hemodynamic Monitoring Method in a Porcine Study of Septic Shock

    Directory of Open Access Journals (Sweden)

    James A. Revie

    2013-01-01

    Full Text Available Introduction. The accuracy and clinical applicability of an improved model-based system for tracking hemodynamic changes is assessed in an animal study on septic shock. Methods. This study used cardiovascular measurements recorded during a porcine trial studying the efficacy of large-pore hemofiltration for treating septic shock. Four Pietrain pigs were instrumented and induced with septic shock. A subset of the measured data, representing clinically available measurements, was used to identify subject-specific cardiovascular models. These models were then validated against the remaining measurements. Results. The system accurately matched independent measures of left and right ventricle end diastolic volumes and maximum left and right ventricular pressures to percentage errors less than 20% (except for the 95th percentile error in maximum right ventricular pressure and all R2>0.76. An average decrease of 42% in systemic resistance, a main cardiovascular consequence of septic shock, was observed 120 minutes after the infusion of the endotoxin, consistent with experimentally measured trends. Moreover, modelled temporal trends in right ventricular end systolic elastance and afterload tracked changes in corresponding experimentally derived metrics. Conclusions. These results demonstrate that this model-based method can monitor disease-dependent changes in preload, afterload, and contractility in porcine study of septic shock.

  14. A porcine model of acute, haematogenous, localized osteomyelitis due to Staphylococcus aureus

    DEFF Research Database (Denmark)

    Johansen, Louise Kruse; Frees, Dorte; Aalbæk, Bent;

    2011-01-01

    A porcine model of acute, haematogenous, localized osteomyelitis was established. Serial dilutions of Staphylococcus aureus [5–50–500–5000–50 000 CFU/kg body weight (BW) suspended in saline or saline alone] were inoculated into the right brachial artery of pigs (BW 15 kg) separated into six groups...... of two animals. During the infection, blood was collected for cultivation, and after the animals were killed from day 5 to 15, they were necropsied and tissues were sampled for histopathology. Animals receiving =500 CFU/kg BW were free of lesions. Pigs inoculated with 5000 and 50 000 CFU/kg BW only...

  15. Identification of QTL for dorso-caudal chronic pleuritis in 12 crossbred porcine families.

    Science.gov (United States)

    Gregersen, V R; Sørensen, K K; Christensen, O F; Busch, M E; Vingborg, R K K; Velander, I H; Lund, M S; Bendixen, C

    2010-10-01

    Pleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker-assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait loci (QTL) or markers associated with the prevalence of CP should be identified. In this study, 7470 pigs from crosses between 12 Danish Duroc boars and 604 sows (Danish Landrace × Danish Large White) were evaluated for CP located on the dorso-caudal part of the lungs. Quantitative trait loci were identified within boar families using both a Binomial logistic regression method and a chi-square test of association. Significant QTL for CP were detected on Sus scrofa chromosomes (SSC) 2, 8, 12, 13, 14 and 18 using both methods. One QTL on SSC 8 was also detected across families. For the QTL identified within families, the odds-ratio of having CP was approximately twice as high for the unfavourable allele compared to the favourable one. These QTL and closely linked markers show promise for the development of gene-specific markers associated with a reduced incidence of CP located on the dorso-caudal part of the lungs.

  16. Using an automated emboli detection device in a porcine cardiopulmonary bypass (CPB) model: feasibility and considerations.

    Science.gov (United States)

    Schnürer, Christian; Gyoeri, Georg; Hager, Martina; Jeller, Anton; Moser, Patrizia L; Velik-Salchner, Corinna; Laufer, Guenther; Lorenz, Ingo H; Kolbitsch, Christian

    2007-12-01

    The significant risk of cerebral embolism during cardiopulmonary bypass (CPB) makes monitoring of embolic events advisable already when developing new operation and coagulation management strategies for example in CPB animal models. The present study therefore evaluated in a porcine CPB model the feasibility of bilateral epicarotid Doppler signal recording and the quality of manual or automatic emboli detection. A total of 42 recordings (e.g. right carotid artery (n = 20), left carotid artery (n = 22)) were evaluated. The frequency of emboli counts was comparable for both carotid arteries. Automatic emboli detection, however, found significantly more embolic events per pig than did post-hoc manual off-line analysis of the recordings (172 +/- 217 vs. 13 +/-10). None of the brains, however, showed any emboli or infarction area either in cross-examination or in histological evaluation. In conclusion, the present study showed the feasibility of using an epicarotid Doppler device for bilateral emboli detection in a porcine CPB model. Automatic on-line emboli detection, however, reported more embolic events than did post hoc, off-line manual analysis. Possible reasons for this discrepancy are discussed.

  17. Prophylactic Fasciotomy in a Porcine Model of Extremity Trauma

    Science.gov (United States)

    2014-07-16

    study used female Yorkshire swine of weights ranging from 70e90 kg (Sus scrofa ; Midwest Research Swine, Gibbon, MN). On arrival, swine were housed for...model (Sus scrofa ) of extremity ischemia/ j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 3 ( 2 0 1 5 ) 4 4 9e4 5 7456 reperfusion and

  18. Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis

    Science.gov (United States)

    Fleury, Agnès; Trejo, Armando; Cisneros, Humberto; García-Navarrete, Roberto; Villalobos, Nelly; Hernández, Marisela; Villeda Hernández, Juana; Hernández, Beatriz; Rosas, Gabriela; Bobes, Raul J.; S. de Aluja, Aline; Sciutto, Edda; Fragoso, Gladis

    2015-01-01

    Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 oncospheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments. PMID:26252878

  19. Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis.

    Directory of Open Access Journals (Sweden)

    Agnès Fleury

    Full Text Available Human neurocysticercosis (NC is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000 were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres to 5.4% (500 oncospheres. Most parasites were caseous or calcified (38/63, 60.3% and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments.

  20. Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis.

    Science.gov (United States)

    Fleury, Agnès; Trejo, Armando; Cisneros, Humberto; García-Navarrete, Roberto; Villalobos, Nelly; Hernández, Marisela; Villeda Hernández, Juana; Hernández, Beatriz; Rosas, Gabriela; Bobes, Raul J; de Aluja, Aline S; Sciutto, Edda; Fragoso, Gladis

    2015-01-01

    Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 oncospheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments.

  1. Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model

    Institute of Scientific and Technical Information of China (English)

    Mitsugi Shimoda; Yoshimi Iwasaki; Toshie Okada; Keiichi Kubota

    2012-01-01

    AIM:To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.METHODS:One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes.A 40% left hepatectomy was performed after reperfusion.Six animals received Edr (3 mg/kg per hour)intravenously and six control animals received saline just before reperfusion.Remnant liver volume,hemodynamics,aspartate aminotransferase (AST),alanine aminotransferase,lactate dehydrogenase and lactic acid,were compared between the groups.The expression of transforming growth factor-β (TGF-β1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction.Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining,respectively.RESULTS:Serum AST (P =0.029),and toll like receptor 4 level (P =0.043) were significantly lower after 3 hin animals receiving Edr.In addition,TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs.After mo,all factors were non-significantly different between the two groups.CONCLUSION:Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

  2. Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

    Science.gov (United States)

    Schnürer, C; Hager, M; Györi, G; Velik-Salchner, C; Moser, P L; Laufer, G; Lorenz, I H; Kolbitsch, C

    2011-02-01

    In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model.

  3. An ex vivo porcine nasal mucosa explants model to study MRSA colonization.

    Directory of Open Access Journals (Sweden)

    Pawel Tulinski

    Full Text Available Staphylococcus aureus is an opportunistic pathogen able to colonize the upper respiratory tract and skin surfaces in mammals. Methicillin-resistant S. aureus ST398 is prevalent in pigs in Europe and North America. However, the mechanism of successful pig colonization by MRSA ST398 is poorly understood. To study MRSA colonization in pigs, an ex vivo model consisting of porcine nasal mucosa explants cultured at an air-liquid interface was evaluated. In cultured mucosa explants from the surfaces of the ventral turbinates and septum of the pig nose no changes in cell morphology and viability were observed up to 72 h. MRSA colonization on the explants was evaluated followed for three MRSA ST398 isolates for 180 minutes. The explants were incubated with 3×10(8 CFU/ml in PBS for 2 h to allow bacteria to adhere to the explants surface. Next the explants were washed and in the first 30 minutes post adhering time, a decline in the number of CFU was observed for all MRSA. Subsequently, the isolates showed either: bacterial growth, no growth, or a further reduction in bacterial numbers. The MRSA were either localized as clusters between the cilia or as single bacteria on the cilia surface. No morphological changes in the epithelium layer were observed during the incubation with MRSA. We conclude that porcine nasal mucosa explants are a valuable ex vivo model to unravel the interaction of MRSA with nasal tissue.

  4. Porcine retinal cell line VIDO R1 and Chlamydia suis to modelize ocular chlamydiosis.

    Science.gov (United States)

    Käser, Tobias; Cnudde, Thomas; Hamonic, Glenn; Rieder, Meghanne; Pasternak, J Alex; Lai, Ken; Tikoo, Suresh K; Wilson, Heather L; Meurens, François

    2015-08-15

    Human ocular Chlamydia trachomatis infections can lead to trachoma, the major cause of infectious blindness worldwide. Trachoma control strategies are very helpful but logistically challenging, and a trachoma vaccine is needed but not available. Pigs are a valuable large animal model for various immunological questions and could facilitate the study of human ocular chlamydial infections. In addition, a recent study identified the zoonotic potential of Chlamydia suis, the natural pathogen of pigs. In terms of the One Health Initiative, understanding the host-pathogen-interactions and finding a vaccine for porcine chlamydia infections would also benefit human health. Thus, we infected the porcine retinal cell line VIDO R1 with C. suis and analyzed the chlamydial life cycle and the innate immune response of the infected cells. Our results indicate that C. suis completes its life cycle in VIDO R1 cells within 48 h, comparable to C. trachomatis in humans. C. suis infection of VIDO R1 cells led to increased levels of various innate immune mediators like pathogen recognition receptors, cytokines and chemokines including IL6, TNFα, and MMP9, also most relevant in human C. trachomatis infections. These results illustrate the first steps in the host-pathogen-interactions of ocular C. suis infections in pigs and show their similarity to C. trachomatis infections in humans, justifying further testing of pigs as an animal model for human trachoma.

  5. Percentile growth charts for biomedical studies using a porcine model.

    Science.gov (United States)

    Corson, A M; Laws, J; Laws, A; Litten, J C; Lean, I J; Clarke, L

    2008-12-01

    Increasing rates of obesity and heart disease are compromising quality of life for a growing number of people. There is much research linking adult disease with the growth and development both in utero and during the first year of life. The pig is an ideal model for studying the origins of developmental programming. The objective of this paper was to construct percentile growth curves for the pig for use in biomedical studies. The body weight (BW) of pigs was recorded from birth to 150 days of age and their crown-to-rump length was measured over the neonatal period to enable the ponderal index (PI; kg/m3) to be calculated. Data were normalised and percentile curves were constructed using Cole's lambda-mu-sigma (LMS) method for BW and PI. The construction of these percentile charts for use in biomedical research will allow a more detailed and precise tracking of growth and development of individual pigs under experimental conditions.

  6. Percutaneous transgastric endoscopic tube ileostomy in a porcine survival model

    Science.gov (United States)

    Shi, Hong; Chen, Su-Yu; Wang, Yong-Guang; Jiang, Sheng-Jun; Cai, He-Li; Lin, Kai; Xie, Zhao-Fei; Dong, Fen-Fang

    2016-01-01

    AIM To introduce natural orifice transgastric endoscopic surgery (NOTES) tube ileostomy using pelvis-directed submucosal tunneling endoscopic gastrostomy and endoscopic tube ileostomy. METHODS Six live pigs (three each in the non-survival and survival groups) were used. A double-channeled therapeutic endoscope was introduced perorally into the stomach. A gastrostomy was made using a 2-cm transversal mucosal incision following the creation of a 5-cm longitudinal pelvis-directed submucosal tunnel. The pneumoperitoneum was established via the endoscope. In the initial three operations of the series, a laparoscope was transumbilically inserted for guiding the tunnel direction, intraperitoneal spatial orientation and distal ileum identification. Endoscopic tube ileostomy was conducted by adopting an introducer method and using a Percutaneous Endoscopic Gastrostomy Catheter Kit equipped with the Loop Fixture. The distal tip of the 15 Fr catheter was placed toward the proximal limb of the ileum to optimize intestinal content drainage. Finally, the tunnel entrance of the gastrostomy was closed using nylon endoloops with the aid of a twin grasper. The gross and histopathological integrity of gastrostomy closure and the abdominal wall-ileum stoma tract formation were assessed 1 wk after the operation. RESULTS Transgastric endoscopic tube ileostomy was successful in all six pigs, without major bleeding. The mean operating time was 71 min (range: 60-110 min). There were no intraoperative complications or hemodynamic instability. The post-mortem, which was conducted 1-wk postoperatively, showed complete healing of the gastrostomy and adequate stoma tract formation of ileostomy. CONCLUSION Transgastric endoscopic tube ileostomy is technically feasible and reproducible in an animal model, and this technique is worthy of further improvement. PMID:27729743

  7. Snatch-farrowed, porcine-colostrum-deprived (SF-pCD) pigs as a model for swine infectious disease research.

    Science.gov (United States)

    Huang, Yanyun; Haines, Deborah M; Harding, John C S

    2013-04-01

    The current study tested the benefit of commercially available spray-dried bovine colostrum (The Saskatoon Colostrum Company, Saskatoon, Saskatchewan) in raising snatch-farrowed, porcine-colostrum-deprived (SF-pCD) pigs. In experiment 1, 12 SF-pCD pigs received a liquid diet composed mainly of bovine colostrum from birth to day 10; 6 remained on the same liquid diet (COL), and the other 6 were fed a diet composed mainly of milk replacer (RPL) until weaning. In experiment 2, 12 SF-pCD pigs were fed mainly bovine colostrum before weaning; after weaning, 6 were fed a starter diet containing 20% (w/w) bovine colostrum powder (STARTER-COL), and the other 6 were fed a starter diet without any bovine colostrum (STARTER-CTRL) until termination (day 42 or day 49). In experiment 1 the COL pigs had significantly fewer fever-days than did the RPL pigs. In experiment 2 diarrhea, typhlocolitis, and pancreatic degeneration developed in 4 of the STARTER-COL pigs after weaning. In both experiments all the pigs fed mainly bovine colostrum before weaning survived until termination. All pigs tested free of swine influenza virus H1N1 and H3N2, Porcine reproductive and respiratory syndrome virus, and Porcine parvovirus. In experiment 2 all the pigs tested free of Porcine circovirus type 2 (PCV2), but some in both groups tested positive for Torque teno virus genogroups 1 and 2. In conclusion, with the use of snatch-farrowing and bovine colostrum, pigs can be raised in the absence of porcine maternal antibodies with 100% survival and freedom from most porcine pathogens of biologic relevance. This model is potentially suitable for animal disease research.

  8. Rosiglitazone dampens pulmonary inflammation in a porcine model of acute lung injury.

    Science.gov (United States)

    Mirakaj, Valbona; Mutz, Christian; Vagts, Dierk; Henes, Janek; Haeberle, Helene A; Husung, Susanne; König, Tony; Nöldge-Schomburg, Gabriele; Rosenberger, Peter

    2014-08-01

    The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.

  9. Models of acute and chronic pancreatitis.

    Science.gov (United States)

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  10. Cavitation-enhanced delivery of insulin in agar and porcine models of human skin.

    Science.gov (United States)

    Feiszthuber, Helga; Bhatnagar, Sunali; Gyöngy, Miklós; Coussios, Constantin-C

    2015-03-21

    Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery. Fluorescently stained, soluble Actrapid insulin was placed on the surface of human skin-mimicking materials subjected to 265 kHz, 10% duty cycle focused ultrasound. A confocally and coaxially aligned 5 MHz broadband ultrasound transducer was used to detect cavitation. Two different skin models were used. The first model, 3% agar hydrogel, was insonated with a range of pressures (0.25-1.40 MPa peak rarefactional focal pressure-PRFP), with and without cavitation nuclei embedded within the agar at a concentration of 0.05% w/v. The second, porcine skin was insonated at 1.00 and 1.40 MPa PRFP. In both models, fluorescence measurements were used to determine penetration depth and concentration of delivered insulin. Results show that in agar gel, both insulin penetration depth and concentration only increased significantly in the presence of inertial cavitation, with up to a 40% enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ultrasound compared to the control samples, but there was no significant increase in penetration distance. The results underline the importance of instigating and monitoring inertial cavitation during transdermal insulin delivery.

  11. Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest

    Directory of Open Access Journals (Sweden)

    Anton Amann

    2001-01-01

    Full Text Available In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-γ induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC and radioimmunoassay (RIA (BRAHMS Diagnostica, Berlin, Germany. Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false positive results. The mean serum tryptophan concentration was 39.0 Ī 6.2 μmol/l, and the mean kynurenine concentration was 0.85 Ī 0.33 μmol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7Ī 8.4 nmol/μmol, and that in plasma was 20.7Ī 9.5 nmol/μmol (n = 7, which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation.

  12. Lack of cardioprotection from metabolic support with glutamine or glutamate in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Mortensen, Ulrik;

    2005-01-01

    OBJECTIVE: Previous experimental studies indicate that glutamine or glutamate may provide cardioprotection by improving the oxidative metabolism in myocardial ischemia. We investigated the effect of glutamine or glutamate, given during reperfusion, on resulting infarct size and hemodynamic recovery...... vascular resistance, while glutamate preserved cardiac output during infusion. CONCLUSION: Substrate supplementation with the anaplerotic precursors glutamine and glutamate is ineffective as adjunctive therapy for severe myocardial ischemia. Beneficial effects documented in less complex experimental....... DESIGN: A porcine coronary occlusion model was applied. Infusions were initiated 15 min before reperfusion and supplemented with intracoronary bolus doses at reperfusion. The primary outcome measure was infarct size in relation to area at risk determined by a standard tissue staining procedure. Secondary...

  13. Analysis of regional compliance in a porcine model of acute lung injury.

    Science.gov (United States)

    Czaplik, Michael; Biener, Ingeborg; Dembinski, Rolf; Pelosi, Paolo; Soodt, Thomas; Schroeder, Wolfgang; Leonhardt, Steffen; Marx, Gernot; Rossaint, Rolf; Bickenbach, Johannes

    2012-10-15

    Lung protective ventilation in acute lung injury (ALI) focuses on using low tidal volumes and adequate levels of positive end-expiratory pressure (PEEP). Identifying optimal pressure is difficult because pressure-volume (PV) relations differ regionally. Precise analysis demands local measurements of pressures and related alveolar morphologies. In a porcine model of surfactant depletion (n=24), we combined measuring static pressures with endoscopic microscopy and electrical impedance tomography (EIT) to examine regional PV loops and morphologic heterogeneities between healthy (control group; CON) and ALI lungs ventilated with low (LVT) or high tidal volumes (HVT). Quantification included indices for microscopy (Volume Air Index (VAI), Heterogeneity and Circularity Index), EIT analysis and calculation of regional compliances due to generated PV loops. We found that: (1) VAI decreased in lower lobe after ALI, (2) electrical impedance decreased in dorsal regions and (3) PV loops differed regionally. Further studies should prove the potentials of these techniques on individual respiratory settings and clinical outcome.

  14. A Porcine Liver Model for Validation of Registration Accuracy in Image-Guided Surgery

    Science.gov (United States)

    Peterhans, Matthias; Dagon, Benoît; Berg, Anne Vom; Inderbitzin, Daniel; Baur, Charles; Weber, Stefan

    Correct registration between pre-operative high-resolution images and intra-operative data of lower detail is a fundamental requirement in image-guided liver surgery. We propose a multi modality liver model for measuring the accuracy of such registration methods. A freshly explanted porcine liver is artificially perfused by a peristaltic pump and liver motion is simulated by means of inflatable objects positioned around the liver. Co-registered ultrasound and CT data sets are acquired in different deformation scenarios and allow compar-ing registration outcomes with a CT data set serving as ground truth. The pre-sent work describes the experimental setup and summarizes the results from ultrasound and CT imaging.

  15. Failure of intravenous metoprolol to limit acute myocardial infarct size in a nonreperfused porcine model.

    Science.gov (United States)

    Kern, K B; Hilwig, R W; Warner, A; Basnight, M; Ewy, G A

    1995-04-01

    The usefulness of intravenous beta-adrenergic receptor blockade in limiting infarct size when neither reperfusion nor collateral flow occurs is unknown. The effect of intravenous metoprolol on limiting myocardial infarct size was therefore examined in a nonreperfused porcine model. Closed-chest techniques were used to occlude the left anterior descending coronary artery, after which animals were randomized at 20 minutes to receive intravenous metoprolol, 0.75 mg/kg, or placebo. Infarct size examined at 5 hours with Evans blue and triphenyltetrazolium staining techniques was expressed as a percentage of total ventricular myocardium at ischemic risk. This percentage was not significantly different between the groups (84% +/- 5% with metoprolol vs 90% +/- 4% with placebo; p = 0.4). Myocardial infarct size was not significantly decreased at 5 hours by early administration of intravenous metoprolol when the infarct artery remained occluded and collateral flow was minimal.

  16. Effects of chest compressions on cardiorespiratory function in a non-arrested porcine model

    Institute of Scientific and Technical Information of China (English)

    CONG Lu-hong; LI Chun-sheng; GUO Zhi-jun; WANG Shuo; WU Jun-yuan; YUAN Wei

    2013-01-01

    Background The effects of chest compressions to hemodynamic and respiratory parameters during hands-only cardiopulmonary resuscitation (CPR) in a non-arrested patient who suddenly collapses are confusing.In this research,we investigated the effects of chest compressions in a non-arrested porcine model.Methods Fourteen male domestic pigs were randomized into sham control group (SHAM group,only anesthetized and instrumented without chest compression,n=6) or chest compression group (CC group,2 minutes of chest compressions,n=8).Continuous hemodynamic parameters,dynamic lung compliance (Cdyn),and blood gas analysis outcomes were recorded.Serum levels of catecholamine were measured at baseline and 2 minutes,30 minutes,4 hours,and 24 hours after chest compressions.Chest computed tomography (CT) was performed at 30 minutes and 24 hours.Conventional histopathology evaluation was performed.Results After two minutes of chest compressions in the CC group,heart rate and extravascular lung water increased significantly; mean arterial pressure,stroke volume,and global ejection fraction significantly decreased.Cdyn significantly decreased to valley levels at 30 minutes and slowly recovered.Compared with the baseline,serum levels of catecholamine significantly increased at 2 minutes and rapidly decreased 24 hours later.At 30 minutes after chest compressions,chest CT showed local exudation,which was absorbed 24 hours later.Conclusions This research showed that 2 minutes of chest compressions causes various heart and lung tissue damage in the normal a normal porcine model.It also impacts the hemodynamic and Cdyn.

  17. Comparison between cryopreserved and glycerol-preserved allografts in a partial-thickness porcine wound model.

    Science.gov (United States)

    Yoon, Cheonjae; Lim, Kihwan; Lee, Sungjun; Choi, Yanghwan; Choi, Youngwhan; Lee, Jungsuk

    2016-03-01

    Human skin allografts are one of the best temporary biological coverings for severely burned patients. Cryopreserved (CPA) and glycerol-preserved (GPA) allografts are the most widely used types. This study compared the allograft efficiency of both preservation methods under the same conditions. To simulate actual clinical conditions, we used a porcine wound model. In addition, we evaluated the macroscopic and microscopic scoring of graft performance for each method. Porcine cadaver skin 1 mm thick was obtained from one pig. Cryopreserved skin cell viability was 20.8 %, glycerol-preserved skin was 9.08 %, and fresh skin was 58.6 %. We made ten partial-thickness wounds each in two pigs. The take rates on day 2 were 96.23 and 82.65 % in the GPA and CPA group (both n = 9), respectively. After 1 week, the take rates of both groups were nearly equal. The removal rate at week 5 was 98.87 and 94.41 % in the GPA and CPA group, respectively. On microscopic findings at week 2, inflammation was greater in the CPA group. Other findings such as fibroblast hyperplasia and neovascularization were not significantly different between both groups. At week 5, the score of collagen fiber synthesis was 2.67 ± 0.47 and 2.33 ± 0.47 in the GPA and CPA group, respectively. The epidermal-dermal junction was 2.22 ± 0.79 and 2.00 ± 0.47 in the GPA and CPA group, respectively. These findings suggest that wound healing takes longer in the CPA group. The preservation method of allografts is not a absolute factor in the wound healing process in this wound model.

  18. Novel A20-gene-eluting stent inhibits carotid artery restenosis in a porcine model

    Directory of Open Access Journals (Sweden)

    Zhou ZH

    2016-08-01

    Full Text Available Zhen-hua Zhou,1 Jing Peng,1 Zhao-you Meng,1 Lin Chen,1 Jia-Lu Huang,1 He-qing Huang,1 Li Li,2 Wen Zeng,2 Yong Wei,2 Chu-Hong Zhu,2 Kang-Ning Chen1 1Department of Neurology, Cerebrovascular Disease Research Institute, Southwest Hospital, 2Department of Anatomy, Key Laboratory for Biomechanics of Chongqing, Third Military Medical University, Chongqing, People’s Republic of China Background: Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model.Materials and methods: The pCDNA3.1EHA20 was firmly attached onto stents that had been collagen coated and treated with N-succinimidyl-3-(2-pyridyldithiolpropionate solution and anti-DNA immunoglobulin fixation. Anti-restenosis effects of modified vs control (the bare-metal stent and pCDNA3.1 void vector stents were assessed by Western blot and scanning electron microscopy, as well as by morphological and inflammatory reaction analyses.Results: Stent-delivered A20 gene was locally expressed in porcine carotids in association with significantly greater extent of re-endothelialization at day 14 and of neointimal hyperplasia inhibition at 3 months than stenting without A20 gene expression.Conclusion: The A20-gene-eluting stent inhibits neointimal hyperplasia while promoting re-endothelialization and therefore constitutes a novel potential alternative to prevent restenosis while minimizing complications. Keywords: restenosis, A20, gene therapy, stent, endothelialization

  19. A porcine model: surgical anatomy of the orbit for maxillofacial surgery.

    Science.gov (United States)

    Kyllar, Michal; Štembírek, Jan; Danek, Zdenek; Hodan, Radek; Stránský, Jiří; Machoň, Vladimír; Foltán, René

    2016-04-01

    Due to its similarity to humans, the pig has proven to be a suitable biomodel for both research purposes and for training medical professionals, particularly in surgical specializations. For example, new implant materials have been tested on pig jaws and pigs have also been used in the development of new surgical techniques. For optimizing the effectiveness of such research or training, detailed data on the anatomy of their particular features are needed. At present, however, only limited information related to surgical and imaging anatomy of the facial and orbital areas of the pig and its comparison to human structures from the experimental surgery point of view is available in the literature. The aim of this study was to obtain such data and to compare the morphological structures of the porcine and human orbital regions and to lay down the foundation for practical use in experimental surgery. Ten pig heads were examined using computed tomography (CT) and magnetic resonance imaging (MRI) and, subsequently, a dissection of the orbit was carried out. Attention was focused on the structure of the orbit (floor, rim and nerves) frequently affected by pathological processes in humans (such as trauma, infection or tumours) and which consequently are frequently the subject of maxillofacial surgery. The porcine orbit is suitable for use in experimental medicine. However, if used in experiments, its anatomical peculiarities must be taken into consideration. Our study presents a foundation of basic knowledge for researchers who plan to use the pig as a biomedical model to investigate alternative treatments in the head region.

  20. Fasciotomy Reduces Compartment Pressures and Improves Recovery in a Porcine Model of Extremity Vascular Injury and Ischemia/Reperfusion

    Science.gov (United States)

    2012-10-01

    Forty female yorkshire (75 ± 5kg) swine (Sus Scrofa ; Midwest Research Swine, 31009 645 th Ave., Gibbon, MN 55335) were housed 7 days prior to the...Burkhardt GE, Spencer JR, Gifford SM, Propper B, Jones L, Sumner N, et al. A large animal survival model (Sus scrofa ) of extremity ischemia/reperfusion and...Williams K, Jones L, et al. The impact of ischemic intervals on neuromuscular recovery in a porcine (Sus scrofa ) survival model of extremity vascular

  1. Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

    Directory of Open Access Journals (Sweden)

    Kaiser Carmen

    2010-07-01

    Full Text Available Abstract Background Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. Results Infected cultures were investigated by immunofluorescence (IF, transmission electron microscopy (TEM and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs, medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. Conclusions In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.

  2. Development of an ex vivo human-porcine respiratory model for preclinical studies.

    Science.gov (United States)

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M

    2017-02-24

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures "pleural" depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with (81m)Krypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.

  3. Development of an ex vivo human-porcine respiratory model for preclinical studies

    Science.gov (United States)

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M.

    2017-01-01

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures “pleural” depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies. PMID:28233793

  4. Endovascular Broad-Neck Aneurysm Creation in a Porcine Model Using a Vascular Plug

    Energy Technology Data Exchange (ETDEWEB)

    Muehlenbruch, Georg, E-mail: gmuehlenbruch@ukaachen.de; Nikoubashman, Omid; Steffen, Bjoern; Dadak, Mete [RWTH Aachen University, Department of Diagnostic and Interventional Neuroradiology, University Hospital (Germany); Palmowski, Moritz [RWTH Aachen University, Department of Nuclear Medicine, University Hospital (Germany); Wiesmann, Martin [RWTH Aachen University, Department of Diagnostic and Interventional Neuroradiology, University Hospital (Germany)

    2013-02-15

    Ruptured cerebral arterial aneurysms require prompt treatment by either surgical clipping or endovascular coiling. Training for these sophisticated endovascular procedures is essential and ideally performed in animals before their use in humans. Simulators and established animal models have shown drawbacks with respect to degree of reality, size of the animal model and aneurysm, or time and effort needed for aneurysm creation. We therefore aimed to establish a realistic and readily available aneurysm model. Five anticoagulated domestic pigs underwent endovascular intervention through right femoral access. A total of 12 broad-neck aneurysms were created in the carotid, subclavian, and renal arteries using the Amplatzer vascular plug. With dedicated vessel selection, cubic, tubular, and side-branch aneurysms could be created. Three of the 12 implanted occluders, two of them implanted over a side branch of the main vessel, did not induce complete vessel occlusion. However, all aneurysms remained free of intraluminal thrombus formation and were available for embolization training during a surveillance period of 6 h. Two aneurysms underwent successful exemplary treatment: one was stent-assisted, and one was performed with conventional endovascular coil embolization. The new porcine aneurysm model proved to be a straightforward approach that offers a wide range of training and scientific applications that might help further improve endovascular coil embolization therapy in patients with cerebral aneurysms.

  5. Transgastric endoscopic gastrojejunostomy using holing followed by interrupted suture technique in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Su-Yu; Chen; Hong; Shi; Sheng-Jun; Jiang; Yong-Guang; Wang; Kai; Lin; Zhao-Fei; Xie; Xiao-Jing; Liu

    2015-01-01

    AIM: To demonstrate the feasibility and reproducibility of a pure natural orifice transluminal endoscopic surgery(NOTES) gastrojejunostomy using holing followed by interrupted suture technique using a single endoloop matched with a pair of clips in a non-survival porcine model.METHODS: NOTES gastrojejunostomy was performed on three female domestic pigs as follows: Gastrostomy, selection and retrieval of a free-floating loop of the small bowel into the stomach pouch, hold and exposure of the loop in the gastric cavity using a submucosal inflation technique, execution of a gastro-jejunal mucosal-seromuscular layer approximation using holing followed by interrupted suture technique with endoloop/clips, and full-thickness incision of the loop with a Dual knife.RESULTS: Pure NOTES side-to-side gastrojejunostomy was successfully performed in all three animals. No leakage was identified via methylene blue evaluation following surgery.CONCLUSION: This novel technique for preforming a gastrointestinal anastomosis exclusively by NOTES is technically feasible and reproducible in an animal model but warrants further improvement.

  6. Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

    Science.gov (United States)

    Shen, Yu-I; Song, Hyun-Ho G; Papa, Arianne E; Burke, Jacqueline A; Volk, Susan W; Gerecht, Sharon

    2015-10-01

    Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.

  7. Towards the establishment of a porcine model to study human amebiasis.

    Directory of Open Access Journals (Sweden)

    Fabienne Girard-Misguich

    Full Text Available BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i the trophozoite, growing in the intestine and (ii the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development.

  8. Towards the Establishment of a Porcine Model to Study Human Amebiasis

    Science.gov (United States)

    Girard-Misguich, Fabienne; Cognie, Juliette; Delgado-Ortega, Mario; Berthon, Patricia; Rossignol, Christelle; Larcher, Thibaut; Melo, Sandrine; Bruel, Timothée; Guibon, Roseline; Chérel, Yan; Sarradin, Pierre; Salmon, Henri; Guillén, Nancy; Meurens, François

    2011-01-01

    Background Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. Methodology/Principal Findings We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. Conclusions The pig model could help with simultaneously studying intestinal and extraintestinal lesion development. PMID:22205970

  9. Hypothermia ameliorates gastrointestinal ischemic injury sustained in a porcine cardiac arrest model

    Institute of Scientific and Technical Information of China (English)

    LU Yi; WANG Shuo; LI Chun-sheng

    2012-01-01

    Background During cardiac arrest,the gastrointestinal tract is sensitive to ischemia.Protection of the gastrointestinal tract is a critical factor in determining prognosis following cardiopulmonary resuscitation (CPR).This study seeks to determine the extent of gastrointestinal tract injury and the potential protective effect of inducing hypothermia following a porcine cardiac arrest model and CPR.Methods Ventricular fibrillation was induced by programmed electrical stimulation in 16 male domestic pigs (n=8 per group).Four minutes after ventricular fibrillation,CPR was performed.Pigs that successfully restored spontaneous circulation then received intravenous infusions of saline at either 4C or room temperature to produce hypothermic and control conditions respectively.Serum diamine oxidase and gastrointestinal adenosine triphosphate enzyme activity were determined and histopathology of the gastrointestinal tract was performed by light microscopy and electron microscopy.Results Significant injury of the gastrointestinal tract after CPR was found.Na+-K+ and Ca2+ adenosine triphosphate enzyme activity in the gastric tissue were significantly high in animals receiving hypothermia treatment compared to controls.Hypothermia also significantly reduced serum diamine oxidase after CPR compared to the control group.Moreover,severe injury sustained by the gastrointestinal tissue was significantly ameliorated under hypothermic conditions compared to controls.Conclusions Gastrointestinal injury and abnormal energy metabolism are strikingly evident following CPR.Hypothermia,which is induced by an infusion of 4C saline,can rapidly reduce internal body temperature,improve energy metabolism,and ameliorate injury to the gastrointestinal mucosa after CPR.

  10. In vivo microscopy in a porcine model of acute lung injury.

    Science.gov (United States)

    Bickenbach, Johannes; Czaplik, Michael; Dembinski, Rolf; Pelosi, Paolo; Schroeder, Wolfgang; Marx, Gernot; Rossaint, Rolf

    2010-07-31

    Regional inhomogeneity and alveolar mechanics in a porcine model of acute lung injury (ALI) was evaluated using confocal laser scanning microscopy (CLSM). CLSM was performed through thoracic windows of the upper and lower lobes. Image quantification was conducted by use of a volume air index (VAI). Twelve anesthetized, mechanically ventilated pigs were randomized to non-injury (control group, n = 6) or ALI induced by surfactant depletion (ALI group, n = 6). CLSM was performed at baseline, after 1 h at 5 mbar and after 2 h at 15 mbar positive end-expiratory pressure (PEEP). Haemodynamics, respiratory mechanics and calculation of pulmonary ventilation-perfusion distribution by MIGET were determined. At baseline, VAI was not different. In the upper lobes, VAI significantly decreased in ALI compared to control group, with no changes after PEEP application. In the lower lobes, VAI significantly decreased in ALI compared to control group. Incremental PEEP significantly increased VAI in ALI, but not in control group. Haemodynamics were significantly compromised in the ALI group. A significant deterioration in oxygenation and ventilation-perfusion distribution could be seen being restored after PEEP adjustment. The VAI may help to assess regional inhomogeneity of the acutely injured lung.

  11. Comparison of a new stent and Wallstent for transjugular intrahepatic portosystemic shunt in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Gao Jun Teng; Michael A. Bettmann; P. Jack Hoopes; Li Yang

    2001-01-01

    AIM To evaluate a new balloon-expandablestainless steel stent (Cordis stent ) in atransjugular intrahepatic portosystemic shunt(TIPS) porcine model and compared withWallstent.METHODS TIPS was performed in 26 normaldomestic pigs weighing 20 kg-30 kg using aCordis stent or Wallstent (13 pigs in each stent).All pigs were sacrificed at the 14th day afterTIPS. The stent deployment delivery system,stent patency, and stent recoil after placementwere evaluated. Proliferative response inrepresentative histological sections from thecenter, hepatic and portal regions of the twostent designs were quantified.RESULTS The shunt was widely patent in 4pigs in the Cordis stent group (4/12, prematuredead in 1 pig), and in 5 pigs in the Wallstentgroup (5/13). All remaining stents of bothdesigns were occluded or stenotic. The meanquantified proliferation including thickness ofthe proliferation and the ratio of proliferation:total area in three assayed regions in Cordisstent and Wallstent was 2.18 mm:2.00 mm, and59.18 mm2: 51.66 mm2, respectively (P >0.05).The delivery system and mechanical propertiesof the Cordis stent fuctioned well.CONCLUSION The new Cordis stent isappropriate for TIPS procedure.

  12. Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model.

    Science.gov (United States)

    Niu, Lizhi; Li, Jialiang; Zeng, Jianying; Zhou, Liang; Wang, Song; Zhou, Xulong; Sheng, Lin; Chen, Jibing; Xu, Kecheng

    2014-04-01

    We compared imaging and pathological changes between argon-helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.

  13. Evaluation of ECHO PS Positioning System in a Porcine Model of Simulated Laparoscopic Ventral Hernia Repair.

    Science.gov (United States)

    Hanna, Erin M; Voeller, Guy R; Roth, J Scott; Scott, Jeffrey R; Gagne, Darcy H; Iannitti, David A

    2013-01-01

    Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and (2) Ventralight ST Mesh + transfascial sutures (TSs). Procedure time and mesh centering accuracy overtop of a simulated surgical defect were evaluated. Results. Echo PS demonstrated a 38.9% reduction in the overall procedure time, as compared to TS. During mesh preparation and positioning, Echo PS demonstrated a 60.5% reduction in procedure time (P Echo PS (16.2%), this was not significantly different than TS. Conclusions. Echo PS demonstrated a significant reduction in overall simulated LVHR procedure time, particularly during mesh preparation/positioning. These operative time savings may translate into reduced operating room costs and improved surgeon/operating room efficiency.

  14. Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers.

    Science.gov (United States)

    Grosse-Siestrup, Christian; Unger, Volker; Pfeffer, Jeanette; Dinh, Q Thai; Nagel, Stefan; Springer, Jochen; Witt, Christian; Wussow, Anke; Groneberg, David A

    2004-12-01

    Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with 3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.

  15. Dynamic CT myocardial perfusion imaging: detection of ischemia in a porcine model with FFR verification

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.

  16. In vivo perfusion assessment of an anastomosis surgery on porcine intestinal model (Conference Presentation)

    Science.gov (United States)

    Le, Hanh N. D.; Opferman, Justin; Decker, Ryan; Cheon, Gyeong W.; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2016-04-01

    Anastomosis, the connection of two structures, is a critical procedure for reconstructive surgery with over 1 million cases/year for visceral indication alone. However, complication rates such as strictures and leakage affect up to 19% of cases for colorectal anastomoses and up to 30% for visceral transplantation anastomoses. Local ischemia plays a critical role in anastomotic complications, making blood perfusion an important indicator for tissue health and predictor for healing following anastomosis. In this work, we apply a real time multispectral imaging technique to monitor impact on tissue perfusion due to varying interrupted suture spacing and suture tensions. Multispectral tissue images at 470, 540, 560, 580, 670 and 760 nm are analyzed in conjunction with an empirical model based on diffuse reflectance process to quantify the hemoglobin oxygen saturation within the suture site. The investigated tissues for anastomoses include porcine small (jejunum and ileum) and large (transverse colon) intestines. Two experiments using interrupted suturing with suture spacing of 1, 2, and 3 mm and tension levels from 0 N to 2.5 N are conducted. Tissue perfusion at 5, 10, 20 and 30 min after suturing are recorded and compared with the initial normal state. The result indicates the contrast between healthy and ischemic tissue areas and assists the determination of suturing spacing and tension. Therefore, the assessment of tissue perfusion will permit the development and intra-surgical monitoring of an optimal suture protocol during anastomosis with less complications and improved functional outcome.

  17. Bioartificial heart: a human-sized porcine model--the way ahead.

    Directory of Open Access Journals (Sweden)

    Alexander Weymann

    Full Text Available BACKGROUND: A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. METHODS: We decellularized porcine hearts (n = 10 by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC under simulated physiological conditions. RESULTS: Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05. Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. CONCLUSIONS: Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure.

  18. Evaluation of the chemical-enzymatic decellularization method for obtaining extracellular trachea matrixes in a porcine model

    Directory of Open Access Journals (Sweden)

    Morales-Valencia, Mariana

    2016-04-01

    Full Text Available Introduction: Different diseases may affect the trachea and, therefore, the quality of life. Tissue engineering may be a therapeutic alternative for patients with such diseases, using decellularized trachea matrixes seeded with cells from the recipient, which do not generate immune response and may even prevent rejection of zoo-transplants. Objective: To evaluate a decellularization method to obtain tracheal extracellular matrixes in the porcine model. Materials and methods: Two study groups, treated and control, were obtained from 5 porcine tracheas. A chemical-enzymatic method for decellularization was used. Histological analyses were performed with hematoxylin-eosin, Masson’s trichromic stain and safranin O. Biomechanical properties of both groups were evaluated by determining the Young modulus, maximum strength and deformation rate. Results: Compared to the controls, there was a 66 % decrease in the cell content in the treated specimens. Collagen was preserved and a reduction of glycosaminoglycans was detected. Biomechanical tests revealed a significant difference in the percentage of deformation, with no alteration of the remaining parameters. Conclusions: The evaluated decellularization method proved to be efficient to reduce the cellular content of porcine tracheas, with a considerable decrease in cost and production time. These advantages could make it a good option for the socio-economic Colombian conditions.

  19. The chronic diseases modelling approach

    NARCIS (Netherlands)

    Hoogenveen RT; Hollander AEM de; Genugten MLL van; CCM

    1998-01-01

    A mathematical model structure is described that can be used to simulate the changes of the Dutch public health state over time. The model is based on the concept of demographic and epidemiologic processes (events) and is mathematically based on the lifetable method. The population is divided over s

  20. Investigation of long-term implantation of BuMA stent in a porcine coronary model

    Institute of Scientific and Technical Information of China (English)

    CHEN Ming; WANG Xin-gang; ZHENG Bo; PENG Hong-yu; Zhang Xiao-yan; ZHANG Bin; HUO Yong

    2012-01-01

    Background Stent-based delivery of sirolimus has been shown to reduce neointimal hyperplasia significantly.However,the long-term effect of the polymer is thought to initiate and sustain an inflammatory response and contribute to the occurrence of late complications.Our study aimed to evaluate the efficacy and safety of the BuMA biodegradable drug-coated sirolimus-eluting stent(BSES)for inhibiting neointimal hyperplasia in a porcine coronary model.Methods Four types of stents were implanted at random in different coronary arteries of the same pig:BSES(n=24),bare metal stent(BMS)(n=24),biodegradable polymer coated stent without drug(PCS)(n=24)and only poly(n-butyl methacrylate)base layer coated stent(EGS)(n=23).In total,26 animals underwent successful random placement of 95 oversized stents in the coronary arteries.Coronary angiography was performed after 28 days,90 days and 240 days of stent implantation.After 14 days,28 days,90 days and 240 days,6 animals at each timepoint were sacrificed for histomorphologic analysis.Results The 28-day,90-day and 240-day results of quantitative coronary angiography(QCA)showed reduction in luminal loss(LL)in the BSES group when compared with the BMS group;(0.20±0.35)mm vs.(0.82±0.51)mm(P=0.035),(0.20±0.30)mm vs.(0.93±0.51)mm(P=0.013),and(0.18±0.16)mm vs.(0.19±0.24)mm(P=0.889),respectively.By 28-day,90-day and 240-day histomorphomeric analysis results,there was also a corresponding significant reduction in neointimal tissue proliferation with similar injury scores of BSES compared with the BMS control;average neointimal area(0.90±0.49)mm2 vs.(2.16±1.29)mm2(P=0.049),(1.53±0.84)mm2 vs.(3.41±1.55)mm2(P=0.026),and(2.43±0.95)mm2 vs.(3.12±1.16)mm2(P=0.228),respectively.High magnification histomorphologic examination revealed similar inflammation scores and endothelialization scores in both the BSES and BMS groups.Conclusions The BuMA biodegradable drug-coated sirolimus-eluting stents can significantly reduce neointimal

  1. A model study on color and related structural properties of cured porcine batters.

    NARCIS (Netherlands)

    Palombo, R.

    1990-01-01

    Color, determined by tristimulus colorimeters, and related structural properties, i.e., microstructure, surface rheology, and bulk rheology, of cured porcine meat batters were studied.Effects of various processing factors (such as, temperature, air pressure during chopping, and cutter type) on chang

  2. The rolling-circle melting-pot model for porcine circovirus DNA replication

    Science.gov (United States)

    A stem-loop structure, formed by a pair of inverted repeats during DNA replication, is a conserved feature at the origin of DNA replication (Ori) among plant and animal viruses, bacteriophages and plasmids that replicate their genomes via the rolling-circle replication (RCR) mechanism. Porcine circo...

  3. A zebrafish larval model to assess virulence of porcine streptococcus suis strains

    NARCIS (Netherlands)

    Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M.; Baarlen, Van Peter

    2016-01-01

    Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains

  4. Serum-stabilized naked caspase-3 siRNA protects autotransplant kidneys in a porcine model.

    Science.gov (United States)

    Yang, Cheng; Zhao, Tian; Zhao, Zitong; Jia, Yichen; Li, Long; Zhang, Yufang; Song, Mangen; Rong, Ruiming; Xu, Ming; Nicholson, Michael L; Zhu, Tongyu; Yang, Bin

    2014-10-01

    The naked small interfering RNA (siRNA) of caspase-3, a key player in ischemia reperfusion injury, was effective in cold preserved and hemoreperfused kidneys, but not autotransplanted kidneys in our porcine models. Here, chemically modified serum stabilized caspase-3 siRNAs were further evaluated. The left kidney was retrieved and infused by University of Wisconsin solution with/without 0.3 mg caspase-3 or negative siRNA into the renal artery for 24-hour cold storage (CS). After an intravenous injection of 0.9 mg siRNA and right-uninephrectomy, the left kidney was autotransplanted for 2 weeks. The effectiveness of caspase-3 siRNA was confirmed by caspase-3 knockdown in the post-CS and/or post-transplant kidneys with reduced apoptosis and inflammation, while the functional caspase-3 siRNA in vivo was proved by detected caspase-3 mRNA degradation intermediates. HMGB1 protein was also decreased in the post-transplanted kidneys; correlated positively with renal IL-1β mRNA, but negatively with serum IL-10 or IL-4. The minimal off-target effects of caspase-3 siRNA were seen with favorable systemic responses. More importantly, renal function, associated with active caspase-3, HMGB1, apoptosis, inflammation, and tubulointerstitial damage, was improved by caspase-3 siRNA. Taken together, the 2-week autotransplanted kidneys were protected when caspase-3 siRNA administrated locally and systemically, which provides important evidence for future clinical trials.

  5. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Woong, E-mail: cooljay@korea.ac.kr; Lu, David S. K., E-mail: dlu@mednet.ucla.edu; Osuagwu, Ferdnand, E-mail: fosuagwu@mednet.ucla.edu; Raman, Steven, E-mail: sraman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Lassman, Charles, E-mail: classman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Pathology (United States)

    2013-11-07

    PurposeTo evaluate the chronological effects of irreversible electroporation (IRE) on large hilar bile ducts in an in vivo porcine model correlated with computed tomography (CT) cholangiography and histopathology.Materials and MethodsTwelve IRE zones were made along hilar bile ducts intraoperatively under ultrasound (US)-guidance in 11 pigs. Paired electrodes were placed either on opposing sides of the bile duct (straddle [STR]) or both on one side of the bile duct (one-sided [OSD]). The shortest electrode-to-duct distance was classified as periductal (≤2 mm) or nonperiductal (>2 mm). CT cholangiography and laboratory tests were performed before IRE and again at 2 days, 4 weeks, and 8 weeks after IRE. Degree of bile duct injury were graded as follows: grade 0 = no narrowing; grade 1 = ≤50 % duct narrowing; grade 2 = >50 % narrowing without proximal duct dilatation; grade 3 = grade 2 with proximal duct dilatation; and grade 4 = grade 3 with enzyme elevation. Pigs were selected for killing and histopathology at 2 days, 4, and 8 weeks.ResultsNonperiductal electrode placement produced no long-term strictures in 5 of 5 ducts. Periductal electrode placement produced mild narrowing in 6 of 7 ducts: 5 grade 1 and 1 grade 2. None showed increased enzymes. There was no significant difference between STR versus OSD electrode placement. Histopathology showed minor but relatively greater ductal mural changes in narrowed ducts.ConclusionIn the larger hilar ducts, long-term patency and mural integrity appear resistant to IRE damage with the energy deposition used, especially if the electrode is not immediately periductal in position.

  6. Gene expression profiling in porcine maternal infanticide: a model for puerperal psychosis.

    Science.gov (United States)

    Quilter, Claire R; Gilbert, Colin L; Oliver, Gina L; Jafer, Osman; Furlong, Robert A; Blott, Sarah C; Wilson, Anna E; Sargent, Carole A; Mileham, Alan; Affara, Nabeel A

    2008-10-01

    The etiology of mental disorders remains largely unclear. Complex interactions between genetic and environmental factors are key to the development of such disorders. Puerperal psychosis is the most extreme form of postnatal mood disorder in women. Similarly, parturition in the pig can trigger extreme behavioral disturbances, including maternal infanticide. In this study, we have used a targeted cDNA microarray approach using the pig as a model to understand the genes and genetic pathways that are involved in these processes. Two subtracted cDNA libraries from porcine hypothalamus were constructed, which were enriched for genes that were over-expressed and under-expressed in the aberrant behavioral phenotype, compared to the matched control. In addition to this, a normalized library was constructed from hypothalamus and pituitary samples taken from pigs in a variety of reproductive states. The libraries were partially sequenced and combined represented approximately 5,159 different genes. Microarray analysis determined differences in gene expression between hypothalamus samples from nine matched pairs of infanticidal versus control animals, using a common reference design. Microarray analysis of variance (MAANOVA) identified 52 clones as being differentially expressed (P infanticide phenotype, a second analysis with friendly statistics package for microarray analysis (FSPMA) identified 9 genes in common to MAANOVA, and a further 16 genes. A rapid cross-species screen onto a human oligonucleotide array confirmed 3 genes and highlighted 61 more potential candidates. Some of these genes and the pathways in which they are involved were also implicated in a parallel QTL study on maternal infanticide.

  7. A Novel High Nitrogen Nickel-free Coronary Stents System:Evaluation in a Porcine Model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bin; CHEN Ming; ZHENG Bo; WANG Xin Gang; WANG Xi Ting; FAN Yuan Yuan; HUO Yong

    2014-01-01

    Objective To study the safety of the novel high nitrogen nickel-free austenitic stainless steel bare metal stents (BMS) in a recognized porcine coronary model and to select a better grid structure of it. Methods Three types of stents were randomly implanted in different coronary arteries of the same pig: 316L stainless steel BMS (316L-BMS) (n=12), novel high nitrogen nickel-free stents Grid A (NF-A-BMS) (n=12) and novel high nitrogen nickel-free stents Grid B (NF-B-BMS) (n=12). In total, eighteen animals underwent successful random placement of 36 oversized stents in the coronary arteries. Coronary angiography was performed after 36 d of stents implantation. Nine animals were respectively sacrificed after 14 d and 36 d for histomorphologic analysis. Results Quantitative coronary angiography (QCA) showed similar luminal loss (LL) in the three groups:(0.21±0.17) mm for 316L-BMS, (0.16±0.12) mm for NF-A-BMS, (0.24±0.15) mm for NF-B-BMS (P>0.05). Histomorphomeric analysis after 15 d and 36 d revealed that there was also no significant difference among the three groups in neointimal area (NA) with similar injury scores respectively. High magnification histomorphologic examination showed similar inflammation scores in the three groups, but NF-A-BMS group had poorer endothelialization scores compared with NF-B-BMS group, 2.00±0.63 vs. 2.83±0.41 (P=0.015) at 15 d, which also could be proved by the scanning electron microscope. However, the difference could not been observed at 36 d. Conclusion The novel NF-BMS showed similar safety as 316L-BMS during the short-term study. NF-B-BMS had better endothelialization than NF-A-BMS and this may owe to the specific strut units.

  8. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Cirera Salicio, Susanna; Zhernakova, Daria V.

    2014-01-01

    interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model...... in a porcine model. Methods We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes...... in humans and rodents, e.g. CSF1R and MARC2. Conclusions To our knowledge, this is the first study to apply systems biology approaches using porcine adipose tissue RNA-Sequencing data in a genetically characterized porcine model for obesity. We revealed complex networks, pathways, candidate and regulatory...

  9. Early outcome in renal transplantation from large donors to small and size-matched recipients - a porcine experimental model

    DEFF Research Database (Denmark)

    Ravlo, Kristian; Chhoden, Tashi; Søndergaard, Peter

    2012-01-01

    Kidney transplantation from a large donor to a small recipient, as in pediatric transplantation, is associated with an increased risk of thrombosis and DGF. We established a porcine model for renal transplantation from an adult donor to a small or size-matched recipient with a high risk of DGF...... and studied GFR, RPP using MRI, and markers of kidney injury within 10 h after transplantation. After induction of BD, kidneys were removed from ∼63-kg donors and kept in cold storage for ∼22 h until transplanted into small (∼15 kg, n = 8) or size-matched (n = 8) recipients. A reduction in GFR was observed...

  10. Melatonin Does Not Affect Oxidative/Inflammatory Biomarkers in a Closed-Chest Porcine Model of Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Halladin, Natalie L.; Ekelof, Sarah; Jensen, Svend Eggert

    2014-01-01

    Aim: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. Materials and Methods: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion....... There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. Conclusion: Melatonin treatment did not result in reduction of inflammatory...

  11. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trostrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    . An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time...... of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although...

  12. Effect of different resuscitation strategies on post-resuscitation brain damage in a porcine model of prolonged cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Gu Wei; Hou Xiaomin; Li Chunsheng

    2014-01-01

    Background The choice of a defibrillation or a cardiopulmonary resuscitation (CPR)-first strategy in the treatment of prolonged cardiac arrest (CA) is still controversial.The purpose of this study was to compare the effects of defibrillation or CPR administered first on neurological prognostic markers in a porcine model of prolonged CA.Methods After 8 minutes of untreated ventricular fibrillation (VF),24 inbred Chinese Wuzhishan minipigs were randomized to receive either defibrillation first (ID group,n=12) or chest compression first (IC group,n=12).In the ID group,a shock was delivered immediately.If defibrillation failed to attain restoration of spontaneous circulation (ROSC),manual chest compressions were rapidly initiated at a rate of 100 compressions/min and a compression-to-ventilation ratio of 30:2.If VF persisted after five cycles of CPR,a second defibrillation attempt was made.In the IC group,chest compressions were delivered first,followed by a shock.After successful ROSC,hemodynamic status and blood samples were obtained at 0.5,1,2,4,6,and 24 hours after ROSC.Porcine-specific neuron-specific enolase (NSE) and S100B were measured from sera using enzyme-linked immunosorbent assays.Porcine cerebral performance category scores were used to evaluate preliminary neurological function following 24 hours recovery.Surviving pigs were sacrificed at 24 hours after ROSC and brains were removed for electron microscopy analysis.Results The number of shocks,total defibrillation energy,and time to ROSC were significantly lower in the ID group compared with the IC group.Compared with the IC group,S100B expression was decreased at 2 and 4 hours after ROSC,and NSE expression decreased at 6 and 24 hours after ROSC in the ID group.Brain tissue analysis showed that injury was attenuated in the ID group compared with the IC group.There were no significant differences between 6 and 24 hours survival rates.Conclusion Defibrillation first may result in a shorter time to ROSC and

  13. Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model.

    Directory of Open Access Journals (Sweden)

    Young Eun Yoon

    Full Text Available Ischemic preconditioning (IPC is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI. Currently, IPC's mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control, remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe, and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl. Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC.

  14. Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model.

    Science.gov (United States)

    Hacker, Stefan; Mittermayr, Rainer; Nickl, Stefanie; Haider, Thomas; Lebherz-Eichinger, Diana; Beer, Lucian; Mitterbauer, Andreas; Leiss, Harald; Zimmermann, Matthias; Schweiger, Thomas; Keibl, Claudia; Hofbauer, Helmut; Gabriel, Christian; Pavone-Gyöngyösi, Mariann; Redl, Heinz; Tschachler, Erwin; Mildner, Michael; Ankersmit, Hendrik Jan

    2016-04-29

    Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs. Necrotic areas were excised and the wounds were covered with split-thickness mesh skin grafts. Wounds were treated repeatedly with either the secretome of cultured PBMCs (Sec(PBMC)), apoptotic PBMCs (Apo-Sec(PBMC)), or controls. The wounds treated with Apo-Sec(PBMC) had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-Sec(PBMC) had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-Sec(PBMC) significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting.

  15. Scabies mites alter the skin microbiome and promote growth of opportunistic pathogens in a porcine model.

    Directory of Open Access Journals (Sweden)

    Pearl M Swe

    Full Text Available BACKGROUND: The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. METHODOLOGY/PRINCIPAL FINDINGS: In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. CONCLUSIONS

  16. Experimental research of stent anastomosis of gastrojejunostomy in a porcine model

    Institute of Scientific and Technical Information of China (English)

    CAI Xiu-jun; YU Yi-chen; CAI Hua-jie; WANG Yi-fan

    2011-01-01

    Background Gastrojejunostomy is one of the most frequently used procedures for general surgeons. The creation of anastomosis between various parts of the gastrointestinal tract is a basic technical component and major task in the daily practice of almost all gastrointestinal procedures. This research evaluated a new procedure of making gastrointestinal anastomosis with stent.Methods Twenty experimental mini-pigs were randomized into two groups. In stent anastomosis group (SA), the anastomoses were constructed with a poly-levolactic acid stent. In hand-sewn group (HA), the anastomoses were performed with a single-layer continuous suture. Abdominal X-ray with intraluminal contrast was performed on the 10th postoperative day. Five pigs of each group were sacrificed on the postoperative days 3 and 14 to determine anastomotic bursting pressure in situ, hydroxyproline concentration, and histopathological evaluation of the anastomotic sites.Results There was no intraoperative morbidity or mortality. The median time needed for the sutured anastomosis was (21.7±2.3) minutes and for the stent anastomosis was (11.9±1.9) minutes (P <0.001). Abdominal X-ray with intraluminal contrast demonstrated normal gas distribution and showed no evidence of leakage or obstruction. Macroscopic appearance at the longitudinal opening of anastomosis was always good in both groups. The median anastomotic bursting pressure was (18.2±1.6) kPa in SA group on postoperative day 3, compared with (11.7±3.2) kPa in HA group (P=0.003). The anastomotic bursting pressure on day 14 was not significantly different between SA group ((27.1±2.6)kPa) and HA group ((28.3±1.7) kPa) (P=0.388). The hydroxyproline concentrations were not significantly different.Conclusions The stent anastomosis was not considered to be more difficult than a sutured anastomosis. This method is proved to be safe and feasible compared with the traditional hand-sewn method in the porcine model. The method increases early

  17. Computational Biology: Modeling Chronic Renal Allograft Injury.

    Science.gov (United States)

    Stegall, Mark D; Borrows, Richard

    2015-01-01

    New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury.

  18. Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

    Directory of Open Access Journals (Sweden)

    Howie Forbes

    2010-03-01

    Full Text Available Abstract Background The development of effective therapies for acute liver failure (ALF is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein. Control pigs (n = 4 survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg, increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3. Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3 observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02 and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14 coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 μmol/l. Liver histology revealed evidence of severe centrilobular necrosis

  19. Evaluation of lincomycin in drinking water for treatment of induced porcine proliferative enteropathy using a Swine challenge model.

    Science.gov (United States)

    Bradford, James R; Winkelman, Nathan L; Moreira, Frederico P; Elfring, Gregory D

    2004-01-01

    A single-location, challenge-model study was conducted to evaluate the effectiveness of lincomycin against porcine proliferative enteropathy when administered through the drinking water at 125 and 250 mg/gallon. The primary variables of interest were pig removal rate, diarrhea scores, demeanor scores, and abdominal appearance scores. Ancillary performance variables examined included average daily feed intake, average daily gain, and feed per gain. After a 3-day acclimation period, pigs were challenged on 2 consecutive days with a mucosal homogenate containing a total dose of 1.4 x 10(9) cells of Lawsonia intracellularis. Five days later, when porcine proliferative enteropathy was well established, drinking water medicated with 125 mg (L125) or 250 mg (L250) lincomycin/gallon was provided to two groups of pigs for 10 days. Pigs were observed for 13 days following the treatment period. A third group of pigs served as controls and received unmedicated drinking water throughout the study. The L250 group experienced a significantly lower (P < .05) pig removal rate than the control group over the 23-day observation period. Additionally, for every primary variable, the L250 group experienced a significantly decreased (P < .01) number of abnormal days compared with the control group. The L125 group showed a significant reduction (P < .05) in abnormal demeanor and abnormal abdominal appearance scores compared with controls.

  20. Porcine models for the study of local and systemic regulation of innate immune factors in obesity

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard

    Overweight and obesity are increasing at an alarming rate globally, and are quickly becoming one of the largest medical problems in the world. Overweight and obesity are risk factors of metabolic diseases such as diabetes, cardiovascular diseases and cancer. Obesity is associated with a chronic...... state of low-grade inflammation in the adipose tissues, which involves several factors of the innate immune response having a range of systemic effects and which has been implicated in the development of the metabolic syndrome. To investigate the impact of obesity and obesity-related diseases good...... translational animal models are needed, and as such pigs have been proposed as relevant models for human obesity-induced inflammation as pigs share many genetic, anatomical and physiological features with humans. In this project the up- and downregulation of genes and proteins involved in the innate immune...

  1. Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

    DEFF Research Database (Denmark)

    Li, Yiping; Kang, H.N.; Babiuk, L.A.

    2006-01-01

    AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without...

  2. Biopsychosocial model of chronic recurrent pain

    Directory of Open Access Journals (Sweden)

    Zlatka Rakovec-Felser

    2009-07-01

    Full Text Available Pain is not merely a symptom of disease but a complex independent phenomenon where psychological factors are always present (Sternberg, 1973. Especially by chronic, recurrent pain it's more constructive to think of chronic pain as a syndrome that evolves over time, involving a complex interaction of physiological/organic, psychological, and behavioural processes. Study of chronic recurrent functional pain covers tension form of headache. 50 suffering persons were accidentally chosen among those who had been seeking medical help over more than year ago. We tested their pain intensity and duration, extent of subjective experience of accommodation efforts, temperament characteristics, coping strategies, personal traits, the role of pain in intra- and interpersonal communication. At the end we compared this group with control group (without any manifest physical disorders and with analyse of variance (MANOVA. The typical person who suffers and expects medical help is mostly a woman, married, has elementary or secondary education, is about 40. Pain, seems to appear in the phase of stress-induced psychophysical fatigue, by persons with lower constitutional resistance to different influences, greater irritability and number of physiologic correlates of emotional tensions. Because of their ineffective style of coping, it seems they quickly exhausted their adaptation potential too. Through their higher level of social–field dependence, reactions of other persons (doctor, spouse could be important factors of reinforcement and social learning processes. In managing of chronic pain, especially such as tension headache is, it's very important to involve bio-psychosocial model of pain and integrative model of treatment. Intra- and inter-subjective psychological functions of pain must be recognised as soon as possible.

  3. Ischemic etiopathogenesis as the possible origin of post-double baloon enteroscopy pancreatitis: a porcine model study

    Directory of Open Access Journals (Sweden)

    Federico Soria

    2015-01-01

    Full Text Available The aim is to evaluate the pancreatic vascular-ischemic effects related to double balloon enteroscopy in the porcine model as a possible etiopathogenesis of post-enteroscopic pancreatitis. For this reason we carry out two independent experiments in a porcine animal model. In the first arm protocol (group I, 10 animals underwent 90 minutes of oral enteroscopy with 7 days follow-up. The levels of amylase, lipase and C-reactive protein were measured at T0 basal-T1 -90 min, T2-24, T3-7 days. Also we perform upper gastrointestinal endoscopy in a control group. At 7 days, the animals of experimental protocol-I had their pancreases removed for a pathological and immunohistochemical study to evaluate vascular epithelial growth factor (VEGF expression. The second experimental protocol in this study aims to evaluate possible changes in vascular topography due to the double balloon enteroscopy (DBE. Group-II (10 animals underwent oral enteroscopy and selective angiography of the cranial mesenteric artery and celiac trunk. None of the group I or control group animals presented pancreatitis, although the biochemical results for group-I showed increases in the levels of amylase, lipase and C reactive protein at 24 hours. The microscopic study for group-I showed pancreatic necrotic foci and positive VEGF expression, though these changes were not expressed in the control group. These foci were found in 50 % of the group I animals and in relation to the total of the parenchyma were quantified at 6 % of the pancreas. The results for group-II showed that the enteroscopy caused mobilization of the mesenteric vascular axis, with signs of both intestinal and pancreatic hypoperfusion. The conclusions of this study are that, after enteroscopy in the porcine model, pancreatic necrotic foci are produced, in addition to ischemic phenomena causing VEGF expression. This could be related to episodes of visceral hypoperfusion caused by vascular alterations on a topographic

  4. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

    Science.gov (United States)

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up. Methods Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI. Results Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function. Conclusions As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I. PMID:27760220

  5. Models of chronic obstructive pulmonary disease

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    Chung K Fan

    2004-11-01

    Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations.

  6. Development of an in vitro porcine aorta model to study the stability of stent grafts in motor vehicle accidents.

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    Darvish, Kurosh; Shafieian, Mehdi; Romanov, Vasily; Rotella, Vittorio; Salvatore, Michael D; Blebea, John

    2009-04-01

    Endovascular stent grafts for the treatment of thoracic aortic aneurysms have become increasingly utilized and yet their locational stability in moderate chest trauma is unknown. A high speed impact system was developed to study the stability of aortic endovascular stent grafts in vitro. A straight segment of porcine descending aorta with stent graft was constrained in a custom-made transparent urethane casing. The specimen was tested in a novel impact system at an anterior inclination of 45 deg and an average deceleration of 55 G, which represented a frontal automobile crash. Due to the shock of the impact, which was shown to be below the threshold of aortic injury, the stent graft moved 0.6 mm longitudinally. This result was repeatable. The presented experimental model may be helpful in developing future grafts to withstand moderate shocks experienced in motor vehicle accidents or other dynamic loadings of the chest.

  7. Selective Retrograde Venous Revascularization of the Myocardium when PCI or CABG Is Impossible: Investigation in a Porcine Model

    DEFF Research Database (Denmark)

    Møller, Christian H; Nørgaard, Martin A; Gøtze, Jens P

    2008-01-01

    (LIMA) was anastomosed to the left anterior descending coronary vein (LAD vein) in an off-pump procedure. The LAD vein was ligated proximal to the anastomosis. The LAD artery was ligated proximally. The physiological effects were monitored using microdialysis, tissue oxygen tension, blood flow in LIMA...... tension decreased, but with time some recovery was seen. Cardiac troponin T was elevated. Histological analysis showed ischemic changes. In control pigs, microdialysis was performed for 1.5 hours up to LAD artery ligation, after which all pigs died in ventricular fibrillation arrest. No increase......We investigated the possibility of nourishing the myocardium through selective retrograde coronary venous bypass grafting (CVBG) with an off-pump technique and evaluated various methods of monitoring the physiological effects of this procedure. In a porcine model, the left internal mammary artery...

  8. Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Warfvinge, Karin; Scherfig, Erik;

    2009-01-01

    The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure...... (MAP) minus the intraocular pressure (IOP). It was clamped to 0-30 mm Hg by continuous monitoring of MAP and adjustment of the IOP, which was controlled by cannulation of the anterior chamber. Inner retinal function was assessed by induced multifocal electroretinography (mfERG) with comparisons...... of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2h induced significant reductions in the amplitudes...

  9. Decolonisation of MRSA, S. aureus and E. coli by cold-atmospheric plasma using a porcine skin model in vitro.

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    Tim Maisch

    Full Text Available In the last twenty years new antibacterial agents approved by the U.S. FDA decreased whereas in parallel the resistance situation of multi-resistant bacteria increased. Thus, community and nosocomial acquired infections of resistant bacteria led to a decrease in the efficacy of standard therapy, prolonging treatment time and increasing healthcare costs. Therefore, the aim of this work was to demonstrate the applicability of cold atmospheric plasma for decolonisation of Gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA, Methicillin-sensitive Staphylococcus aureus and Gram-negative bacteria (E. coli using an ex vivo pig skin model. Freshly excised skin samples were taken from six month old female pigs (breed: Pietrain. After application of pure bacteria on the surface of the explants these were treated with cold atmospheric plasma for up to 15 min. Two different plasma devices were evaluated. A decolonisation efficacy of 3 log(10 steps was achieved already after 6 min of plasma treatment. Longer plasma treatment times achieved a killing rate of 5 log(10 steps independently from the applied bacteria strains. Histological evaluations of untreated and treated skin areas upon cold atmospheric plasma treatment within 24 h showed no morphological changes as well as no significant degree of necrosis or apoptosis determined by the TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates for the first time that cold atmospheric plasma is able to very efficiently kill bacteria applied to an intact skin surface using an ex vivo porcine skin model. The results emphasize the potential of cold atmospheric plasma as a new possible treatment option for decolonisation of human skin from bacteria in patients in the future without harming the surrounding tissue.

  10. Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow

    Institute of Scientific and Technical Information of China (English)

    Jia-hui LI; Peng YANG; Ai-li LI; Yong WANG; Yuan-nan KE; Xian-lun LI

    2011-01-01

    Abstract:Objective:To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).Methods:Twenty-two male Chinese mini-swines were randomized into three groups:six in a sham-operation group,and eight each in the control and lipo-PGE1 groups.The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h,and then reperfused for 3 h.Lipo-PGE1 (1 pg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group.Hemodynamic data and proinflammatory cytokines were examined before AMI,2 h after occlusion,and 1,2,and 3 h after reperfusion.Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA).Results:Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both).MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05,P<0.01).Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) after myocardial infarction reperfusion (P<0.05 for both).Conclusions:Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow,decreasing NRA and attenuating the inflammatory response.

  11. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury

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    Rector Edward S

    2004-11-01

    Full Text Available Abstract Background Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model. Methods We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury. Results PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry. Conclusions In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.

  12. Evaluation of coronary blood flow velocity during cardiac arrest with circulation maintained through mechanical chest compressions in a porcine model

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    Wagner Henrik

    2011-12-01

    Full Text Available Abstract Background Mechanical chest compressions (CCs have been shown capable of maintaining circulation in humans suffering cardiac arrest for extensive periods of time. Reports have documented a visually normalized coronary blood flow during angiography in such cases (TIMI III flow, but it has never been actually measured. Only indirect measurements of the coronary circulation during cardiac arrest with on-going mechanical CCs have been performed previously through measurement of the coronary perfusion pressure (CPP. In this study our aim was to correlate average peak coronary flow velocity (APV to CPP during mechanical CCs. Methods In a closed chest porcine model, cardiac arrest was established through electrically induced ventricular fibrillation (VF in eleven pigs. After one minute, mechanical chest compressions were initiated and then maintained for 10 minutes upon which the pigs were defibrillated. Measurements of coronary blood flow in the left anterior descending artery were made at baseline and during VF with a catheter based Doppler flow fire measuring APV. Furthermore measurements of central (thoracic venous and arterial pressures were also made in order to calculate the theoretical CPP. Results Average peak coronary flow velocity was significantly higher compared to baseline during mechanical chests compressions and this was observed during the entire period of mechanical chest compressions (12 - 39% above baseline. The APV slowly declined during the 10 min period of mechanical chest compressions, but was still higher than baseline at the end of mechanical chest compressions. CPP was simultaneously maintained at > 20 mmHg during the 10 minute episode of cardiac arrest. Conclusion Our study showed good correlation between CPP and APV which was highly significant, during cardiac arrest with on-going mechanical CCs in a closed chest porcine model. In addition APV was even higher during mechanical CCs compared to baseline. Mechanical

  13. New Radiofrequency Device to Reduce Bleeding after Core Needle Biopsy: Experimental Study in a Porcine Liver Model

    Science.gov (United States)

    Lim, Sanghyeok; Lee, Min Woo; Song, Kyoung Doo; Kang, Tae Wook; Kim, Young-sun; Lim, Hyo Keun

    2017-01-01

    Objective To evaluate the in vivo efficiency of the biopsy tract radiofrequency ablation for hemostasis after core biopsy of the liver in a porcine liver model, including situations with bleeding tendency and a larger (16-gauge) core needle. Materials and Methods A preliminary study was performed using one pig to determine optimal ablation parameters. For the main experiment, four pigs were assigned to different groups according to heparinization use and biopsy needle caliber. In each pig, 14 control (without tract ablation) and 14 experimental (tract ablation) ultrasound-guided core biopsies were performed using either an 18- or 16-gauge needle. Post-biopsy bleeding amounts were measured by soaking up the blood for five minutes. The results were compared using the Mann-Whitney U test. Results The optimal parameters for biopsy tract ablation were determined as a 2-cm active tip electrode set at 40-watt with a tip temperature of 70–80℃. The bleeding amounts in all experimental groups were smaller than those in the controls; however they were significant in the non-heparinized pig biopsied with an 18-gauge needle and in two heparinized pigs (p < 0.001). In the heparinized pigs, the mean blood loss in the experimental group was 3.5% and 13.5% of the controls biopsied with an 18- and 16-gauge needle, respectively. Conclusion Radiofrequency ablation of hepatic core biopsy tract ablation may reduce post-biopsy bleeding even under bleeding tendency and using a larger core needle, according to the result from in vivo porcine model experiments. PMID:28096727

  14. Expression of collagen genes in the cones of skin in the Duroc/Yorkshire porcine model of fibroproliferative scarring.

    Science.gov (United States)

    Zhu, Kathy Q; Carrougher, Gretchen J; Couture, Oliver P; Tuggle, Christopher K; Gibran, Nicole S; Engrav, Loren H

    2008-01-01

    During the past decades there has been minimal improvement in prevention and treatment of hypertrophic scarring. Reasons include the lack of a validated animal model, imprecise techniques to dissect scar into the histologic components, and limited methodology for measurement of gene expression. These problems have been addressed with the Duroc/Yorkshire model of healing, laser capture microdissection, and the Affymetrix Porcine GeneChip. Here we compared collagen gene expression in fibroproliferative healing in the Duroc breed to nonfibroproliferative healing in the Yorkshires. We made shallow and deep dorsal wounds, biopsied at 1, 2, 3, 12, and 20 weeks. We sampled the dermal cones by laser capture microdissection, extracted and amplified the RNA, and hybridized Affymetrix Porcine GeneChips. We also obtained samples of human hypertrophic scar approximately 20 weeks postinjury. Data were normalized and statistical analysis performed with mixed linear regression using the Bioconductor R/maanova package. Genes for further analysis were also restricted with four biologic criteria, including that the 20-week deep Duroc expression match the human samples. Eleven collagen genes and seven collagen types were differentially over expressed in deep Duroc wounds including 1a1, 1a2, 3a1, 4a1, 4a2, 5a1, 5a2, 5a3, 6a3 (transcript variant 5), 14a1 and 15a1. COL7a1 gene was differentially under expressed in deep Duroc wounds. The results suggest that collagens I, III, IV, V, VI, VII, XIV, and XV [corrected] are involved in the process of fibroproliferative scarring. With these clues, we will attempt to construct the regulatory pathway(s) of fibroproliferative healing.

  15. Efficacy of the porcine species in biomedical research

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    Karina eGutierrez

    2015-09-01

    Full Text Available Since domestication, pigs have been used extensively in agriculture and kept as companion animals. More recently they have been used in biomedical research, given they share many physiological and anatomical similarities with humans. Recent technological advances in assisted reproduction, somatic cell cloning, stem cell culture, genome editing and transgenesis now enable the creation of unique porcine models of human diseases. Here we highlight the potential applications and advantages of using pigs, particularly minipigs, as indispensable large animal models in fundamental and clinical research, including the development of therapeutics for inherited and chronic disorders, and cancers.

  16. Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

    Science.gov (United States)

    Holfeld, Johannes; Zimpfer, Daniel; Albrecht-Schgoer, Karin; Stojadinovic, Alexander; Paulus, Patrick; Dumfarth, Julia; Thomas, Anita; Lobenwein, Daniela; Tepeköylü, Can; Rosenhek, Raphael; Schaden, Wolfgang; Kirchmair, Rudolf; Aharinejad, Seyedhossein; Grimm, Michael

    2016-12-01

    Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm(2) ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models.

    Science.gov (United States)

    Tullberg, Cecilia; Larsson, Karin; Carlsson, Nils-Gunnar; Comi, Irene; Scheers, Nathalie; Vegarud, Gerd; Undeland, Ingrid

    2016-03-01

    In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy-trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 μM of MDA, 0.96 μM of HHE, and 1.6 μM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 μM of MDA; 0.16, and 0.026 μM of HHE; 0.23, and 0.005 μM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies.

  18. Intrathoracic Pressure Regulation Improves Cerebral Perfusion and Cerebral Blood Flow in a Porcine Model of Brain Injury.

    Science.gov (United States)

    Metzger, Anja; Rees, Jennifer; Kwon, Young; Matsuura, Timothy; McKnite, Scott; Lurie, Keith G

    2015-08-01

    Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be of clinical value by noninvasively

  19. Wound healing activity of the leaves of Artocarpus heterophyllus Lam. (Moraceae on ex-vivo porcine skin wound healing model

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    K Periyanayagam

    2013-05-01

    Full Text Available ABSTRACT Objective: To prescreen the ex- vivo wound healing activity of flavonoid rich fraction of ethyl acetate extract of the leaves of Artocarpus heterophyllus Lam. Family Moraceae using porcine skin wound healing model (PSWHM along with  phytochemical, XRF, HPTLC analysis. The aim of this present study is to provide pharmacological validation to the traditional claim for wound healing activity of Artocarpus heterophyllus leaves. Method: Total phenolic content by UV spectral methods and ursolic acid content by HPTLC, trace elements by X-ray fluorescence were determined.  The wound healing effect of the ethyl acetate extract of the leaves of A.heterophyllus (EAAH was evaluated using ex- vivo porcine skin wound healing model - a novel organ culture model system for evaluation of drugs in cell-cell junction in the wound healing process. Results: Total phenolic content by UV method, HPTLC determination of ursolic acid content of EAAH was found to be 376.5mg/g GAE, 134mg/g respectively. XRF study showed the presence of calcium (39.4%, potassium (29.6%, magnesium (2.06%, Iron (0.99%, sulphur (1.83%, zinc (0.083%, strontium (0.23%, manganese (0.13% and aluminium (0.005%.   Histopathological evaluation showed all treated wounds were sound with no signs of apoptosis, necrosis or bacterial contamination and no toxicity of the tested concentrations of EAAH of the leaves. Morphology of the wound margins, epidermis and dermis layer were found to be normal. Epidermal migration or keratinocyte migration distances from the edges of each wound were measured, normalized with the PBS control group and expressed as mean%. The result clearly showed EAAH (1.5% promoted statistically significant wound healing effect is comparable to the standard drug Mupirocin. Conclusion: This study indicates that the ethyl acetate extract of the leaves of A.heterophyllus possesses potential wound healing activity on ex-vivo porcine skin wound healing model. Wound healing

  20. Size dependent skin penetration of nanoparticles in murine and porcine dermatitis models.

    Science.gov (United States)

    Try, Céline; Moulari, Brice; Béduneau, Arnaud; Fantini, Oscar; Pin, Didier; Pellequer, Yann; Lamprecht, Alf

    2016-03-01

    A major limitation in the current topical treatment of inflammatory skin diseases is the inability to selectively deliver the drug to the inflammation site. Recently, smart drug delivery systems such as nanocarriers are being investigated to enhance the selective deposition of anti-inflammatory drugs in inflamed areas of the skin to achieve higher therapeutic efficacy with minimal side effects. Of such systems, polymeric nanoparticles are considered very efficient carriers for the topical drug delivery. In the current work, poly(l-lactide-co-glycolide) nanoparticles of nominal sizes of 70nm (NP70) and 300nm (NP300) were studied for their intra-epidermal distribution in murine and pig atopic dermatitis models over time against the respective healthy controls. Confocal laser scanning microscopical examination of skin biopsies was utilized for the qualitative and semi-quantitative analyses of nanoparticles skin deposition and penetration depth. While no skin penetration was found for any of the particles in healthy skin, the accumulation of NP70 was significantly higher than NP300 in inflamed skin (15-fold in mice, 5-fold in pigs). Penetration depth of NP70 decreased over time in mice from 55±3μm to 20±2μm and similar tendencies were observed for the other formulations. In inflamed pig skin, a similar trend was found for the penetration depth (NP70: 46±12μm versus NP300: 23±3μm); however, the NP amount remained constant for the whole analyzed period. Their ability to penetrate specifically into inflamed skin combined with minimal effects on healthy skin underlines small polymeric nanoparticles' potential as selective drug carriers in future treatment of chronic inflammatory skin diseases such as atopic dermatitis.

  1. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model.

    Science.gov (United States)

    Sanzari, Jenine K; Diffenderfer, Eric S; Hagan, Sarah; Billings, Paul C; Gridley, Daila S; Seykora, John T; Kennedy, Ann R; Cengel, Keith A

    2015-07-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed.

  2. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

    Directory of Open Access Journals (Sweden)

    Pouw JJ

    2015-02-01

    Full Text Available Joost J Pouw,1,* Muneer Ahmed,2,* Bauke Anninga,2 Kimberley Schuurman,1 Sarah E Pinder,2 Mieke Van Hemelrijck,3 Quentin A Pankhurst,4,5 Michael Douek,2 Bennie ten Haken1 1MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 2Research Oncology, Division of Cancer Studies, King’s College London, Guy’s Hospital, London, UK; 3Cancer Epidemiology Group, Division of Cancer Studies, King’s College London, London, UK; 4Healthcare Biomagnetics Laboratory, University College London, London, UK; 5Institute of Biomedical Engineering, University College London, London, UK *These authors contributed equally to this work Introduction: Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model.Materials and methods: Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter dH =32 nm; Sienna+®, dH =59 nm; and ferumoxide, dH =111 nm, and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo, iron quantification (vibrating sample magnetometry, and histopathological assessments were performed on all ex vivo nodes.Results: Transcutaneous “hotspots” were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for

  3. Fluid-structure interaction model of aortic valve with porcine-specific collagen fiber alignment in the cusps.

    Science.gov (United States)

    Marom, Gil; Peleg, Mor; Halevi, Rotem; Rosenfeld, Moshe; Raanani, Ehud; Hamdan, Ashraf; Haj-Ali, Rami

    2013-10-01

    Native aortic valve cusps are composed of collagen fibers embedded in their layers. Each valve cusp has its own distinctive fiber alignment with varying orientations and sizes of its fiber bundles. However, prior mechanical behavior models have not been able to account for the valve-specific collagen fiber networks (CFN) or for their differences between the cusps. This study investigates the influence of this asymmetry on the hemodynamics by employing two fully coupled fluid-structure interaction (FSI) models, one with asymmetric-mapped CFN from measurements of porcine valve and the other with simplified-symmetric CFN. The FSI models are based on coupled structural and fluid dynamic solvers. The partitioned solver has nonconformal meshes and the flow is modeled by employing the Eulerian approach. The collagen in the CFNs, the surrounding elastin matrix, and the aortic sinus tissues have hyperelastic mechanical behavior. The coaptation is modeled with a master-slave contact algorithm. A full cardiac cycle is simulated by imposing the same physiological blood pressure at the upstream and downstream boundaries for both models. The mapped case showed highly asymmetric valve kinematics and hemodynamics even though there were only small differences between the opening areas and cardiac outputs of the two cases. The regions with a less dense fiber network are more prone to damage since they are subjected to higher principal stress in the tissues and a higher level of flow shear stress. This asymmetric flow leeward of the valve might damage not only the valve itself but also the ascending aorta.

  4. Porcine intestinal epithelial cell lines as a new in vitro model for studying adherence and pathogenesis of enterotoxigenic Escherichia coli.

    Science.gov (United States)

    Koh, Seung Y; George, Sajan; Brözel, Volker; Moxley, Rodney; Francis, David; Kaushik, Radhey S

    2008-07-27

    Enterotoxigenic Escherichia coli (ETEC) infections result in large economic losses in the swine industry worldwide. The organism causes diarrhea by adhering to and colonizing enterocytes in the small intestines. While much progress has been made in understanding the pathogenesis of ETEC, no homologous intestinal epithelial cultures suitable for studying porcine ETEC pathogenesis have been described prior to this report. In the current study, we investigated the adherence of various porcine ETEC strains to two porcine (IPEC-1 and IPEC-J2) and one human (INT-407) small intestinal epithelial cell lines. Each cell line was assessed for its ability to support the adherence of E. coli expressing fimbrial adhesins K88ab, K88ac, K88ad, K99, F41, 987P, and F18. Wild-type ETEC expressing K88ab, K88ac, and K88ad efficiently bound to both IPEC-1 and IPEC-J2 cells. An ETEC strain expressing both K99 and F41 bound heavily to both porcine cell lines but an E. coli strain expressing only K99 bound very poorly to these cells. E. coli expressing F18 adhesin strongly bound to IPEC-1 cells but did not adhere to IPEC-J2 cells. The E. coli strains G58-1 and 711 which express no fimbrial adhesins and those that express 987P fimbriae failed to bind to either porcine cell line. Only strains B41 and K12:K99 bound in abundance to INT-407 cells. The binding of porcine ETEC to IPEC-J2, IPEC-1 and INT-407 with varying affinities, together with lack of binding of 987P ETEC and non-fimbriated E. coli strains, suggests strain-specific E. coli binding to these cell lines. These findings suggest the potential usefulness of porcine intestinal cell lines for studying ETEC pathogenesis.

  5. Assessment of distribution and evolution of Mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance

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    Abd-Elmoniem Khaled Z

    2012-01-01

    Full Text Available Abstract Background We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI, in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV remodeling and increased mortality. Methods Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR were performed pre-MI, 9 ± 2 days (early post-MI, and 33 ± 10 days (late post-MI post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC. Electro-anatomic mapping (EAM was performed within 24 hrs of CMR and prior to sacrifice. Results Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early and -17 ± 2.7% (late, p Conclusions Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

  6. Pharmacological Relaxation of the Ureter When Using Ureteral Access Sheaths during Ureterorenoscopy: A Randomized Feasibility Study in a Porcine Model

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    Søren Kissow Lildal

    2016-01-01

    Full Text Available Objective. High intraluminal pressure during ureterorenoscopy (URS increases risk of infectious and haemorrhagic complications. Intrarenal pressure may be reduced by the use of ureteral access sheaths (UASs, which on the other hand may cause ureteral damage. We have previously shown that the β-agonist isoproterenol (ISO, when administered topically in the irrigation fluid, is able to inhibit ureteral muscle tone and lower intrarenal pressure during URS. The aim of this study was to examine the effect of ISO on the success rate of UAS insertion in a porcine model. Materials and Methods. 22 pigs in which a UAS could not initially be placed were randomized to endoluminal irrigation with either ISO (0.1 μg/mL or saline before a new insertion trial. Subsequently, it was registered whether the UAS could be passed without resistance. During extraction of the sheath, any ureteral lesions were characterized ureteroscopically using the PULS classification system. Surgeons were blinded to randomization. Results. In the ISO group, the observed effect of irrigation was 63% successful UAS insertions, compared to 27% in the saline group. No serious lesions (

  7. Load-distributing band improves ventilation and hemodynamics during resuscitation in a porcine model of prolonged cardiac arrest

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    Wang Shuo

    2012-09-01

    Full Text Available Abstract Background The use of mechanical cardiopulmonary resuscitation (CPR has great potential for the clinical setting. The purpose of present study is to compare the hemodynamics and ventilation during and after the load-distributing band CPR, versus the manual CPR in a porcine model of prolonged cardiac arrest, and to investigate the influence of rescue breathing in different CPR protocols. Methods Sixty-four male pigs (n = 16/group, weighing 30 ± 2 kg, were induced ventricular fibrillation and randomized into four resuscitation groups: continuous load-distributing band CPR without rescue ventilation (C-CPR, load-distributing band 30:2 CPR (A-CPR, load-distributing band CPR with continuous rescue breathing (10/min (V-CPR or manual 30:2 CPR (M-CPR. Respiratory variables and hemodynamics were recorded continuously; blood gas was analyzed. Results Tidal volume produced by compressions in the A-, C- and V-CPR groups were significantly higher compared with the M-CPR group (all p 2 of the A-, C- and V-CPR groups were significantly higher and PaCO2 were significantly lower compared with the M-CPR (both p  Conclusions The load-distributing band CPR significantly improved respiratory parameters during resuscitation by augmenting passive ventilation, and significantly improved coronary perfusion pressure. The volume of ventilation produced by the load-distributing band CPR was adequate to maintain sufficient gas exchange independent of rescue breathing.

  8. Development and application of chronic disease risk prediction models.

    Science.gov (United States)

    Oh, Sun Min; Stefani, Katherine M; Kim, Hyeon Chang

    2014-07-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea.

  9. Bronchiolitis Obliterans Organizing Pneumonia in Swine Associated with Porcine Circovirus Type 2 Infection

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    Ching-Chang Cheng

    2011-01-01

    Full Text Available Bronchiolitis obliterans organizing pneumonia (BOOP is a chronic respiratory disease. Although the pathogenesis of BOOP is still incompletely understood, BOOP is responsive to steroids and has a good prognosis. In our five pigs with chronic postweaning multisystemic wasting syndrome (PMWS, typical BOOP lesions were revealed. All five porcine lungs showed typical intraluminal plugs, and porcine circovirus type 2 (PCV2 was identified. They also exhibited similar pathologic findings such as proliferation of type II pneumocytes and myofibroblasts (MFBs, extracellular collagen matrix (ECM deposition, and fragmentation of elastic fibers. MFBs migration correlative molecules, for instance, gelatinase A, B and osteopontin, appeared strongly in the progressing marginal area of polypoid intraluminal plugs of fibrotic lesion. These molecules colocalized with the active MFBs. Both gelatinase activity and intercellular level of active MFBs were significantly increased (<.05. Porcine chronic bronchopneumonia leads to BOOP and it is associated with PCV2 persistent infection. Swine BOOP demonstrates similar cellular constituents with human BOOP. Perhaps their molecular mechanisms of pathogenesis operate in a similar way. Thus we infer that the swine BOOP can be considered as a potential animal model for human BOOP associated with natural viral infection. Moreover, it is more convenient to obtain samples.

  10. A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection.

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Jungersen, Gregers; Agerholm, Jørgen S

    2015-09-28

    Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system in the perspective of genital Chlamydia infection. The comparison of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, only showing a slight difference in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4(+)/CD8(+) double positive T cells. The genital immune system is also very similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa - predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in Göttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5-5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital Chlamydia infection.

  11. Quantitative analysis of Porcine Reproductive and Respiratory Syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach

    Science.gov (United States)

    Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant viral disease facing the global swine industry. Viremia profiles of PRRS virus challenged pigs reflect the severity and progression of the infection within the host and provide crucial information for subsequen...

  12. Changes of the colonic physiologic functions after colonic anastomosis with a degradable stent in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Liang Xiao; Wang Yifan; He Shilin; Cai Xiujun

    2014-01-01

    Background A new procedure of colonic anastomosis with a degradable stent has already been proven to be simple,feasible,and safe in our porcine model.In this study,we evaluated its impact on the colonic physiologic functions.Methods A total of 20 pigs were assigned randomly to either a stent anastomosis group (SA,n=10) or a conventional anastomosis group (CA,n=10).Colonic anastomosis with a degradable stent was performed in the SA group,and conventional hand-sewn anastomosis was performed in the CA group.Body weight,fecal weight,total colonic transit time,immunohistochemistry staining of interstitial cells of Cajal (ICC),plasma diamine oxidases (DAO) levels,and Western blotting analysis of occludin were evaluated before and after anastomosis.Results No obvious diarrhea or constipation was observed in all pigs.No significant difference in body weight between the groups was detected at any time.Yet,the fecal weight was less in the CA group compared with the SA group on postoperative day (POD) 7.No observable colonic paralysis or retention occurred.For total colonic transit time,there was no significant difference between the two groups at any time or among different time points in the same group.The integrated optical density of ICC showed no significant difference on either POD 14 or 30.The plasma DAO levels were remarkably elevated after surgery,and began to decrease since POD 3.However,there was no significant difference between both two groups in plasma DAO levels at any time either.For both groups,the expression of occludin was not significantly different from their pre-surgery level on either POD 14 or 30.Conclusions According to these results,this procedure with a degradable stent was supposed to be the same as the conventional hand-sewn procedure in their impact on the colonic physiologic functions.

  13. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft.

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    Christi M Terry

    Full Text Available Hemodialysis arteriovenous synthetic grafts (AVG provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study's objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis

  14. Comparison of epinephrine and Shen-Fu injection on resuscitation outcomes in a porcine model of prolonged cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Yin Wenpeng; Guo Zhijun; Li Chunsheng

    2014-01-01

    Background Epinephrine has been used as a first-choice vasopressor drug for cardiac arrest (CA) since 1974.However,the administration of epinephrine is controversial.This study aims to compare the effects of Shen-Fu injection (SFI) and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.Methods Ventricular fibrillation (VF) was electrically induced.After 8 minutes of untreated VF and 2 minutes of chest compressions,24 pigs were randomly divided into 3 groups (n=8 per group):central venous injection of SFI (SFI group),epinephrine (EPI group),or saline solution (SA group).The haemodynamic status and oxygen metabolism parameters,including cardiac output,mean arterial pressure,left ventricular dp/dtmax and negative dp/dtmax,oxygen delivery (DO2),and oxygen consumption (VO2),were calculated.Results SFI shortened the time to restoration of spontaneous circulation (ROSC) and decreased the number of shocks,similar to epinephrine.However,the mean arterial pressure,cardiac output,left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC.VO2 and ERO2 decreased after ROSC and then increased.VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC,while those were lowest in the EPI group among all groups.Conclusions SFI shortened the time to ROSC and decreased the number of shocks,similar to epinephrine.However,SFI improved oxygen metabolism,and produced a better hemodynamic status compared with epinephrine.SFI might be a potentially vasopressor drug for the treatment of CA.

  15. Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model.

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    Haifeng Shi

    Full Text Available To evaluate multi-slice computed tomography (CT perfusion imaging (CTPI for identifying microcirculatory dysfunction in small intestinal ischemia-reperfusion (IR injury in a porcine model.Fifty-two pigs were randomly divided into 4 groups: (1 the IR group (n = 24, where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively; (2 the sham-operated (SO group (n = 20, where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively; (3 the ischemia group (n = 4, where the SMA was separated and clamped for 2 h, without reperfusion, and (4 baseline group (n = 4, an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA and superoxide dismutase (SOD and for histopathological examination.The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia. The blood flow (BF, blood volume (BV, and permeability surface (PS among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion.CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury.

  16. Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model.

    Science.gov (United States)

    Khokhlova, Tatiana D; Wang, Yak-Nam; Simon, Julianna C; Cunitz, Bryan W; Starr, Frank; Paun, Marla; Crum, Lawrence A; Bailey, Michael R; Khokhlova, Vera A

    2014-06-03

    The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.

  17. Directed differentiation into neural lineages and therapeutic potential of porcine embryonic stem cells in rat Parkinson's disease model.

    Science.gov (United States)

    Yang, Jenn-Rong; Liao, Chia-Hsin; Pang, Cheng-Yoong; Huang, Lynn Ling-Huei; Lin, Yu-Ting; Chen, Yi-Ling; Shiue, Yow-Ling; Chen, Lih-Ren

    2010-08-01

    This study was conducted to direct porcine embryonic stem (pES) cells differentiating into neural lineages and to investigate therapeutic potential of GFP-expressing pES (pES/GFP(+)) in the rat model of Parkinson's disease (PD). Directed differentiation of pES into neural lineages was induced by suspension culture in medium containing RA, SHH, and FGF combinations without going through embryoid body formation. A high yield of nestin-expressing neural precursors was found in all treatments on day 2 after the 12-day induction. On day 6 after replating, more than 86.2 and 83.4% of the differentiated cells stained positively for NFL and MAP2, respectively. The expression of TH, ChAT, and GABA specific markers were also observed in these NFL-positive neural cells. The undifferentiated pES/GFP(+) cells and their neuronal differentiation derivatives were transplanted into the Sprague-Dawley (SD) rat's brain, and their survival and development was determined by using live animal fluorescence optical imaging system every 15 days. The results showed that fluorescent signals from the injection site of SD rats' brain could be detected through the experimental period of 3 months. The level of fluorescent signal detected in the treatment group was twofold that of the control group. The results of behavior analysis showed that PD rats exhibited stably decreased asymmetric rotations after transplantation with pES/GFP(+)-derived D18 neuronal progenitors. The dopaminergic differentiation of grafted cells in the brain was further confirmed by immunohistochemical staining with anti-TH, anti-DA, and anti-DAT antibodies. These results suggested that the differentiation approach we developed would direct pES cells to differentiate into neural lineages and benefit the development of novel therapeutics involving stem cell transplantation.

  18. In-vivo measurements of coronary blood flow using 16-slice multidetector spiral computed tomography (MDCT) in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Krug, Kathrin Barbara; Bovenschulte, H. [Klinikum der Koeln Univ. (Germany). Inst. fuer Radiologische Diagnostik; Geissler, H.J. [Klinikum der Koeln Univ. (DE). Klinik und Poliklinik fuer Herz- und Thoraxchirurgie] (and others)

    2009-03-15

    To determine whether CTCA supplemented with CT flow measurements can be used to demonstrate and semiquantitatively evaluate poststenotic coronary blood flow in a porcine model. In 10 thoracotomized pigs, transit time flow meter probes were attached to the aorta and left anterior descending artery (LAD) for real-time blood flow volumetry. A vascular silicone occluder was deployed around the LAD proximal to the probe to create medium-grade (MGS) and high-grade stenoses (HGS). The blood flow was measured by CT without vessel occlusion and distal to the stenoses. Time-density curves were generated from CT data. The curves were evaluated by calculating and cross-plotting the variables ''slope of the density increase'', ''peak density'' and ''slope of the post-peak density decrease'' from the LAD and aortic CT data. The flow in the LAD dropped to 41 % {+-} 9 % (mean {+-} SD) for MGS and 12 % {+-} 6 % for HGS of the baseline. Coronary time-density curves plateaued proportional to luminal narrowing. Unimpaired flow could be differentiated statistically significant from poststenotic flow adjacent to MGS and HGS (p < 0.000 and p < 0.002, respectively). Flow adjacent to MGS and HGS was successfully differentiated for ''slope of the density increase'' and ''slope of the post-peak density decrease'' (p < 0.003 and p < 0.030, respectively). (orig.)

  19. In vivo Gd-DTPA concentration for MR lung perfusion measurements: Assessment with computed tomography in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Puderbach, Michael [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Deutsches Krebsforschungszentrum, Department of Radiology (E010), Heidelberg (Germany); Risse, Frank; Semmler, Wolfhard [German Cancer Research Center, Department of Medical Physics in Radiology, Heidelberg (Germany); Biederer, Juergen [University Hospital Schleswig-Holstein, Department of Diagnostic Radiology, Campus Kiel (Germany); Ley-Zaporozhan, Julia; Ley, Sebastian [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); University Heidelberg, Department of Pediatric Radiology, Heidelberg (Germany); Szabo, Gabor [University Heidelberg, Department of Cardiac Surgery, Heidelberg (Germany); Kauczor, Hans-Ulrich [University of Heidelberg, Department of Radiology, Heidelberg (Germany)

    2008-10-15

    A linear relationship between MR signal and contrast-agent concentration (CAC) of the arterial-input function (AIF) is crucial for MR lung-perfusion quantification. The aim was to determine the in-vivo real maximum CAC of the AIF, using cine CT measurements in a porcine model. A dilution series (Gd-DTPA, 0-20 mM) was examined by clinical time-resolved 3D-GRE MRI and by MDCT in cine CT mode. Using the CT setup, data were acquired in five pigs immediately after the injection of 0.05 mmol and 0.07 mmol/kg BW Gd-DTPA. For phantom measurements, mean signal values were determined using a region-of-interest (ROI) analysis and for animal measurements, a ROI was placed in the pulmonary trunk of the cine CT perfusion data sets. The CT phantom measurements were used to calculate the in-vivo maximum CAC corresponding to the HU values obtained in the pulmonary trunk by the cine CT study. Linearity of the AIF of the CT perfusion measurements was verified using the MR phantom measurement results. MR phantom measurements demonstrated linearity for concentrations of 0-4 mM. CT phantom measurements showed linear relation for the entire CAC range. Comparing in-vivo and in-vitro measurements, three of five CA injections at 0.05 mmol/kg and all 0.07 mmol/kg injections exceeded the range of linearity in MRI. The CA dose for quantification of lung perfusion with time-resolved MR studies must be chosen carefully since even with low doses (0.05 mmol/kg) the CAC may exceed the range of linearity in the AIF. (orig.)

  20. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  1. A Mouse Model of Chronic West Nile Virus Disease

    Science.gov (United States)

    Graham, Jessica B.; Swarts, Jessica L.; Wilkins, Courtney; Thomas, Sunil; Green, Richard; Sekine, Aimee; Voss, Kathleen M.; Mooney, Michael; Choonoo, Gabrielle; Miller, Darla R.; Pardo Manuel de Villena, Fernando; Gale, Michael

    2016-01-01

    Infection with West Nile virus (WNV) leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013)F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans. PMID:27806117

  2. Characterization of the porcine TOR1A gene: The first step towards generation of a pig model for dystonia

    DEFF Research Database (Denmark)

    Henriksen, Carina; Madsen, Lone Bruhn; Bendixen, Christian;

    2009-01-01

    . The TOR1A gene was demonstrated to be localized on porcine chromosome 1. Single nucleotide polymorphism (SNP) analysis revealed several SNPs in the porcine TOR1A gene, both in the coding region and also in the 3′ UTR region. Overexpression of mutant (Δ∆E303-304) porcine TorsinA in neuroblastoma cells...

  3. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    DEFF Research Database (Denmark)

    Kloster, Brian Ozeraitis; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    BackgroundA large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. Methods10 pigs...

  4. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    DEFF Research Database (Denmark)

    Kloster, Brian Ozeraitis; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    BACKGROUND: A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. METHODS: 10...

  5. Disseminated Intravascular Coagulation in a Novel Porcine Model of Severe Staphylococcus aureus Sepsis Fulfills Human Clinical Criteria

    DEFF Research Database (Denmark)

    Soerensen, K. E.; Olsen, H. G.; Skovgaard, Kerstin;

    2013-01-01

    the haemostatic and vascular alterations in a novel porcine model of severe S. aureus sepsis, investigating whether the changes fulfill the human clinical criteria for DIC. Five pigs were inoculated intravenously with S. aureus and two control animals were sham-inoculated. Blood samples were collected...... activation. EC activation was identified by expression of von Willebrand factor in small vessels together with elevated mRNA encoding activated EC markers. Severe haemostatic and vascular changes fulfilling the human criteria for DIC were therefore seen in all infected pigs. A tendency towards uncompensated...

  6. A ferret model of COPD-related chronic bronchitis

    OpenAIRE

    Raju, S. Vamsee; Kim, Hyunki; Byzek, Stephen A.; Tang, Li Ping; Trombley, John E; Jackson, Patricia; Rasmussen, Lawrence; Wells, J. Michael; LIBBY, EMILY FALK; Dohm, Erik; Winter, Lindy; Samuel, Sharon L.; Kurt R. Zinn; Blalock, J. Edwin; Schoeb, Trenton R.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway p...

  7. Establishing a Reproducible Hypertrophic Scar following Thermal Injury: A Porcine Model

    Directory of Open Access Journals (Sweden)

    Scott J. Rapp, MD

    2015-02-01

    Conclusions: Deep partial-thickness thermal injury to the back of domestic swine produces an immature hypertrophic scar by 10 weeks following burn with thickness appearing to coincide with the location along the dorsal axis. With minimal pig to pig variation, we describe our technique to provide a testable immature scar model.

  8. The biomechanical behavior and host response to porcine-derived small intestine submucosa, pericardium and dermal matrix acellular grafts in a rat abdominal defect model.

    Science.gov (United States)

    Zhang, Jian; Wang, Guan Yu; Xiao, Yi Pin; Fan, Lie Ying; Wang, Qiang

    2011-10-01

    Several porcine-derived acellular biologic grafts are increasingly used in abdominal wall reconstruction due to the limitations of synthetic meshes in many clinical situations. However, relatively little is known so far about their comparative mechanical characteristics and performance after defect repair. We therefore investigated three most commonly used porcine-derived acellular biomaterials, small intestine submucosa (P-SIS), pericardium (P-PC) and acellular dermal matrix (P-ADM) immediately after prepared, and their effectiveness, biomechanical and histological characteristics in repairing full-thickness abdominal defect in a rat model. P-PC had the best native performance in the burst strength, tensile strength and ball burst among the three porcine-derived scaffolds. P-SIS showed a significantly higher water vapor transmission in comparison with P-PC or P-ADM. Abdominal wall defects in rats were all satisfied repaired with P-SIS, P-PC or P-ADM. No laxity or fistula was observed in the repaired abdominal wall in the P-SIS group up to 8 weeks after surgery. However, there was a tendency for high postoperative abdominal eventration in the P-ADM and P-PC groups as compared with the P-SIS group. With regard to overall aspects of the postoperative laxity, intra-abdominal adhesion formation, tensile stress, stretchability, and degree of tissue ingrowth in terms of collagen deposition and neovascularization, P-SIS exhibits clear advantages over P-PC as well as P-ADM after large abdominal wall defect reconstruction.

  9. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    DEFF Research Database (Denmark)

    Kloster, Brian Ozeraitis; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    BACKGROUND: A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. METHODS: 10...... ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. RESULTS: In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11...... in group A. The most frequent complication was a neurological deficit in the lower limbs. CONCLUSION: In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved...

  10. Malignant infarction of the middle cerebral artery in a porcine model. A pilot study

    Science.gov (United States)

    Martínez-Valverde, Tamara; Sánchez-Guerrero, Ángela; Campos, Mireia; Esteves, Marielle; Gandara, Dario; Torné, Ramon; Castro, Lidia; Dalmau, Antoni; Tibau, Joan

    2017-01-01

    Background and purpose Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). Methods A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. Results PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 μM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. Conclusions The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies. PMID:28235044

  11. Inhalation therapy with the synthetic TIP-like peptide AP318 attenuates pulmonary inflammation in a porcine sepsis model

    OpenAIRE

    Hartmann, Erik K; Ziebart, Alexander; Thomas, Rainer; Liu, Tanghua; Schad, Arno; Tews, Martha; Moosmann, Bernd; Kamuf, Jens; Duenges, Bastian; Thal, Serge C.; David, Matthias

    2015-01-01

    Background The lectin-like domain of TNF-α can be mimicked by synthetic TIP peptides and represents an innovative pharmacologic option to treat edematous respiratory failure. TIP inhalation was shown to reduce pulmonary edema and improve gas exchange. In addition to its edema resolution effect, TIP peptides may exert some anti-inflammatory properties. The present study therefore investigates the influence of the inhaled TIP peptide AP318 on intrapulmonary inflammatory response in a porcine mo...

  12. Biological Characteristics and Etiological Significance of Porcine Respiratory Coronavirus(PRCV)

    Institute of Scientific and Technical Information of China (English)

    FAN Xiuping; FENG Li; SHI Hongyan; CHEN Jianfei

    2009-01-01

    Porcine respiratory coronavirus (PRCV), a spike (S) gene natural deletion mutant of transmissible gastroenteritis virus (TGEV), causes porcine respiratory disease complex. Research advances on porcine respiratory coronavirus were reviewed from four aspects of biological character, the model function for SARS-CoV research, contribution of the immunity to PRCV to protection against TGEV challenge exposure and other etiological significance.

  13. A novel, comprehensive, and reproducible porcine model for determining the timing of bruises in forensic pathology

    DEFF Research Database (Denmark)

    Barington, Kristiane; Jensen, Henrik Elvang

    2016-01-01

    Purpose Calculating the timing of bruises is crucial in forensic pathology but is a challenging discipline in both human and veterinary medicine. A mechanical device for inflicting bruises in pigs was developed and validated, and the pathological reactions in the bruises were studied over time......-dependent response. Combining these parameters, bruises could be grouped as being either less than 4 h old or between 4 and 10 h of age. Gross lesions and changes in the epidermis and dermis were inconclusive with respect to time determination. Conclusions The model was reproducible and resembled forensic cases...

  14. Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Konstantinos J Dabos; Henry R Whalen; Philip N Newsome; John A Parkinson; Neil C Henderson; Ian H Sadler; Peter C Hayes; John N Plevris

    2011-01-01

    AIM: To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF). METHODS: Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and were maintained under anaesthesia only. Using 1H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples. RESULTS: No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only. If we look at the ALF animals, we observed a statistically significant rise of lactate (P < 0.003) and pyruvate (P < 0.018) at the end of the experiments. We also observed statistically significant rises in the concentrations of alanine (P < 0.002), glycine (P < 0.005), threonine (P < 0.048), tyrosine (P < 0.000), phenylalanine (P < 0.000) and isoleucine (P < 0.01). Valine levels decreased significantly (P < 0.05). CONCLUSION: Our pig model of ALF is characterized by an altered gluconeogenetic capacity, an impaired tricarboxylic acid (TCA) cycle and a glycolytic state.

  15. Mesenchymal Stem Cell-Derived Exosomes: Immunomodulatory Evaluation in an Antigen-Induced Synovitis Porcine Model

    Science.gov (United States)

    Casado, Javier G.; Blázquez, Rebeca; Vela, Francisco Javier; Álvarez, Verónica; Tarazona, Raquel; Sánchez-Margallo, Francisco Miguel

    2017-01-01

    Synovitis is an inflammatory process associated with pain, disability, and discomfort, which is usually treated with anti-inflammatory drugs or biological agents. Mesenchymal stem cells (MSCs) have been also successfully used in the treatment of inflammatory-related diseases such as synovitis or arthritis. In the last years, the exosomes derived from MSCs have become a promising tool for the treatment of inflammatory-related diseases and their therapeutic effect is thought to be mediated (at least in part) by their immunomodulatory potential. In this work, we aimed to evaluate the anti-inflammatory effect of these exosomes in an antigen-induced synovitis animal model. To our knowledge, this is the first report where exosomes derived from MSCs have been evaluated in an animal model of synovitis. Our results demonstrated a decrease of synovial lymphocytes together with a downregulation of TNF-α transcripts in those exosome-treated joints. These results support the immunomodulatory effect of these exosomes and point out that they may represent a promising therapeutic option for the treatment of synovitis.

  16. Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model.

    Directory of Open Access Journals (Sweden)

    Zongyang Sun

    Full Text Available PURPOSE: Bone regeneration through distraction osteogenesis (DO is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. MATERIALS AND METHODS: Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs; enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. RESULTS: From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4-5.8×10(7 autologous BM-MSCs (undifferentiated or differentiated were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds

  17. Dynamic myocardial perfusion in a porcine balloon-induced ischemia model using a prototype spectral detector CT

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Fares, Anas; Levi, Jacob; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR ratio (CNRf ) between LAD ischemic and remote healthy

  18. The impact of force on the timing of bruises evaluated in a porcine model

    DEFF Research Database (Denmark)

    Barington, Kristiane; Jensen, Henrik Elvang

    2016-01-01

    In animal models developed in order to estimate the age of bruises, focus has been on the changes over time and not considering the force used to inflict the trauma. In the present study, gross and histological changes in 2, 4, 6 and 8 h old bruises which were inflicted with a low, moderate...... and high force were compared. Twelve experimental pigs were randomly assigned to three groups of force (low, moderate and high force). All pigs were anesthetized, and on each animal four blunt traumas were inflicted on the back with the low, moderate or high force according to the groups. The pigs were...... with the highest force. Therefore, when evaluating forensic cases of bruises in both human and veterinary pathology the impact of force and not only the timing should be taken into consideration...

  19. Non-contrast-enhanced MRA of renal artery stenosis: validation against DSA in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Bley, T.A. [University of Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); University of Wisconsin, Department of Radiology, Madison, WI (United States); Francois, C.J.; Schiebler, M.L. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Wieben, O.; Del Rio, A.M.; Grist, T.M. [University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Takei, N. [GE Healthcare, MR Applied Sciences Laboratory, Tokyo (Japan); Brittain, J.H. [University of Wisconsin, Department of Radiology, Madison, WI (United States); GE Healthcare, MR Applied Sciences Laboratory, Madison, WI (United States); Reeder, S.B. [University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin, Department of Medicine, Madison, WI (United States); University of Wisconsin, Department of Emergency Medicine, Madison, WI (United States)

    2016-02-15

    To compare 3D-inversion-recovery balanced steady-state free precession (IR-bSSFP) non-contrast-enhanced magnetic resonance angiography (MRA) with 3D-contrast-enhanced MRA (CE-MRA) for assessment of renal artery stenosis (RAS) using digital subtraction angiography (DSA) as the reference standard. Bilateral RAS were surgically created in 12 swine. IR-bSSFP and CE-MRA were acquired at 1.5 T and compared to rotational DSA. Three experienced cardiovascular radiologists evaluated the IR-bSSFP and CE-MRA studies independently. Linear regression models were used to calibrate and assess the accuracy of IR-bSSFP and CE-MRA, separately, against DSA. The coefficient of determination and Cohen's kappa coefficient were also generated. Calibration of the three readers' RAS grading revealed R{sup 2} values of 0.52, 0.37 and 0.59 for NCE-MRA and 0.48, 0.53 and 0.71 for CE-MRA. Inter-rater agreement demonstrated Cohen's kappa values ranging from 0.25 to 0.65. Distal renal artery branch vessels were visible to a significantly higher degree with NCE-MRA compared to CE-MRA (p < 0.001). Image quality was rated excellent for both sequences, although image noise was higher with CE-MRA (p < 0.05). In no cases did noise interfere with image interpretation. In a well-controlled animal model of surgically induced RAS, IR-bSSFP based NCE-MRA and CE-MRA accurately graded RAS with a tendency for stenosis overestimation, compared to DSA. (orig.)

  20. Mechanical Intestinal Obstruction in a Porcine Model: Effects of Intra-Abdominal Hypertension. A Preliminary Study.

    Directory of Open Access Journals (Sweden)

    L Correa-Martín

    Full Text Available Mechanical intestinal obstruction is a disorder associated with intra-abdominal hypertension and abdominal compartment syndrome. As the large intestine intraluminal and intra-abdominal pressures are increased, so the patient's risk for intestinal ischaemia. Previous studies have focused on hypoperfusion and bacterial translocation without considering the concomitant effect of intra-abdominal hypertension. The objective of this study was to design and evaluate a mechanical intestinal obstruction model in pigs similar to the human pathophysiology.Fifteen pigs were divided into three groups: a control group (n = 5 and two groups of 5 pigs with intra-abdominal hypertension induced by mechanical intestinal obstruction. The intra-abdominal pressures of 20 mmHg were maintained for 2 and 5 hours respectively. Hemodynamic, respiratory and gastric intramucosal pH values, as well as blood tests were recorded every 30 min.Significant differences between the control and mechanical intestinal obstruction groups were noted. The mean arterial pressure, cardiac index, dynamic pulmonary compliance and abdominal perfusion pressure decreased. The systemic vascular resistance index, central venous pressure, pulse pressure variation, airway resistance and lactate increased within 2 hours from starting intra-abdominal hypertension (p<0.05. In addition, we observed increased values for the peak and plateau airway pressures, and low values of gastric intramucosal pH in the mechanical intestinal obstruction groups that were significant after 3 hours.The mechanical intestinal obstruction model appears to adequately simulate the pathophysiology of intestinal obstruction that occurs in humans. Monitoring abdominal perfusion pressure, dynamic pulmonary compliance, gastric intramucosal pH and lactate values may provide insight in predicting the effects on endorgan function in patients with mechanical intestinal obstruction.

  1. A chronic ulcerative colitis model in rats

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Zhen Qiang Gao; Shu Xian Wang

    2000-01-01

    @@ INTRODUCTION In recent years, there have been many reports about animal model to investigate drugs for inflammatory bowel diseases (IBD). The experimental animal model often used is acetic acid-induced damage of colonic muscosa. In the present study, this animal model was investigated by administering various concentrations of TNBS.

  2. Feasibility of a porcine oral mucosa equivalent: a preclinical study.

    Science.gov (United States)

    Kinikoglu, Beste; Hemar, Julie; Hasirci, Vasif; Breton, Pierre; Damour, Odile

    2012-08-01

    Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell-based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non-keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts.

  3. Hepatic differentiation of porcine embryonic stem cells for translational research of hepatocyte transplantation.

    Science.gov (United States)

    Park, K M; Hussein, K H; Ghim, J H; Ahn, C; Cha, S H; Lee, G S; Hong, S H; Yang, S; Woo, H M

    2015-04-01

    Porcine embryonic stem cells (ES) are considered attractive preclinical research tools for human liver diseases. Although several studies previously reported generation of porcine ES, none of these studies has described hepatic differentiation from porcine ES. The aim of this study was to generate hepatocytes from porcine ES and analyze their characteristics. We optimized conditions for definitive endoderm induction and developed a 4-step hepatic differentiation protocol. A brief serum-free condition with activin A efficiently induced definitive endoderm differentiation from porcine ES. The porcine ES-derived hepatocyte-like cells highly expressed hepatic markers including albumin and α-fetoprotein, and displayed liver characteristics such as glycogen storage, lipid production, and low-density lipoprotein uptake. For the first time, we describe a highly efficient protocol for hepatic differentiation from porcine ES. Our findings provide valuable information for translational liver research using porcine models, including hepatic regeneration and transplant studies, drug screening, and toxicology.

  4. Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model

    Science.gov (United States)

    Sanzari, J. K.; Wan, X. S.; Wroe, A. J.; Rightnar, S.; Cengel, K. A.; Diffenderfer, E. S.; Krigsfeld, G. S.; Gridley, D. S.; Kennedy, A. R.

    2013-01-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel. PMID:23672458

  5. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2016-03-01

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition in a healthy

  6. Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Yue-Long Liang; Yi-Chen Yu; Kun Liu; Wei-Jia Wang; Jiang-Bo Ying; Yi-Fan Wang; Xiu-Jun Cai

    2012-01-01

    AIM:To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues.METHODS:Eight Ba-Ma mini-pigs were used in this study.Experimental models with common bile duct (CBD) defect (0.5-1.0 cm segment of CBD resected) were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co-(1,2-propanediol)].In addition,a vascularized greater omentum was placed around the stent and both ends of CBD.Cholangiography via gall bladder was performed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture.Complete blood count was examined pre-and post-operatively to estimate the inflammatory reaction.Liver enzymes and serum bilirubin were examined pre-and post-operatively to evaluate the liver function.Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis.The other three pigs were raised for one year for long-term observation.RESULTS:All the animals underwent surgery successfully.There was no intraoperative mortality and no bile leakage during the observation period.The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation,the difference was not statistically significant (P =0.652).The plasma level of alanine aminotransferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P =0.810).Nevertheless,the plasma level of γ-glutamyl transferase was increased after operation in both groups (P =0.004),especially 2 wk after operation.The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P =0.227),so did the serum direct bilirubin (P =0.759).By cholangiography via gall bladder,we found that the stent maintained its integrity of shape and was still in situ at month 1,and it disappeared

  7. An Ultrasound Image-Based Dynamic Fusion Modeling Method for Predicting the Quantitative Impact of In Vivo Liver Motion on Intraoperative HIFU Therapies: Investigations in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    W Apoutou N'Djin

    Full Text Available Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU, since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20 Hz, magnitude > 13 mm. Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96 Hz, magnitude 75%. Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3 · min(-1. To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions.

  8. Plasma levels of liver-specific miR-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia.

    Science.gov (United States)

    Andersson, Patrik; Gidlöf, Olof; Braun, Oscar O; Götberg, Matthias; van der Pals, Jesper; Olde, Björn; Erlinge, David

    2012-02-01

    Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n = 6) or normothermia (38°C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.

  9. Chronic subordinate colony housing (CSC as a model of chronic psychosocial stress in male rats.

    Directory of Open Access Journals (Sweden)

    Kewir D Nyuyki

    Full Text Available Chronic subordinate colony housing (CSC is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

  10. A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Jungersen, Gregers;

    2015-01-01

    predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system...... in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4(+)/CD8(+) double positive T cells. The genital immune system......Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good...

  11. Sex differences in the chronic mild stress model of depression.

    Science.gov (United States)

    Franceschelli, Anthony; Herchick, Samantha; Thelen, Connor; Papadopoulou-Daifoti, Zeta; Pitychoutis, Pothitos M

    2014-09-01

    A large volume of clinical and experimental evidence documents sex differences in brain anatomy, chemistry, and function, as well as in stress and drug responses. The chronic mild stress model (CMS) is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents despite the markedly higher prevalence of major depression among women. Herein, we review CMS studies conducted in rats and mice of both sexes and further discuss intriguing sex-dependent behavioral and neurobiological findings. The PubMed literature search engine was used to find and collect all relevant articles analyzed in this review. Specifically, a multitermed search was performed with 'chronic mild stress', 'chronic unpredictable stress' and 'chronic variable stress' as base terms and 'sex', 'gender', 'females' and 'depression' as secondary terms in various combinations. Male and female rodents appear to be differentially affected by CMS application, depending on the behavioral, physiological, and neurobiological indices that are being measured. Importantly, the CMS paradigm, despite its limitations, has been successfully used to assess a constellation of interdisciplinary research questions in the sex differences field and has served as a 'silver bullet' in assessing the role of sex in the neurobiology of major depression.

  12. A ferret model of COPD-related chronic bronchitis

    Science.gov (United States)

    Raju, S. Vamsee; Kim, Hyunki; Byzek, Stephen A.; Tang, Li Ping; Trombley, John E.; Jackson, Patricia; Rasmussen, Lawrence; Wells, J. Michael; Libby, Emily Falk; Winter, Lindy; Samuel, Sharon L.; Zinn, Kurt R.; Blalock, J. Edwin; Schoeb, Trenton R.; Dransfield, Mark T.; Rowe, Steven M.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway physiology and submucosal gland distribution. Here, we exposed ferrets to chronic cigarette smoke and found them to approximate complex clinical features of human COPD. Unlike mice, which develop solely emphysema, smoke-exposed ferrets exhibited markedly higher numbers of early-morning spontaneous coughs and sporadic infectious exacerbations as well as a higher level of airway obstruction accompanied by goblet cell metaplasia/hyperplasia and increased mucus expression in small airways, indicative of chronic bronchitis and bronchiolitis. Overall, we demonstrate the first COPD animal model exhibiting clinical and pathologic features of chronic bronchitis to our knowledge, providing a key advance that will greatly facilitate the preclinical development of novel treatments for this disease. PMID:27699245

  13. A Canine Model of Chronic Graft-versus-Host Disease.

    Science.gov (United States)

    Graves, Scott S; Rezvani, Andrew; Sale, George; Stone, Diane; Parker, Maura; Rosinski, Steven; Spector, Michele; Swearingen, Bruce; Kean, Leslie; Storb, Rainer

    2017-03-01

    In long-term survivors of allogeneic hematopoietic cell transplantation (HCT), chronic graft-versus-host disease (GVHD) is the major cause of morbidity and mortality and a major determinant of quality of life. Chronic GVHD responds poorly to current immunosuppressive drugs, and while T cell depletion may be preventive, this gain is offset by increased relapse rates. A significant impediment to progress in treating chronic GVHD has been the limitations of existing animal models. The goal of this study was to develop a reproducible comprehensive model of chronic GVHD in the dog. Ten recipient dogs received 920 cGy total body irradiation, infusion of marrow, and an infusion of buffy coat cells from a dog leukocyte antigen (DLA)-mismatched unrelated donor. Postgrafting immunosuppression consisted of methotrexate (days 1, 3, 6, 11) and cyclosporine. The duration of cyclosporine administration was limited to 80 days instead of the clinically used 180 days. This was done to contain costs, as chronic GVHD was expected to develop at earlier time points. All recipients were given ursodiol for liver protection. One dog had graft failure and 9 dogs showed stable engraftment. Eight of the 9 developed de novo chronic GVHD. Dogs progressed with clinical signs of chronic GVHD over a period of 43 to 164 (median, 88) days after discontinuation of cyclosporine. Target organs showed the spectrum of chronic GVHD manifestations that are typically seen clinically. These included lichenoid changes of the skin, fasciitis, ocular involvement (xerophthalmia), conjunctivitis, bronchiolitis obliterans, salivary gland involvement, gingivitis, esophageal involvement, and hepatic involvement. Peripheral blood lymphocyte surface antigen expression of CD28 and inducible costimulator was elevated in dogs with GHVD compared with those in normal dogs, but not significantly so. Serum levels of IL-8 and monocyte chemotactic protein-1 in GVHD-affected dogs at time of euthanasia were elevated, whereas

  14. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    Science.gov (United States)

    2014-01-01

    Background Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. Methods We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P < 0.001). Functional annotation identified pathways enlightening the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and

  15. Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Catherine C.; Baccam, Mekhine [Feminine Care Global Product Stewardship, 6110 Center Hill Road, The Procter and Gamble Company, Cincinnati, OH 45224 (United States); Mantz, Mary J. [Dows Institute for Dental Research, The University of Iowa, Iowa City, IA 52242 (United States); Osborn, Thomas W.; Hill, Donna R. [Feminine Care Product Development, 6110 Center Hill Road, The Procter and Gamble Company, Cincinnati, OH 45224 (United States); Squier, Christopher A. [Dows Institute for Dental Research, The University of Iowa, Iowa City, IA 52242 (United States)

    2014-01-15

    Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen—TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ({sup 3}H{sub 2}O) through porcine vaginal mucosa was determined at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52 °C) did not significantly increase flux of {sup 3}H{sub 2}O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of {sup 3}H{sub 2}O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment. - Highlights: • Model assessed local effects of tampon use on vaginal mucosa. • Risks were evaluated using two tracers to assess permeability in an ex vivo model. • Mechanical damage to the epithelial surface increased tracer penetration.

  16. Porcine liver: experimental model for the intra-hepatic glissonian approach Figado suíno: modelo experimental para o acesso glissoniano intra-hepático

    Directory of Open Access Journals (Sweden)

    Antonio Cavalcanti de Albuquerque Martins

    2008-04-01

    Full Text Available PURPOSE: The aim of the study is to evaluate the porcine liver as a teaching and training model for the glissonian approach. METHODS: Ten livers were removed from domestic adult white pigs weighting 35 to 45kg. Based on anatomical landmarks, the glissonian pedicles of each liver segments were dissected and biopsies were taken for histological examination, to analyze the presence of the glissonian sheath. RESULTS: During microscopic examination, a sheath of conjunctive tissue was observed wrapping each segmental pedicle in porcine liver. This could be clearly seen when histological preparation for connective tissue was obtained (Masson technique. CONCLUSION: The morphological arrangement of glissonian pedicles in porcine liver makes this model a useful tool for training the intra-hepatic glissonian approach.OBJETIVO: Avaliar a utilização do fígado suíno como um modelo experimental para o ensino e treinamento da técnica glissoniana intra-hepática nas ressecções do fígado. MÉTODOS: Foram utilizados 10 fígados inteiros de porcos adultos brancos, pesando entre 35-45 kg. Os pedículos glissonianos de vários segmentos foram dissecados e ressecados para a realização de estudos histológicos e verificação da presença da bainha conjuntiva ao longo das tríades portais. RESULTADOS: Na microscopia, uma bainha de tecido conjuntivo foi encontrada envolvendo os pedículos glissonianos no fígado suíno. A utilização de preparações específicas para o tecido conjuntivo (Masson ressaltou a presença dessa bainha em cada pedículo. CONCLUSÃO: As características morfológicas dos pedículos glissonianos suínos, fazem desse modelo experimental um método de treinamento da técnica glissoniana intra-hepática.

  17. Latent viral immune inflammatory response model for chronic multisymptom illness.

    Science.gov (United States)

    Maloney, Sean R; Jensen, Susan; Gil-Rivas, Virginia; Goolkasian, Paula

    2013-03-01

    A latent viral immune inflammatory response (LVIIR) model is presented which integrates factors that contribute to chronic multisymptom illness (CMI) in both the veteran and civilian populations. The LVIIR model for CMI results from an integration of clinical experience with a review of the literature in four distinct areas: (1) studies of idiopathic multisymptom illness in the veteran population including two decades of research on Gulf War I veterans with CMI, (2) new evidence supporting the existence of chronic inflammatory responses to latent viral antigens and the effect these responses may have on the nervous system, (3) recent discoveries concerning the role of vitamin D in maintaining normal innate and adaptive immunity including suppression of latent viruses and regulation of the immune inflammatory response, and (4) the detrimental effects of extreme chronic repetitive stress (ECRS) on the immune and nervous systems. The LVIIR model describes the pathophysiology of a pathway to CMI and presents a new direction for the clinical assessment of CMI that includes the use of neurological signs from a physical exam, objective laboratory data, and a new proposed latent viral antigen-antibody imaging technique for the peripheral and central nervous system. The LVIIR model predicts that CMI can be treated by a focus on reversal of immune system impairment, suppression of latent viruses and their antigens, and healing of nervous system tissue damaged by chronic inflammation associated with latent viral antigens and by ECRS. In addition, the LVIIR model suggests that maintaining optimal serum 25 OH vitamin D levels will maximize immune system suppression of latent viruses and their antigens and will minimize immune system inflammation. This model also emphasizes the importance of decreasing ECRS to improve immune system function and to minimize nervous system injury from excess serum glucocorticoid levels. The proposed model supports growing evidence that increasing

  18. Effects of a topical aqueous oxygen emulsion on collagen deposition and angiogenesis in a porcine deep partial-thickness wound model.

    Science.gov (United States)

    Li, Jie; Ollague Sierra, Jose; Zhu, Linjian; Tang, Ling; Rahill, Kirah; El-Sabawi, Bassim; Liu-Mares, Wen; Mertz, Patricia M; Davis, Stephen C

    2013-10-01

    A porcine deep partial-thickness wound model was used to evaluate the effects of a newly developed topical aqueous oxygen emulsion (TOE) on wound repair. The wounds were treated with TOE, which contains super-saturated oxygen or vehicle control. Semiquantitative immunofluorescent staining was performed to examine protein production for type I and type III collagen and vascular endothelial growth factor (VEGF). Immunofluorescent staining revealed higher protein levels of type I and type III collagen and VEGF in the TOE treatment group. Histological analysis also revealed improved angiogenesis and granulation tissue formation with topical TOE treatment and was consistent with the protein expression. In addition, the histology examination demonstrated faster epithelialization in wounds treated with TOE. The study suggests that sustained high levels of oxygen released by TOE may promote the process of wound repair through increasing collagen deposition and angiogenesis as well as stimulating epithelialization.

  19. Beyond pain: modeling decision-making deficits in chronic pain

    Science.gov (United States)

    Hess, Leonardo Emanuel; Haimovici, Ariel; Muñoz, Miguel Angel; Montoya, Pedro

    2014-01-01

    Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients’ behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals’ choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis. PMID:25136301

  20. Beyond pain: modeling decision-making deficits in chronic pain

    Directory of Open Access Journals (Sweden)

    Leonardo Emanuel Hess

    2014-08-01

    Full Text Available Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients’ behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls. In the present study, we developed a simple heuristic model to simulate individuals’ choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and healthy controls at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in healthy controls was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis.

  1. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik;

    2010-01-01

    was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV...... membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. CONCLUSIONS: Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from......PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...

  2. Clinical and histological findings after intravitreal injection of bevacizumsb (Avastin®) in a porcine model of choroidal neovascularisation

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik;

    2010-01-01

    was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV...... membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. CONCLUSIONS: Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from......PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...

  3. Chronic gastritis rat model and role of inducing factors

    Institute of Scientific and Technical Information of China (English)

    Zun Xiang; Jian-Min Si; Huai-De Huang

    2004-01-01

    AIM: To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa.METHODS: Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L8(27)orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined.RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P<0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy, In addition,indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied.CONCLUSION: Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only.The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated.

  4. In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pKa(FLUX) method for aqueous boundary layer correction and detailed data analysis.

    Science.gov (United States)

    Yusof, Siti R; Avdeef, Alex; Abbott, N Joan

    2014-12-18

    In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software

  5. Corneal-protective effects of an artificial tear containing sodium hyaluronate and castor oil on a porcine short-term dry eye model.

    Science.gov (United States)

    Hasegawa, Takashi; Amako, Hideki; Yamamoto, Takeshi; Tazawa, Mariko; Sakamoto, Yuji

    2014-09-01

    The corneal-protective effects of an artificial tear containing sodium hyaluronate (SH) and castor oil (CO) were evaluated on a porcine short-term dry eye model. Fresh porcine eyes with an intact cornea were treated with an artificial tear of saline, SH solution (0.1%, 0.5% or 1%), CO solution (0.5%, 1% or 5%) or a mixture solution containing 0.5% SH and 1% CO and then desiccated for 60, 90 or 180 min. To assess corneal damage, the eyes were stained with methylene blue (MB) or lissamine green (LG). The staining score of MB, absorbance of MB extracted from the cornea and staining density of LG increased significantly with increasing desiccation time in untreated and all artificial tear-treated eyes, although there were no significant differences in staining scores and absorbance of MB between eyes treated continuously with saline and 1% SH-treated ones at 60 and 90 min of desiccation or the mixture-treated eyes at 60 min of desiccation. No significant differences in the staining density of LG were also found between continuous saline-treated eyes and ones desiccated for 60 min and treated with 1% SH and the mixture. Mild cytoplasmic vacuolations were histopathologically observed in the basal and wing cells in eyes desiccated for 60 min and treated with 1% SH and the mixture. The mixture solution containing 0.5% SH and 1% CO has protective effects against corneal desiccation similar to those of 1% SH and would be helpful as an artificial tear.

  6. Magnetic resonance elastography of the lung parenchyma in an in situ porcine model with a noninvasive mechanical driver: correlation of shear stiffness with trans-respiratory system pressures.

    Science.gov (United States)

    Mariappan, Yogesh K; Kolipaka, Arunark; Manduca, Armando; Hubmayr, Rolf D; Ehman, Richard L; Araoz, Philip; McGee, Kiaran P

    2012-01-01

    Quantification of the mechanical properties of lung parenchyma is an active field of research due to the association of this metric with normal function, disease initiation and progression. A phase contrast MRI-based elasticity imaging technique known as magnetic resonance elastography is being investigated as a method for measuring the shear stiffness of lung parenchyma. Previous experiments performed with small animals using invasive drivers in direct contact with the lungs have indicated that the quantification of lung shear modulus with (1) H based magnetic resonance elastography is feasible. This technique has been extended to an in situ porcine model with a noninvasive mechanical driver placed on the chest wall. This approach was tested to measure the change in parenchymal stiffness as a function of airway opening pressure (P(ao) ) in 10 adult pigs. In all animals, shear stiffness was successfully quantified at four different P(ao) values. Mean (±STD error of mean) pulmonary parenchyma density corrected stiffness values were calculated to be 1.48 (±0.09), 1.68 (±0.10), 2.05 (±0.13), and 2.23 (±0.17) kPa for P(ao) values of 5, 10, 15, and 20 cm H2O, respectively. Shear stiffness increased with increasing P(ao) , in agreement with the literature. It is concluded that in an in situ porcine lung shear stiffness can be quantitated with (1) H magnetic resonance elastography using a noninvasive mechanical driver and that it is feasible to measure the change in shear stiffness due to change in P(ao) .

  7. Traumatization and chronic pain: a further model of interaction

    Directory of Open Access Journals (Sweden)

    Egloff N

    2013-11-01

    Full Text Available Niklaus Egloff,1 Anna Hirschi,2 Roland von Känel1 1Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University Hospital, Bern, Switzerland; 2Outpatient Clinic for Victims of Torture and War, Swiss Red Cross, Bern-Wabern, Switzerland Abstract: Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes. Keywords: posttraumatic stress disorder, chronic pain, hypermnesia, hypersensitivity, traumatization

  8. Porcine SLITRK1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Momeni, Jamal; Farajzadeh, Leila

    2014-01-01

    The membrane protein SLITRK1 functions as a developmentally regulated stimulator of neurite outgrowth and variants in this gene have been implicated in Tourette syndrome. In the current study we have cloned and characterized the porcine SLITRK1 gene. The genomic organization of SLITRK1 lacks...... introns, as does its human and mouse counterparts. RT-PCR cloning revealed two SLITRK1 transcripts: a full-length mRNA and a transcript variant that results in a truncated protein. The encoded SLITRK1 protein, consisting of 695 amino acids, displays a very high homology to human SLITRK1 (99%). The porcine...

  9. Modeling the effect of experimental variables on the in vitro permeation of six model compounds across porcine skin.

    Science.gov (United States)

    Karadzovska, Daniela; Brooks, James D; Riviere, Jim E

    2013-02-25

    A majority of quantitative structure-permeability relationships (QSPeRs) predict the permeability coefficient (k(p)) of compounds topically applied as infinite, saturated doses from water vehicles. Alternate delivery vehicles and other experimental variables are rarely incorporated in such models. This research presents the development and statistical validation of QSPeR models that incorporate the effects of penetrant, vehicle, and experimental conditions such as dose volume (finite/infinite), and saturation level (saturated/unsaturated). A composite parameter, a mixture factor (MF), was also included to account for the physicochemical properties of the compound/vehicle mixture components. The resultant models effectively described skin flux and absorption, identifying the summation of hydrogen bond acidity and basicity, excess molar refractivity, dose volume, saturation level, and vehicle as the most prominent factors influencing flux values. The main factors influencing absorption values were the summation of hydrogen bond basicity, dipolarity/polarizability, the McGowan characteristic volume, dose volume, saturation level, and vehicle. The same MF (inverse of the melting point) was considered suitable to describe both flux and absorption. For endpoints involving skin deposition, log propylene glycol solubility was a more suitable MF. Such models show potential for use in drug delivery and toxicology research, specifically in assessing percutaneous absorption data collected under different experimental conditions.

  10. A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity.

    Directory of Open Access Journals (Sweden)

    Sandeep Dhall

    Full Text Available Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.

  11. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  12. Sequence conservation between porcine and human LRRK2

    DEFF Research Database (Denmark)

    Larsen, Knud; Madsen, Lone Bruhn

    2009-01-01

     Leucine-rich repeat kinase 2 (LRRK2) is a member of the ROCO protein superfamily (Ras of complex proteins (Roc) with a C-terminal Roc domain). Mutations in the LRRK2 gene lead to autosomal dominant Parkinsonism. We have cloned the porcine LRRK2 cDNA in an attempt to characterize conserved...... and expression patterns are conserved across species. The porcine LRRK2 gene was mapped to chromosome 5q25. The results obtained suggest that the LRRK2 gene might be of particular interest in our attempt to generate a transgenic porcine model for Parkinson's disease...

  13. Pig model of chronic myocardial ischemia and its investigation by ultrasonic integrated backscatter and Doppler tissue imaging

    Institute of Scientific and Technical Information of China (English)

    XU Jing; ZHAO Bao-zhen; WANG Zhong; GU Jun-yan; LU Shi-ping

    2004-01-01

    Objective: To construct an animal model of chronic ischemic myocardium, and evaluate it by ultrasonic integrated backscatter (IBS) and Doppler tissue imaging (DTI). Methods: An Ameroid constrictor was placed around the porcine left circumflex coronary artery (LCX). The calibrated average image intensity ( % AII), cyclic variation of IBS(CVIB), transmural gradient index (TGI) of CVIB in lateral- posterior wall (LPW), and DTI spectrum of LPW in left ventricular papillary muscle level short axis view (LVPM-SAM) and apical four chamber view (AP-4CV) at normal state, 2, 4,6 and 8 weeks postoperatively were measured. Results: Normal %AII, CVIB and TGI were 2.29 ± 0.32, 9.69 ± 2.22dB and 0.22 ± 0.08, respectively. The % AII increased gradually postoperatively. The CVIB decreased also gradually, and the decrease was higher in subepicardium than in subendocardium. Most of TGI decrease occurred from 2 to 4 weeks postoperatively and became zero at 8 weeks (P < O. 01 ); Normal Vs (peak systolic velocity) of AP-4CV was higher than that of LVPM-SAM ( P < 0.01 ). VE (peak early diastolic velocity) of AP-4CV was lower than that of LVPM-SAM ( P < 0.05). Vs and VE were all decreased after operation ( P < 0.01 ). The decrease of Vs in AP-4CV was greater than that in LVPM-SAM.Conclusion: The pathological changes of the myocardium in human ischemic heart disease (IHD) are similar to that of Ameriod model. IBS and DTI can detect echo changes and ventricular wall motion in chronic ischemic myocardium, and provide more information for clinical investigation and treatment of IHD.

  14. Changes in chondrocyte gene expression following in vitro impaction of porcine articular cartilage in an impact injury model.

    Science.gov (United States)

    Ashwell, Melissa S; Gonda, Michael G; Gray, Kent; Maltecca, Christian; O'Nan, Audrey T; Cassady, Joseph P; Mente, Peter L

    2013-03-01

    Our objective was to monitor chondrocyte gene expression at 0, 3, 7, and 14 days following in vitro impaction to the articular surface of porcine patellae. Patellar facets were either axially impacted with a cylindrical impactor (25 mm/s loading rate) to a load level of 2,000 N or not impacted to serve as controls. After being placed in organ culture for 0, 3, 7, or 14 days, total RNA was isolated from full thickness cartilage slices and gene expression measured for 17 genes by quantitative real-time RT-PCR. Targeted genes included those encoding proteins involved with biological stress, inflammation, or anabolism and catabolism of cartilage extracellular matrix. Some gene expression changes were detected on the day of impaction, but most significant changes occurred at 14 days in culture. At 14 days in culture, 10 of the 17 genes were differentially expressed with col1a1 most significantly up-regulated in the impacted samples, suggesting impacted chondrocytes may have reverted to a fibroblast-like phenotype.

  15. Fixation of trapezial implants in a trapeziometacarpal total joint prosthesis tested in a model of porcine bone.

    Science.gov (United States)

    Hansen, Torben Bæk; Hengst, David; Mortensen, Jesper; Amstrup, Anders Læssøe

    2011-12-01

    High aseptic loosening rates have been reported in total joint prostheses of the carpometacarpal joint of the thumb, particularly in the trapezial component. The primary fixation of new implants may be tested in cadaver bones, but the anatomy of the pig is in many ways similar to that of the human, so we compared the central carpal bone from the forefoot of 6-month-old pigs, which has a saddle joint surface similar to the trapezium, to the trapezium in patients with carpometacarpal osteoarthritis. The mean (SD) bone mineral density of the 13 pig forefoot bones was 0.88 (0.12) g/cm(2) compared with 0.63 (0.16) g/cm(2) in the 31 human trapeziums. The measured size of the porcine bones was slightly larger than that of the human trapeziums. The similarity in form, size, and bone mineral density means that the central bone of the forefoot of 6-month-old pigs may be used for fixation tests in trapezial implants.

  16. The Impact of Prophylactic Fasciotomy Following Porcine (Sus scrofa) Hind Limb Ischemia/Reperfusion Injury

    Science.gov (United States)

    2012-03-23

    ANSI Std. Z39.18 The Impact of Prophylactic Fasciotomy Following Porcine (Sus scrofa ) Hind Limb Ischemia/reperfusion Injury CAPT Thomas J...porcine model of hind limb ischemia. Method: Swine (Sus Scrofa ; 76 +/-6kg) were randomly assigned to no fasciotomy or prophylactic fasciotomy after...of ischemic intervals on neuromuscular recovery in a porcine (Sus scrofa ) survival model of extremity vascular injury. J Vasc Surg. 2011 Jan;53(1):165

  17. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  18. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-11-12

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  19. Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

    Science.gov (United States)

    Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

    2016-09-29

    Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles.

  20. An ex vivo continuous passive motion model in a porcine knee for assessing primary stability of cell-free collagen gel plugs

    Directory of Open Access Journals (Sweden)

    El-Zayat Bilal

    2010-12-01

    Full Text Available Abstract Background Primary stability of cartilage repair constructs is of the utmost importance in the clinical setting but few continuous passive motion (CPM models are available. Our study aimed to establish a novel ex vivo CPM animal model and to evaluate the required motion cycles for testing the mechanical properties of a new cell-free collagen type I gel plug (CaReS®-1S. Methods A novel ex vivo CPM device was developed. Full-thickness cartilage defects (11 mm diameter by 6 mm deep were created on the medial femoral condyle of porcine knee specimens. CaReS®-1S was implanted in 16 animals and each knee underwent continuous passive motion. After 0, 2000, 4000, 6000, and 8000 motions, standardized digital pictures of the grafts were taken, focusing on the worn surfaces. The percentage of worn surface on the total CaReS®-1S surface was evaluated with image processing software. Results Significant differences in the worn surface were recorded between 0 and 2000 motion cycles (p ®-1S with an empty defect site was recorded. Conclusion The ex vivo CPM animal model is appropriate in investigating CaReS®-1S durability under continuous passive motion. 2000 motion cycles appear adequate to assess the primary stability of type I collagen gels used to repair focal chondral defects.

  1. Telomere reprogramming and maintenance in porcine iPS cells.

    Science.gov (United States)

    Ji, Guangzhen; Ruan, Weimin; Liu, Kai; Wang, Fang; Sakellariou, Despoina; Chen, Jijun; Yang, Yang; Okuka, Maja; Han, Jianyong; Liu, Zhonghua; Lai, Liangxue; Gagos, Sarantis; Xiao, Lei; Deng, Hongkui; Li, Ning; Liu, Lin

    2013-01-01

    Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.

  2. Splicing variants of porcine synphilin-1

    Directory of Open Access Journals (Sweden)

    Knud Larsen

    2015-09-01

    Full Text Available Parkinson's disease (PD, idiopathic and familial, is characterized by degradation of dopaminergic neurons and the presence of Lewy bodies (LB in the substantia nigra. LBs contain aggregated proteins of which α-synuclein is the major component. The protein synphilin-1 interacts and colocalizes with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa synphilin-1 cDNA (SNCAIP and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1 of 919 amino acids which shows a high similarity to human (90% and to mouse (84% synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation.

  3. A novel silk-based artificial ligament and tricalcium phosphate/polyether ether ketone anchor for anterior cruciate ligament reconstruction - safety and efficacy in a porcine model.

    Science.gov (United States)

    Li, Xiang; He, Jiankang; Bian, Weiguo; Li, Zheng; Zhang, Wenyou; Li, Dichen; Snedeker, Jess G

    2014-08-01

    Loss of ligament graft tension in early postoperative stages following anterior cruciate ligament (ACL) reconstruction can come from a variety of factors, with slow graft integration to bone being widely viewed as a chief culprit. Toward an off-the-shelf ACL graft that can rapidly integrate to host tissue, we have developed a silk-based ACL graft combined with a tricalcium phosphate (TCP)/polyether ether ketone anchor. In the present study we tested the safety and efficacy of this concept in a porcine model, with postoperative assessments at 3months (n=10) and 6months (n=4). Biomechanical tests were performed after euthanization, with ultimate tensile strengths at 3months of ∼370N and at 6months of ∼566N - comparable to autograft and allograft performance in this animal model. Comprehensive histological observations revealed that TCP substantially enhanced silk graft to bone attachment. Interdigitation of soft and hard tissues was observed, with regenerated fibrocartilage characterizing a transitional zone from silk graft to bone that was similar to native ligament bone attachments. We conclude that both initial stability and robust long-term biological attachment were consistently achieved using the tested construct, supporting a large potential for silk-TCP combinations in the repair of the torn ACL.

  4. Comparison of Sarns 3M heparin bonded to Duraflo II and control circuits in a porcine model: macro- and microanalysis of thrombi accumulation in circuit arterial filters.

    Science.gov (United States)

    Larson, D F; Arzouman, D; Kleinert, L; Patula, V; Williams, S

    2000-01-01

    Heparin-bonded perfusion circuits have been reported to reduce the thrombus formation during various levels of systemic heparinization. The goal of this study was to compare the efficacy of thrombo-resistance of the Sarns 3M heparin-bonded circuit to Baxter Duraflo II and untreated control in a porcine model. Fifteen Yorkshire pigs (60-65 kg) were anesthetized, heparinized with 3000 IU, intravenously (i.v.) and surgically cannulated with an internal jugular outflow and a femoral vein inflow. All circuits consisted of a 22-Fr venous cannula, centrifugal pump, arterial filter, an 18-Fr cannula for return and connected with equal lengths of 3/8" polyvinyl chloride tubing. The flows were maintained at 2.0 l/min for 4 h. Thrombus formation in filter samples were morphometrically analyzed through macro-densitometry, light microscopy, and scanning electron microscopy (SEM). Our findings revealed that the 3M circuit had significantly less gross thrombus (p < 0.001), 66% and 84% less microscopic thrombi and fivefold less SEM-measured aggregates (p = 0.03) compared to the Duraflo II and uncoated groups. This study demonstrated that the 3M heparin-bonded circuit had significantly reduced the formation of micro- and macro-thrombi in the minimally heparinized pig model compared to the Duraflo II and untreated control circuits.

  5. Comparison of Achilles tendon repair techniques in a sheep model using a cross-linked acellular porcine dermal patch and platelet-rich plasma fibrin matrix for augmentation.

    Science.gov (United States)

    Sarrafian, Tiffany L; Wang, Hali; Hackett, Eileen S; Yao, Jian Q; Shih, Mei-Shu; Ramsay, Heather L; Turner, A Simon

    2010-01-01

    The primary goal of this study was to evaluate a cross-linked acellular porcine dermal patch (APD), as well as platelet-rich plasma fibrin matrix (PRPFM), for repair of acute Achilles tendon rupture in a sheep model. The 2 surgically transected tendon ends were reapproximated in groups 1 and 2, whereas a gap was left between the tendon ends in group 3. APD was used to reinforce the repair in group 2, and autologous PRPFM was used to fill the gap, which was also reinforced with APD, in group 3. All sheep were humanely euthanized at 24 weeks after the repair, and biomechanical and histological testing were performed. Tensile strength testing showed a statistically significant difference in elongation between the operated limb and the unoperated contralateral limb in groups 1 and 3, but not in group 2. All operated tendons appeared healed with no apparent fibrosis under light and polarized microscopy. In group 1, all surgical separation sites were identifiable, and healing occurred via increasing tendon thickness. In group 2, healing occurred with new tendon fibers across the separation, without increasing tendon thickness in 2 out of 6 animals. Group 3 showed complete bridging of the gap, with no change in tendon thickness in 2 out of 6 animals. In groups 2 and 3, peripheral integration of the APD to tendon fibers was observed. These findings support the use of APD, alone or with PRPFM, to augment Achilles tendon repair in a sheep model.

  6. Porcine head response to blast

    Directory of Open Access Journals (Sweden)

    Jay eShridharani

    2012-05-01

    Full Text Available Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposed porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110-740 kPa peak incident overpressure with scaled durations from 1.3-6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. The bulk head acceleration and the pressure at the surface of the head and in the cranial cavity were measured. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within thirty seconds and the remaining two recovered within 8 minutes following bagging and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80-685 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385-3845 G’s and were well correlated with peak incident overpressure (R2=0.90. One standard deviation corridors for the surface pressure, intracranial pressure, and head acceleration are presented to provide experimental data for

  7. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk;

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  8. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lerberg; Afzelius, Pia; Bender, Dirk;

    2015-01-01

    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11......)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using...... a sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis...

  9. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole Lehberg; Afzelius, Pia; Bender, Dirk;

    2014-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  10. Advances on chronic heart failure in minipig models%小型猪慢性心力衰竭模型研究进展

    Institute of Scientific and Technical Information of China (English)

    应陈艇; 樊紫瑜; 牛小龙

    2016-01-01

    慢性心力衰竭是一种复杂的心血管综合征,建立合适的慢性心力衰竭动物模型是研究慢性心力衰竭发病机制及相关药物治疗的关键。小型猪因其在病理生理、解剖结构等方面更接近人类,故建立小型猪慢性心力衰竭模型已成为研究热点。目前较成熟的小型猪慢性心力衰竭模型制备方法主要有心肌梗死型、前负荷过载型、后负荷过载型、药源型和心动过速型等。%Chronic heart failure(CHF) is a complex cardiovascular syndrome.The establishment of an appropri⁃ate animal model of CHF is crucial for the study of pathogenesis and pharmacotherapy in CHF.Porcine models of chronic heart failure have became imperative because minipig is closer to human in physiopathology and anatomy. In recent years,the commonly used methods of minipig models of CHF are myocardial infarction,volume over⁃load,pressure overload,drug⁃induced and ventricular rapid pacing.

  11. Xenotransplantation and porcine cytomegalovirus.

    Science.gov (United States)

    Denner, Joachim

    2015-01-01

    Porcine microorganisms may be transmitted to the human recipient when xenotransplantation with pig cells, tissues, and organs will be performed. Most of such microorganisms can be eliminated from the donor pig by specified or designated pathogen-free production of the animals. As human cytomegalovirus causes severe transplant rejection in allotransplantation, considerable concern is warranted on the potential pathogenicity of porcine cytomegalovirus (PCMV) in the setting of xenotransplantation. On the other hand, despite having a similar name, PCMV is different from HCMV. The impact of PCMV infection on pigs is known; however, the influence of PCMV on the human transplant recipient is unclear. However, first transplantations of pig organs infected with PCMV into non-human primates were associated with a significant reduction of the survival time of the transplants. Sensitive detection methods and strategies for elimination of PCMV from donor herds are required.

  12. Isolation and culture of porcine neural progenitor cells from embryos and pluripotent stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel Aabech; Hall, Vanessa Jane; Hyttel, Poul

    2013-01-01

    therapy. The pig has become recognized as an important large animal model and establishment of in vitro-derived porcine NPCs would allow for preclinical safety testing by transplantation in a porcine biomedical model. In this chapter, a detailed method for isolation and in vitro culture of porcine NPCs...... from porcine embryos or induced pluripotent stem cells is presented. The neural induction is performed in coculture and the isolation of rosette structures is carried out manually to ensure a homogenous population of NPCs. Using this method, multipotent NPCs can be obtained in approximately 1 month...

  13. Neurological Disorders in a Murine Model of Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Jean-Marc Chillon

    2014-01-01

    Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

  14. Assessment of the diagnostic value of dual-energy CT and MRI in the detection of iatrogenically induced injuries of anterior cruciate ligament in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Fickert, S.; Niks, M.; Lehmann, L. [University Medical Center Mannheim, Center of Orthopaedics and Traumatology, Mannheim (Germany); Dinter, D.J.; Hammer, M.; Weckbach, S.; Schoenberg, S.O.; Jochum, S. [University Medical Center Mannheim, Department of Clinical Radiology and Nuclear Medicine, Mannheim (Germany)

    2013-03-15

    Magnetic resonance imaging (MRI) is the standard of reference for the non-invasive evaluation of ligament injuries of the knee. The development of dual-energy CT (DE-CT) made it possible to differentiate between tissues of different density by two simultaneous CT measurements with different tube voltages. This approach enables DE-CT to discriminate ligament structures without intra-articular contrast media injection. The aims of this study were on the one hand to determine the delineation of the anterior cruciate ligament (ACL) and on the other hand to assess the diagnostic value of DE-CT and MRI in the detection of iatrogenically induced injury of the ACL in a porcine knee joint model. Twenty porcine hind legs, which were placed in a preformed cast in order to achieve a standardized position, were scanned using DE-CT. Thereafter, a 1.5-T MRI using a standard protocol was performed. The imaging procedures were repeated with the same parameters after inducing defined lesions (total or partial incision) on the ACL arthroscopically. After post-processing, two radiologists and two orthopedic surgeons first analyzed the delineation of the ACL and then, using a consensus approach, the iatrogenically induced lesions. The result of the arthrotomy was defined as the standard of reference. The ACL could be visualized both on DE-CT and MRI in 100% of the cases. As for the MRI, the sensitivity and specificity of detecting the cruciate ligament lesion respectively compared with the defined arthrotomy was 66.7% and 78.6% for intact cruciate ligaments, 100% and 75% in the case of a complete lesion, 33.3% and 78.6% for lesions of the anteromedial bundle, and 0% and 100% for lesions of the posterolateral bundle. In comparison, DE-CT demonstrated a sensitivity and specificity of 66.7% and 71.4% in the case of intact cruciate ligaments, 75% and 68.8% in the case of completely discontinued ACLs, 0% and 92.9% in the case of lesions of the anteromedial bundle, and 25% and 87.5% in the

  15. Home-based chronic care. An expanded integrative model for home health professionals.

    Science.gov (United States)

    Suter, Paula; Hennessey, Beth; Harrison, Gregory; Fagan, Martha; Norman, Barbara; Suter, W Newton

    2008-04-01

    The Chronic Care Model (CCM) developed by is an influential and accepted guide for the care of patients with chronic disease. Wagner acknowledges a current healthcare focus on acute care needs that often circumvents chronic care coordination. He identifies the need for a "division of labor" to assist the primary care physician with this neglected function. This article posits that the role of chronic care coordination assistance and disease management fits within the purview of home healthcare and should be central to home health chronic care delivery. An expanded Home-Based Chronic Care Model (HBCCM) is described that builds on Wagner's model and integrates salient theories from fields beyond medicine. The expanded model maximizes the potential for disease self-management success and is intended to provide a foundation for home health's integral role in chronic disease management.

  16. On the global dynamics of a chronic myelogenous leukemia model

    Science.gov (United States)

    Krishchenko, Alexander P.; Starkov, Konstantin E.

    2016-04-01

    In this paper we analyze some features of global dynamics of a three-dimensional chronic myelogenous leukemia (CML) model with the help of the stability analysis and the localization method of compact invariant sets. The behavior of CML model is defined by concentrations of three cellpopulations circulating in the blood: naive T cells, effector T cells specific to CML and CML cancer cells. We prove that the dynamics of the CML system around the tumor-free equilibrium point is unstable. Further, we compute ultimate upper bounds for all three cell populations and provide the existence conditions of the positively invariant polytope. One ultimate lower bound is obtained as well. Moreover, we describe the iterative localization procedure for refining localization bounds; this procedure is based on cyclic using of localizing functions. Applying this procedure we obtain conditions under which the internal tumor equilibrium point is globally asymptotically stable. Our theoretical analyses are supplied by results of the numerical simulation.

  17. Effect of angiopoietin-related protein 2 on coronary angiogenesis and myocardial function in a porcine model of acute myocardial ischemia

    Institute of Scientific and Technical Information of China (English)

    Shu Meng; Changqian Wang; Fei Wang; Renjian Zhou; Fangbao Ding; Fuxin Chen

    2008-01-01

    Our previous studies have suggested that angiopoietin-related protein 2 (Arp2) may improve rat cardiac function after acute myocardial infarction (AMI) by accelerating angiogenesis.We want to study the efficacy of the adenoviral vector-mediated gene transfer of Arp2 (Ad.Arp2) in inducing angiogenesis and in improving the myocardial perfusion and function in a porcine acute myocardial ischemic model.Methods The minipigs underwent ligation of the proximal circumflex coronary artery (LCx) and were randomly assigned to treatment with Ad.Arp2,adenoviral vectors with no transgene (Ad.Null) or PBS.Four weeks later,the animals were evaluated using echocardiography,cardiac perfusion imaging and pathologic observation.Results Four weeks after treatment,the Arp2 protein was revealed in the myocardium of Ad.Arp2 animals,but was not found in the Ad.Null or PBS animals.Also,a significant revival of myocardial perfusion was found in the ischemic area in Ad.Arp2-treated animals,whose global and regional myocardial function was greatly improved.The quantitation of new capillaries was much greater in the Ad.Arp2 group than in the Ad.Null or PBS groups.Conclusion Treatment with Ad.ARP2 offers the obvious advantage of greatly improving the blood supply and the heart function.(J Geriatr Cardiol 2008;5:230-234)

  18. A head-to-head hands-on comparison of ERCP mechanical simulator (EMS) and Ex-vivo Porcine Stomach Model (PSM).

    Science.gov (United States)

    Leung, Joseph W; Wang, Dong; Hu, Bing; Lim, Brian; Leung, Felix W

    2011-07-01

    BACKGROUND: ERCP mechanical simulator (EMS) and ex-vivo porcine stomach model (PSM) have been described. No direct comparison was reported on endoscopists' perception regarding their efficacy for ERCP training OBJECTIVE: Comparative assessment of EMS and PSM. DESIGN: Questionnaire survey before and after practice. SETTING: Hands-on practice workshops. SUBJECTS: 22 endoscopists with prior experience in 111±225 (mean±SD) ERCP. INTERVENTIONS: Participants performed scope insertion, selective bile duct cannulation with guide wire and insertion of a single biliary stent. Simulated fluoroscopy with external pin-hole camera (EMS), or with additional transillumination (PSM) was used to monitor exchange of accessories. MAIN OUTCOME MEASURE: Participants rated their understanding and confidence before and after hands-on practice, and credibility of each simulator for ERCP training. Comparative efficacy of EMS and PSM for ERCP education was scored (1=not, 10=very) based on pre and post practice surveys: realism (tissue pliability, papilla anatomy, visual/cannulation realism, wire manipulation, simulated fluoroscopy, overall experience); usefulness (assessment of results, supplementing clinical experience, easy for trainees to learn new skills) and application (overall ease of use, prepare trainees to use real instrument and ease of incorporation into training). RESULTS: Before hands-on practice, both EMS and PSM received high scores. After practice, there was a significantly greater increase in confidence score for EMS than PSM (pPSM credible options for improving understanding and supplementing clinical ERCP training. EMS is more useful for basic learning.

  19. SPECT imaging of myocardial infarction using {sup 99m}Tc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model

    Energy Technology Data Exchange (ETDEWEB)

    Fang Wei [Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037 (China); Wang Feng [Nuclear Medicine Department, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006 (China); Ji Shundong [Jiangsu Institute of Hematology, 1st Hospital of Suzhou University, Suzhou 215006 (China); Zhu Xiaoguang [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Meier, Heidi T. [Clinical Veterinarian and Radiology Research, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, WI 53295 (United States); Hellman, Robert S. [Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Brindle, Kevin M. [MRC Laboratory of Molecular Biology, Cambridge CB2 2QH (United Kingdom); Davletov, Bazbek [Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA (United Kingdom); Zhao Ming [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States)], E-mail: mzhao@mcw.edu

    2007-11-15

    Introduction: The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of {sup 99m}Tc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology. Methods: Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. {sup 99m}Tc-C2A-GST (n=7) or {sup 99m}Tc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with {sup 99m}Tc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death. Results: Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with {sup 99m}Tc-BSA or in noninfarct animals with {sup 99m}Tc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2{+-}5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction. Conclusions: We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.

  20. Validation of 99mTechnetium-labeled mebrofenin hepatic extraction method to quantify meal-induced splanchnic blood flow responses using a porcine model

    DEFF Research Database (Denmark)

    Zacho, Helle Damgaard; Kristensen, Niels Bastian; Henriksen, Jens Henrik Sahl;

    2012-01-01

    The aim of this study was to evaluate the measurement of the total splanchnic blood flow (SBF) using a clinical diagnostic method based on Fick's principle and hepatic extraction of 99mTc-mebrofenin (99mTc-MBF) compared with a paraaminohippuric acid (pAH) dilution method in a porcine model. Another...... or metabolism. The clinical method for measuring the SBF based on hepatic 99mTc-MBF extraction is robust compared with the indicator dilution method, despite the decrease seen in hepatic extraction of 99mTc-MBF. Because there was no difference in the content of 99mTc-MBF between the arterial and portal vein...... aim was to investigate whether enterohepatic cycling of 99mTc-MBF affected the SBF measurement. Five indwelling catheters were placed in each pig (n = 15) in the portal, mesenteric, and hepatic veins, as well as in the aorta and the vena cava. The SBF was measured using both methods. The portal blood...

  1. Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

    Institute of Scientific and Technical Information of China (English)

    Yi-Ping Li; Hye Na Kang; Lorne A Babiuk; Qiang Liu

    2006-01-01

    AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models.METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation,ELISPOT for the number of interferon-γ secreting cells,and cytotoxic T lymphocyte assays.RESULTS: Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-like ones in piglets.CONCLUSION: A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations.

  2. Vascular replacement using a layered elastin-collagen vascular graft in a porcine model: one week patency versus one month occlusion.

    Science.gov (United States)

    Koens, M J W; Krasznai, A G; Hanssen, A E J; Hendriks, T; Praster, R; Daamen, W F; van der Vliet, J A; van Kuppevelt, T H

    2015-01-01

    A persistent clinical demand exists for a suitable arterial prosthesis. In this study, a vascular conduit mimicking the native 3-layered artery, and constructed from the extracellular matrix proteins type I collagen and elastin, was evaluated for its performance as a blood vessel equivalent. A tubular 3-layered graft (elastin-collagen-collagen) was prepared using highly purified type I collagen fibrils and elastin fibers, resembling the 3-layered native blood vessel architecture. The vascular graft was crosslinked and heparinised (37 ± 4 μg heparin/mg graft), and evaluated as a vascular graft using a porcine bilateral iliac artery model. An intra-animal comparison with clinically-used heparinised ePTFE (Propaten®) was made. Analyses included biochemical characterization, duplex scanning, (immuno)histochemistry and scanning electron microscopy. The tubular graft was easy to handle with adequate suturability. Implantation resulted in pulsating grafts without leakage. One week after implantation, both ePTFE and the natural acellular graft had 100% patencies on duplex scanning. Grafts were partially endothelialised (Von Willebrand-positive endothelium with a laminin-positive basal membrane layer). After one month, layered thrombi were found in the natural (4/4) and ePTFE graft (1/4), resulting in occlusion which in case of the natural graft is likely due to the porosity of the inner elastin layer. In vivo application of a molecularly-defined tubular graft, based on nature's matrix proteins, for vascular surgery is feasible.

  3. Rat models of asthma and chronic obstructive lung disease.

    Science.gov (United States)

    Martin, James G; Tamaoka, Meiyo

    2006-01-01

    The rat has been extensively used to model asthma and somewhat less extensively to model chronic obstructive pulmonary disease (COPD). The features of asthma that have been successfully modeled include allergen-induced airway constriction, eosinophilic inflammation and allergen-induced airway hyperresponsiveness. T-cell involvement has been directly demonstrated using adoptive transfer techniques. Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13). Repeated allergen exposure causes airway remodeling. Dry gas hyperpnea challenge also evokes increases in lung resistance, allowing exercise-induced asthma to be modeled. COPD is modeled using elastase-induced parenchymal injury to mimic emphysema. Cigarette smoke-induced airspace enlargement occurs but requires months of cigarette exposure. Inflammation and fibrosis of peripheral airways is an important aspect of COPD that is less well modeled. Novel approaches to the treatment of COPD have been reported including treatments aimed at parenchymal regeneration.

  4. IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

    2016-03-01

    Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

  5. Salt-Induced Changes in Cardiac Phosphoproteome in a Rat Model of Chronic Renal Failure

    OpenAIRE

    Zhengxiu Su; Hongguo Zhu; Menghuan Zhang; Liangliang Wang; Hanchang He; Shaoling Jiang; Fan Fan Hou; Aiqing Li

    2014-01-01

    Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl...

  6. The porcine ear skin as a model system for the human integument: influence of storage conditions on basic features of epidermis structure and function--a histological and histochemical study.

    Science.gov (United States)

    Meyer, W; Zschemisch, N H; Godynicki, S

    2003-01-01

    Based on careful tissue processing, detailed structural analysis, and histochemical as well as cytophotometrical evaluation of the epidermis, the study presents data with respect to changes of tissue integrity during two storing modes (room temperature and 4 degrees C) and various storage times of the porcine auricle. Structural degeneration was first noted in the barrier region of the epidermis from where such changes spread, independent of storage conditions, from small horizontal necrotic islands and continuously with increasing storage time. The histochemical results corroborated these observations, emphasizing, however, that the lower epidermal layers seemed intact for a longer time period than the upper layers. Cytophotometrical evaluation of histochemical stainings showed, with regard to the enzyme succinate dehydrogenase, that oxidative metabolism was negatively affected in the early stages of storage, whereas epidermal lipids (neutral fats, glycolipids) remained relatively stable, even during storage at room temperature. In conclusion, it was obvious that the barrier region is the most sensitive element of the porcine ear epidermis. Taking into consideration that this part of the epidermis is most important for permeation studies, it seems reasonable to avoid any storage of porcine auricles at room temperature, and to use only auricles that have been stored at 4 degrees C for not more than 4 to 6 hours, immediately after delivery from the slaughter-house. In this way better tissue preservation can be achieved, whereby the use of shinkage-free water-soluble plastic embedding would generally improve the histological control of structural integrity, and the application of an easy to handle enzyme histochemical procedure (e.g. succinate dehydrogenase demonstration) to unfixed fresh-frozen sections would help to control basic aspects of tissue functions. The results are discussed in relation to the use of porcine integument as a model in human dermatological

  7. An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein

    OpenAIRE

    Ahmadi, Abbas; Nikkhoo, Bahram; Mokarizadeh, Aram; Rahmani, Mohammad-Reza; Fakhari, Shohreh; Mohammadi, Mehdi; Jalili, Ali

    2016-01-01

    Introduction Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treate...

  8. The healthy learner model for student chronic condition management--part I.

    Science.gov (United States)

    Erickson, Cecelia DuPlessis; Splett, Patricia L; Mullett, Sara Stoltzfus; Heiman, Mary Bielski

    2006-12-01

    A significant number of children have chronic health conditions that interfere with normal activities, including school attendance and active participation in the learning process. Management of students' chronic conditions is complex and requires an integrated system. Models to improve chronic disease management have been developed for the medical system and public health. Programs that address specific chronic disease management or coordinate school health services have been implemented in schools. Lacking is a comprehensive, integrated model that links schools, students, parents, health care, and other community providers. The Healthy Learner Model for chronic condition management identifies seven elements for creating, implementing, and sustaining an efficient and effective, comprehensive community-based system for improving the management of chronic conditions for school children. It has provided the framework for successful chronic condition management in an urban school district and is proposed for replication in other districts and communities.

  9. Adapting chronic care models for diabetes care delivery inlow-and-middle-income countries: A review

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    A contextual review of models for chronic care was doneto develop a context-adapted chronic care model-basedservice delivery model for chronic conditions includingdiabetes. The Philippines was used as the setting ofa low-to-middle-income country. A context-basednarrative review of existing models for chronic carewas conducted. A situational analysis was done at thegrassroots level, involving the leaders and members ofthe community, the patients, the local health system andthe healthcare providers. A second analysis making useof certain organizational theories was done to explore onimproving feasibility and acceptability of organizing carefor chronic conditions. The analyses indicated that carefor chronic conditions may be introduced, consideringthe needs of people with diabetes in particular andthe community in general as recipients of care, andthe issues and factors that may affect the healthcareworkers and the health system as providers of thiscare. The context-adapted chronic care model-basedservice delivery model was constructed accordingly.Key features are incorporation of chronic care in thehealth system's services; assimilation of chronic caredelivery with the other responsibilities of the healthcareworkers but with redistribution of certain tasks; andensuring that the recipients of care experience thewhole spectrum of basic chronic care that includes educationand promotion in the general population, riskidentification, screening, counseling including self-caredevelopment, and clinical management of the chroniccondition and any co-morbidities, regardless of level ofcontrol of the condition. This way, low-to-middle incomecountries can introduce and improve care for chronicconditions without entailing much additional demand ontheir limited resources.

  10. Generation of a Stable Transgenic Swine Model Expressing a Porcine Histone 2B-eGFP Fusion Protein for Cell Tracking and Chromosome Dynamics Studies

    Science.gov (United States)

    Simpson, Sean; Collins, Bruce; Sommer, Jeff; Petters, Robert M.; Caballero, Ignacio; Platt, Jeff L.

    2017-01-01

    Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B). This fusion protein is targeted to the nucleosomes resulting a nuclear/chromatin eGFP signal. The first model (I) was generated via random insertion of pH2B-eGFP driven by the CAG promoter (chicken beta actin promoter and rabbit Globin poly A; pCAG-pH2B-eGFP) and protected by human interferon-β matrix attachment regions (MARs). Despite the consistent, high, and ubiquitous expression of the fusion protein pH2B-eGFP in all tissues analyzed, two independently generated Model I transgenic lines developed neurodegenerative symptoms including Wallerian degeneration between 3–5 months of age, requiring euthanasia. A second transgenic model (II) was developed via CRISPR-Cas9 mediated homology-directed repair (HDR) of IRES-pH2B-eGFP into the endogenous β-actin (ACTB) locus. Model II transgenic animals showed ubiquitous expression of pH2B-eGFP on all tissues analyzed. Unlike the pCAG-pH2B-eGFP/MAR line, all Model II animals were healthy and multiple pregnancies have been established with progeny showing the expected Mendelian ratio for the transmission of the pH2B-eGFP. Expression of pH2B-eGFP was used to examine the timing of the maternal to zygotic transition after IVF, and to examine chromosome segregation of SCNT embryos. To our knowledge this is the first viable transgenic pig model with chromatin-associated eGFP allowing both cell tracking and the study of chromatin dynamics in a large animal model. PMID:28081156

  11. Novel porcine repetitive elements

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2006-12-01

    Full Text Available Abstract Background Repetitive elements comprise ~45% of mammalian genomes and are increasingly known to impact genomic function by contributing to the genomic architecture, by direct regulation of gene expression and by affecting genomic size, diversity and evolution. The ubiquity and increasingly understood importance of repetitive elements contribute to the need to identify and annotate them. We set out to identify previously uncharacterized repetitive DNA in the porcine genome. Once found, we characterized the prevalence of these repeats in other mammals. Results We discovered 27 repetitive elements in 220 BACs covering 1% of the porcine genome (Comparative Vertebrate Sequencing Initiative; CVSI. These repeats varied in length from 55 to 1059 nucleotides. To estimate copy numbers, we went to an independent source of data, the BAC-end sequences (Wellcome Trust Sanger Institute, covering approximately 15% of the porcine genome. Copy numbers in BAC-ends were less than one hundred for 6 repeat elements, between 100 and 1000 for 16 and between 1,000 and 10,000 for 5. Several of the repeat elements were found in the bovine genome and we have identified two with orthologous sites, indicating that these elements were present in their common ancestor. None of the repeat elements were found in primate, rodent or dog genomes. We were unable to identify any of the replication machinery common to active transposable elements in these newly identified repeats. Conclusion The presence of both orthologous and non-orthologous sites indicates that some sites existed prior to speciation and some were generated later. The identification of low to moderate copy number repetitive DNA that is specific to artiodactyls will be critical in the assembly of livestock genomes and studies of comparative genomics.

  12. Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.

    Directory of Open Access Journals (Sweden)

    Wenru Su

    Full Text Available Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs.

  13. Targeted Porcine Genome Engineering with TALENs

    DEFF Research Database (Denmark)

    Luo, Yonglun; Lin, Lin; Golas, Mariola Monika;

    2015-01-01

    Genetically modified pigs are becoming an invaluable animal model for agricultural, pharmaceutical, and biomedical applications. Unlike traditional transgenesis, which is accomplished by randomly inserting an exogenous transgene cassette into the natural chromosomal context, targeted genome editing...... confers precisely editing (e.g., mutations or indels) or insertion of a functional transgenic cassette to user-designed loci. Techniques for targeted genome engineering are growing dramatically and include, e.g., zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs......, including construction of sequence-specific TALENs, delivery of TALENs into primary porcine fibroblasts, and detection of TALEN-mediated cleavage, is described. This chapter is useful for scientists who are inexperienced with TALEN engineering of porcine cells as well as of other large animals....

  14. Managing painful chronic wounds: the Wound Pain Management Model

    DEFF Research Database (Denmark)

    Price, Patricia; Fogh, Karsten; Glynn, Chris;

    2007-01-01

    document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr......Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...

  15. Evaluation of adenosine preconditioning with {sup 99m}Tc-His{sub 10}-annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Ye Fei [Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Fang Wei [Cardiovascular Institute and Fuwai Hospital, No. 167 Bei-Li-Shi-Lu, Beijing 100037 (China); Wang Feng, E-mail: fengwang1972cn@gmail.co [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Hua Zichun [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Wang Zizheng [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing 210006 (China); Yang Xiang [State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2011-05-15

    Purpose: The goal of this study was to evaluate the feasibility of {sup 99m}Tc-His{sub 10}-annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods: {sup 99m}Tc-His{sub 10}-annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of {sup 99m}Tc-His{sub 10}-annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20-30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model (n=14). Adenosine was infused intravenously in six pigs before coronary occlusion. {sup 99m}Tc-His{sub 10}-annexin V (n=12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with {sup 99m}Tc-MIBI was also performed 1 day after His{sub 10}-annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results: {sup 99m}Tc-His{sub 10}-annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of {sup 99m}Tc-His{sub 10}-annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His{sub 10}-annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of {sup 99m}Tc-His{sub 10}-annexin was found in the risk area which showed no defects in the {sup 99m}Tc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly

  16. Tissue damage by laser radiation: an in vitro comparison between Tm:YAG and Ho:YAG laser on a porcine kidney model.

    Science.gov (United States)

    Huusmann, Stephan; Wolters, Mathias; Kramer, Mario W; Bach, Thorsten; Teichmann, Heinrich-Otto; Eing, Andreas; Bardosi, Sebastian; Herrmann, Thomas R W

    2016-01-01

    The understanding of tissue damage by laser radiation is very important for the safety in the application of surgical lasers. The objective of this study is to evaluate cutting, vaporization and coagulation properties of the 2 µm Tm:YAG laser (LISA Laser Products OHG, GER) in comparison to the 2.1 µm Ho:YAG laser (Coherent Medical Group, USA) at different laser power settings in an in vitro model of freshly harvested porcine kidneys. Laser radiation of both laser generators was delivered by using a laser fiber with an optical core diameter of 550 µm (RigiFib, LISA Laser GER). Freshly harvested porcine kidneys were used as tissue model. Experiments were either performed in ambient air or in aqueous saline. The Tm:YAG laser was adjusted to 5 W for low and 120 W for the high power setting. The Ho:YAG laser was adjusted to 0.5 J and 10 Hz (5 W average power) for low power setting and to 2.0 J and 40 Hz (80 W average power) for high power setting, accordingly. The specimens of the cutting experiments were fixed in 4 % formalin, embedded in paraffin and stained with Toluidin blue. The laser damage zone was measured under microscope as the main evaluation criteria. Laser damage zone consists of an outer coagulation zone plus a further necrotic zone. In the ambient air experiments the laser damage zone for the low power setting was 745 ± 119 µm for the Tm:YAG and 614 ± 187 µm for the Ho:YAG laser. On the high power setting, the damage zone was 760 ± 167 µm for Tm:YAG and 715 ± 142 µm for Ho:YAG. The incision depth in ambient air on the low power setting was 346 ± 199 µm for Tm:YAG, 118 ± 119 µm for Ho:YAG. On the high power setting incision depth was 5083 ± 144 µm (Tm:YAG) and 1126 ± 383 µm (Ho:YAG) respectively. In the saline solution experiments, the laser damage zone was 550 ± 137 µm (Tm:YAG) versus 447 ± 65 µm (Ho:YAG), on the low power setting and 653 ± 137 µm (Tm:YAG) versus 677 ± 134 µm (Ho

  17. A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Jungersen, Gregers;

    2015-01-01

    is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5-5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary...

  18. Genome-wide Linkage Disequilibrium Linkage Analysis (LDLA) of Body Fat Traits in an F2 Porcine Model for Human Obesity

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Cirera Salicio, Susanna;

    , body composition was determined at about two months of age (64 ± 11 days) via dual-energy xray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined LDLA approach was used to perform genomewide linkage and association analysis for body fat traits...

  19. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

    Science.gov (United States)

    Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-01-01

    Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

  20. Natural orifice transluminal endoscopic wedge hepatic resection with a water-jet hybrid knife in a non-survival porcine model

    Institute of Scientific and Technical Information of China (English)

    Hong Shi; Sheng-Jun Jiang; Bin Li; Deng-Ke Fu; Pei Xin; Yong-Guang Wang

    2011-01-01

    AIM:To explore the feasibility of a water-jet hybrid knife to facilitate wedge hepatic resection using a natural orifice transluminal endoscopic surgery (NOTES) approach in a non-survival porcine model.METHODS:The Erbe Jet2 water-jet system allows a needleless,tissue-selective hydro-dissection with a preselected pressure.Using this system,wedge hepatic resection was performed through three natural routes (trans-anal,trans-vaginal and trans-umbilical) in three female pigs weighing 35 kg under general anesthesia.Entry into the peritoneal cavity was via a 15-mm incision using a hook knife.The targeted liver segment was marked by an APC probe,followed by wedge hepatic resection performed using a water-jet hybrid knife with the aid of a 4-mm transparent distance soft cap mounted onto the tip of the endoscope for holding up the desired plane.The exposed vascular and ductal structures were clipped with Endoclips.Hemostasis was applied to the bleeding cut edges of the liver parenchyma by electrocautery.After the procedure,the incision site was left open,and the animal was euthanized followed by necropsy.RESULTS:Using the Erbe Jet2 water-jet system,transanal and trans-vaginal wedge hepatic resection was successfully performed in two pigs without laparoscopic assistance.Trans-umbilical attempt failed due to an unstable operating platform.The incision for peritoneal entry took 1 min,and about 2 h was spent on excision of the liver tissue.The intra-operative blood loss ranged from 100 to 250 mL.Microscopically,the hydro-dissections were relatively precise and gentle,preserving most vessels.CONCLUSION:The Erbe Jet2 water-jet system can safely accomplish non-anatomic wedge hepatic resection in NOTES,which deserves further studies to shorten the dissection time.

  1. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model.

    Directory of Open Access Journals (Sweden)

    K Horst

    Full Text Available Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.Male pigs (35 ± 5kg were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min. After resuscitation, hypothermia (33°C was induced for a period of 12 h (HT-T group with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma cytokine levels (IL-6, -8, -10 and alarmins (HMGB1, HSP70 were measured via ELISA.Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.

  2. Beneficial antimicrobial effect of the addition of an aminoglycoside to a β-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.

    Directory of Open Access Journals (Sweden)

    Paul Skorup

    Full Text Available This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9, a combination of cefuroxime+tobramycin (n = 9, or saline (control, n = 9. Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR. Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001. Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01; no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05. High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05. The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  3. Determining the effect of an oak bark formulation on methicillin-resistant staphylococcus aureus and wound healing in porcine wound models.

    Science.gov (United States)

    Davis, Stephen C; Mertz, Patricia M

    2008-10-01

    Control of wound infections, especially those associated with methicillin-resistant Staphylococcus aureus, is necessary for the wound healing process. Selection of topical agents should be based not only on their ability to eliminate pathogenic bacteria, but also on whether they may be detrimental to tissue repair. Two randomized, controlled in vivo studies using different porcine models were conducted to evaluate the effect of a topical oak bark ointment (treatment) on 1) methicillin-resistant Staphylococcus aureus in partial-thickness wounds, and 2) healing of second-degree burn wounds. Silver sulfadiazine, oak bark ointment vehicle control (polyethylene glycol), and no treatment (untreated wounds) were used as controls in both studies. In the first study, 108 partial-thickness wounds in three animals were inoculated with a methicillin-resistant S. aureus suspension (average 6.96+/-0.4 log CFU/mL) and covered for 24 hours with a polyurethane film. After polyurethane film removal, treatments were applied twice daily and nine wounds per day (three per animal) from each treatment group were cultured after 24, 48, and 72 hours. Methicillin-resistant S. aureus colonization was lowest in the active treatment group at all three assessment times and after 72 hours ranged from (5.01+/-1.1 CFU/mL) in the treatment to (6.20+/-0.8 CFU/mL) in the vehicle control treated wounds. In the second study, treatments were applied twice daily to second-degree burn wounds (n = 720) on eight animals. Daily epithelialization assessment (n = five wounds) was performed on day 7 through 10 after wounding. At every assessment time, the proportion of wounds healed was higher in the treatment than in the control treatment groups - days 8, 9, and 10 (active versus vehicle and untreated), P healing in vivo. Research to ascertain the importance of these findings for clinical practice is needed.

  4. Computed tomography scout views vs. conventional radiography in body-packers – Delineation of body-packs and radiation dose in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Ziegeler, Edvard, E-mail: edvard.ziegeler@campus.lmu.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Nussbaumstraße 20, 80336 Munich (Germany); Grimm, Jochen M., E-mail: jochen.grimm@med.lmu.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Nussbaumstraße 20, 80336 Munich (Germany); Wirth, Stefan, E-mail: tefan.wirth@med.lmu.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Nussbaumstraße 20, 80336 Munich (Germany); Uhl, Michael, E-mail: michael.uhl@polizei.bayern.de [Bavarian State Criminal Police Office, Maillingerstrasse 15, 80636 Munich (Germany); Reiser, Maximilian F., E-mail: Maximilian.Reiser@med.lmu.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Nussbaumstraße 20, 80336 Munich (Germany); Scherr, Michael K., E-mail: Michael.Scherr@med.lmu.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Nussbaumstraße 20, 80336 Munich (Germany)

    2012-12-15

    Objective: To compare abdominal computed tomography (CT) scout views with conventional radiography regarding radiation dose and delineation of drug packages in a porcine body-packer model. Materials and methods: Nine samples of illicit drugs packed in ovoid plastic containers were consecutively placed in the rectum of a 121.5 kg pig cadaver. Antero-posterior and lateral scout views were obtained at 120 kVp and 80 mA, 150 mA and 200 mA, respectively, using a 64-row MDCT. Scout views were compared with conventional abdominal antero-posterior radiographs (77 kV and 106 ± 13 mAs). Visibility of three body pack characteristics (wrapping, content, shape) was rated independently by two radiologists and summarized to a delineation score ranging from 0 to 9 with a score ≥6 representing sufficient delineation. Mean delineation scores were calculated for each conventional radiography and single plane scout view separately and for a combined rating of antero-posterior and lateral scout views. Results: Even the lowest single plane scout view delineation score (5.3 ± 2.0 for 80 mA lateral; 0.4 mSv; sensitivity = 44%) was significantly higher than for conventional radiographs (3.1 ± 2.5, p < 0.001; 2.4 ± 0.3 mSv; sensitivity = 11%). Combined reading of antero-posterior and lateral scout views 80 mA yielded sufficient delineation (6.2 ± 1.4; 0.8 mSv; sensitivity = 56%). Conclusions: All CT scout views showed significantly better delineation ratings and sensitivity than conventional radiographs. Scout views in two planes at 80 mA provided a sufficient level of delineation and a sensitivity five times higher than conventional radiography at less than one third of the radiation dose. In case of diagnostic insecurity, CT can be performed without additional logistical effort.

  5. Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

    Science.gov (United States)

    Carlsson, Anders H; Rose, Lloyd F; Fletcher, John L; Wu, Jesse C; Leung, Kai P; Chan, Rodney K

    2017-02-01

    Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300μm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (pskin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision.

  6. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model

    Science.gov (United States)

    Horst, K.; Eschbach, D.; Pfeifer, R.; Relja, B.; Sassen, M.; Steinfeldt, T.; Wulf, H.; Vogt, N.; Frink, M.; Ruchholtz, S.; Pape, H. C.; Hildebrand, F.

    2016-01-01

    Background Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. Materials & Methods Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA. Results Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h. Conclusion A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application. PMID:27144532

  7. Porcine prion protein amyloid.

    Science.gov (United States)

    Hammarström, Per; Nyström, Sofie

    2015-01-01

    Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

  8. Automated EEG monitoring in defining a chronic epilepsy model.

    Science.gov (United States)

    Mascott, C R; Gotman, J; Beaudet, A

    1994-01-01

    There has been a recent surge of interest in chronic animal models of epilepsy. Proper assessment of these models requires documentation of spontaneous seizures by EEG, observation, or both in each individual animal to confirm the presumed epileptic condition. We used the same automatic seizure detection system as that currently used for patients in our institution and many others. Electrodes were implanted in 43 rats before intraamygdalar administration of kainic acid (KA). Animals were monitored intermittently for 3 months. Nine of the rats were protected by anticonvulsants [pentobarbital (PB) and diazepam (DZP)] at the time of KA injection. Between 1 and 3 months after KA injection, spontaneous seizures were detected in 20 of the 34 unprotected animals (59%). Surprisingly, spontaneous seizures were also detected during the same period in 2 of the 9 protected animals that were intended to serve as nonepileptic controls. Although the absence of confirmed spontaneous seizures in the remaining animals cannot exclude their occurrence, it indicates that, if present, they are at least rare. On the other hand, definitive proof of epilepsy is invaluable in the attempt to interpret pathologic data from experimental brains.

  9. 5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

    Institute of Scientific and Technical Information of China (English)

    Yongquan Pan; Peng Zhang; Junqing Yang; Qiang Su

    2010-01-01

    A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum.In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-lipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage andspatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

  10. Advances in porcine genomics and proteomics - a toolbox for developing the pig as a model organism for molecular biomedical research

    DEFF Research Database (Denmark)

    Bendixen, Emøke; Danielsen, Marianne; Larsen, Knud

    2010-01-01

    Our current knowledge of human biology is often based on studying a wide range of animal species. In particular, for understanding human diseases, the development of adequate animal models is of immediate importance. Although genetic strains and transgenic animal model organisms like fruit fly...

  11. Screening and Characterization of Spontaneous Porcine Congenital Heart Defects for Gene Identification and Models of Human Disease

    Science.gov (United States)

    Background: Rodent models of human congenital birth defects have been instrumental for gene discovery and investigation of mechanisms of disease. However, these models are limited by their small size making practiced intervention or detailed anatomic evaluation difficult. Swine have similar anato...

  12. A novel porcine model of implant associated osteomyelitis: a comprehensive analysis of local, regional and systemic response

    DEFF Research Database (Denmark)

    Jensen, Louise Kruse; Koch, Janne; Dich-Jorgensen, Kirstine;

    2017-01-01

    Pigs are favorable experimental animals for infectious diseases in humans. However, implant associated osteomyelitis (IAO) models in pigs have only been evaluated using high-inoculum infection (>108 CFU) models in 1975 and 1993. Therefore, the aim of this paper was to present a new low inoculum...

  13. Advances in porcine genomics and proteomics - a toolbox for developing the pig as a model organism for molecular biomedical research

    DEFF Research Database (Denmark)

    Bendixen, Emøke; Danielsen, Marianne; Larsen, Knud;

    2010-01-01

    Our current knowledge of human biology is often based on studying a wide range of animal species. In particular, for understanding human diseases, the development of adequate animal models is of immediate importance. Although genetic strains and transgenic animal model organisms like fruit fly (D...

  14. Does Glucagon Improve Survival in a Porcine (Sus Scrofa) of Adult Asphyxial Cardiac Arrest in Addition to Standard Epinephrine Therapy?

    Science.gov (United States)

    2012-01-17

    UDIIILI: oa. I..UN I ItA!.. I NUMDI:It Does Glucagon improve survival in a porcine (Sus Scrofa ) of adult asphyxial cardiac arrest in addition to...EXPIRATION DATE: 25 Mar 13 PROTOCOL TITLE: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial Cardiac Arrest in Addition...Additions: Deletions: 2 Protocol No: A-2007-03 Protocol Title: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial

  15. New porcine test-model reveals remarkable differences between algorithms for spectrophotometrical haemoglobin saturation measurements with VLS

    DEFF Research Database (Denmark)

    Gade, John; Greisen, Gorm

    2016-01-01

    The study created an 'ex vivo' model to test different algorithms for measurements of mucosal haemoglobin saturation with visible light spectrophotometry (VLS). The model allowed comparison between algorithms, but it also allowed comparison with co-oximetry using a 'gold standard' method. This has......  -32.8 to  +29.9 percentage points and from  -5.0 to  +9.2 percentage points, respectively. CONCLUSION: the algorithms showed remarkable in-between differences when tested on raw-spectra from an 'ex vivo' model. All algorithms had bias, more marked at high oxygenation than low oxygenation. Three...

  16. Mathematical modeling of genesis and treatment of chronic myeloid leukemia.

    Science.gov (United States)

    Horn, Matthias; Loeffler, Markus; Roeder, Ingo

    2008-01-01

    Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder induced by translocation of chromosomes 9 and 22, resulting in an overproduction of myeloid blood cells. CML-specific characteristics include a latency time of several years, a period of coexistence of malignant and normal cells and an eventual dominance of the malignant clone. Different drug therapies are available, most notably imatinib, which inhibits the oncogenic BCR-ABL1 tyrosine kinase. Although the chromosomal aberration causing CML is well known, the resulting dynamic effects on the system behavior are not sufficiently understood yet. Here, we apply an already established mathematical model of hematopoietic stem cell organization. Based on parameter estimates for normal hematopoiesis, we systematically explore the changes in these parameters necessary to reproduce CML-specific characteristics regarding emergence and course of disease as well as a variety of qualitative and quantitative clinical data on CML treatment. Our results indicate that 1 or more of the following mechanisms are compatible with the induction of a dominant clone in the proposed model: a retarded differentiation process, a reduced turnover time or a defective cell-microenvironment interaction of the neoplastic cells. However, in order to explain the massive overproduction of malignant cells, an unregulated and abnormal activation of leukemia stem cells into cycle has to be assumed additionally. Based on our simulation results we conclude that CML dynamics can most appropriately be explained by a modulation of the cell-microenvironment interactions of leukemia stem cells, including both the process of stem cell silencing and activation into cycle.

  17. Pediatric Fear-Avoidance Model of Chronic Pain: Foundation, Application and Future Directions

    Directory of Open Access Journals (Sweden)

    Gordon JG Asmundson

    2012-01-01

    Full Text Available The fear-avoidance model of chronic musculoskeletal pain has become an increasingly popular conceptualization of the processes and mechanisms through which acute pain can become chronic. Despite rapidly growing interest and research regarding the influence of fear-avoidance constructs on pain-related disability in children and adolescents, there have been no amendments to the model to account for unique aspects of pediatric chronic pain. A comprehensive understanding of the role of fear-avoidance in pediatric chronic pain necessitates understanding of both child/adolescent and parent factors implicated in its development and maintenance. The primary purpose of the present article is to propose an empirically-based pediatric fear-avoidance model of chronic pain that accounts for both child/adolescent and parent factors as well as their potential interactive effects. To accomplish this goal, the present article will define important fear-avoidance constructs, provide a summary of the general fear-avoidance model and review the growing empirical literature regarding the role of fear-avoidance constructs in pediatric chronic pain. Assessment and treatment options for children with chronic pain will also be described in the context of the proposed pediatric fear-avoidance model of chronic pain. Finally, avenues for future investigation will be proposed.

  18. Distinct properties and metabolic mechanisms of postresuscitation myocardial injuries in ventricular fibrillation cardiac arrest versus asphyxiation cardiac arrest in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Wu Caijun; Li Chunsheng; Zhang Yi; Yang Jun

    2014-01-01

    Background The two most prevalent causes of sudden cardiac death are ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA).Profound postresuscitation myocardial dysfunction has been demonstrated in both VFCA and ACA animal models.Our study aimed to characterize the two porcine models of cardiac arrest and postresuscitation myocardial metabolism dysfunction.Methods Thirty-two pigs were randomized into two groups.The VFCA group (n=16) were subject to programmed electrical stimulation and the ACA group (n=16) underwent endotracheal tube clamping to induce cardiac arrest (CA).Once induced,CA remained untreated for a period of 8 minutes.Two minutes following initiation of cardiopulmonary resuscitation (CPR),defibrillation was attempted until return of spontaneous circulation (ROSC) was achieved or animals died.To assess myocardial metabolism,18F-FluoroDeoxyGlucose Positron Emission Tomography was performed at baseline and 4 hours after ROSC.Results ROSC was 100% successful in VFCA and 50% successful in ACA.VFCA had better mean arterial pressure and cardiac output after ROSC than ACA.Arterial blood gas analysis indicated more detrimental metabolic disturbances in ACA compared with VFCA after ROSC (ROSC 0.5 hours,pH:7.01±0.06 vs.7.21±0.03,P<0.01; HCO3-:(15.83±2.31 vs.20.11±1.83) mmol/L,P<0.01; lactate:(16.22±1.76 vs.5.84±1.44) mmol/L,P<0.01).Myocardial metabolism imaging using Positron Emission Tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA at 4 hours after ROSC (the maximum standardized uptake value of the whole left ventricular:1.00±0.17 vs.1.93±0.27,P<0.01).Lower contents of myocardial energy metabolism enzymes (Na+-K+-ATPase enzyme activity,Ca2+-ATPase enzyme activity,superoxide dismutase and phosphodiesterase) were found in ACA relative to VFCA.Conclusions Compared with VFCA,ACA causes more severe myocardium injury and metabolism hindrance,therefore they

  19. A low protein diet during pregnancy provokes a lasting shift of hepatic expression of genes related to cell cycle throughout ontogenesis in a porcine model

    Directory of Open Access Journals (Sweden)

    Oster Michael

    2012-03-01

    Full Text Available Abstract Background In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. Adverse environmental conditions during fetal development provoke an intrauterine adaptive response termed 'fetal programming', which may lead to both persistently biased responsiveness to extrinsic factors and permanent consequences for the organismal phenotype. This leads to the hypothesis that the offspring's transcriptome exhibits short-term and long-term changes, depending on the maternal diet. In order to contribute to a comprehensive inventory of genes and functional networks that are targets of nutritional programming initiated during fetal life, we applied whole-genome microarrays for expression profiling in a longitudinal experimental design covering prenatal, perinatal, juvenile, and adult ontogenetic stages in a porcine model. Pregnant sows were fed either a gestational low protein diet (LP, 6% CP or an adequate protein diet (AP, 12% CP. All offspring was nursed by foster sows receiving standard diets. After weaning, all offspring was fed standard diets ad libitum. Results Analyses of the hepatic gene expression of the offspring at prenatal (94 dies post conceptionem, dpc and postnatal stages (1, 28, 188 dies post natum, dpn included comparisons between dietary groups within stages as well as comparisons between ontogenetic stages within diets to separate diet-specific transcriptional changes and maturation processes. We observed differential expression of genes related to lipid metabolism (e.g. Fatty acid metabolism, Biosynthesis of steroids, Synthesis and degradation of ketone bodies, FA elongation in mitochondria, Bile acid synthesis and cell cycle regulation (e.g. Mitotic roles of PLK, G1/S checkpoint regulation, G2/M DNA damage checkpoint regulation. Notably, at stage 1 dpn no regulation of a distinct pathway was found in LP offspring. Conclusions The transcriptomic

  20. Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo;

    2015-01-01

    text] between susceptible and resistant strains in the absence of a drug was not different. EC 50 increased linearly with MIC on a log-log scale, and γ was different between susceptible and resistant strains. The in vitro model parameters described the inhibition effect of tetracycline on E. coli when...... of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E max model with three...... parameters: maximum net growth rate (α max ); concentration for a half-maximal response (E max ); and the Hill coefficient (γ). The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline...

  1. Myocardial ischemic preconditioning in a porcine model leads to rapid changes in cardiac extracellular vesicle messenger RNA content

    Directory of Open Access Journals (Sweden)

    Kristina Svennerholm

    2015-09-01

    Conclusions: These findings demonstrate in an in vivo model that myocardial ischemic preconditioning influences the composition of mRNA in EV, including gene transcripts for proteins associated with the protective effect of ischemic preconditioning. The finding that preconditioned parental cells release EV containing mRNA that is qualitatively different from those released by non-preconditioned cells shows the importance of the external milieu on parental cell EV production.

  2. The large shear strain dynamic behaviour of in-vitro porcine brain tissue and a silicone gel model material.

    Science.gov (United States)

    Brands, D W; Bovendeerd, P H; Peters, G W; Wismans, J S

    2000-11-01

    The large strain dynamic behaviour of brain tissue and silicone gel, a brain substitute material used in mechanical head models, was compared. The non-linear shear strain behaviour was characterised using stress relaxation experiments. Brain tissue showed significant shear softening for strains above 1% (approximately 30% softening for shear strains up to 20%) while the time relaxation behaviour was nearly strain independent. Silicone gel behaved as a linear viscoelastic solid for all strains tested (up to 50%) and frequencies up to 461 Hz. As a result, the large strain time dependent behaviour of both materials could be derived for frequencies up to 1000 Hz from small strain oscillatory experiments and application of Time Temperature Superpositioning. It was concluded that silicone gel material parameters are in the same range as those of brain tissue. Nevertheless the brain tissue response will not be captured exactly due to increased viscous damping at high frequencies and the absence of shear softening in the silicone gel. For trend studies and benchmarking of numerical models the gel can be a good model material.

  3. Evaluation of chronic immune system stimulation models in growing pigs.

    Science.gov (United States)

    Rakhshandeh, A; de Lange, C F M

    2012-02-01

    substantial reductions in feed intake and ADG, whereas MYCO did not induce effective ISS. In EXP II, ISS increased relative organ weights, eye temperature, white blood cell count and plasma acute-phase proteins (P < 0.05), confirming that repeated injection with increasing amounts of LPS induced chronic and relatively mild ISS. Repeated injection with increasing amounts of LPS is a suitable model for studying nutrient metabolism and evaluating the efficacy of nutritional intervention during chronic ISS in growing pigs.

  4. Characterization of a new rat model for chronic inflammatory demyelinating polyneuropathies.

    Science.gov (United States)

    Brun, Susana; Beaino, Wissam; Kremer, Laurent; Taleb, Omar; Mensah-Nyagan, Ayikoe Guy; Lam, Chanh D; Greer, Judith M; de Seze, Jérôme; Trifilieff, Elisabeth

    2015-01-15

    Our objective was to develop a chronic model of EAN which could be used as a tool to test treatment strategies for CIDP. Lewis rats injected with S-palmitoylated P0(180-199) peptide developed a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology. The late phase of the chronic disease was characterized by accumulation of IL-17(+) cells and macrophages in sciatic nerves and by high serum IL-17 levels. In conclusion, we have developed a reliable and reproducible animal model resembling CIDP that can now be used for translational drug studies.

  5. Pharmacodynamic modelling of in vitro activity of tetracycline against a representative, naturally occurring population of porcine Escherichia coli

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo;

    2015-01-01

    of Escherichia coli representative of those found in the Danish pig population, we compared the growth of 50 randomly selected strains. The observed net growth rates were used to describe the in vitro pharmacodynamic relationship between drug concentration and net growth rate based on E max model with three...... parameters: maximum net growth rate (α max ); concentration for a half-maximal response (E max ); and the Hill coefficient (γ). The net growth rate in the absence of antibiotic did not differ between susceptible and resistant isolates (P = 0.97). The net growth rate decreased with increasing tetracycline...

  6. Sustained inflation and incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation in a large porcine model of acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Wunder Christian

    2006-06-01

    Full Text Available Abstract Background To compare the effect of a sustained inflation followed by an incremental mean airway pressure trial during conventional and high-frequency oscillatory ventilation on oxygenation and hemodynamics in a large porcine model of early acute respiratory distress syndrome. Methods Severe lung injury (Ali was induced in 18 healthy pigs (55.3 ± 3.9 kg, mean ± SD by repeated saline lung lavage until PaO2 decreased to less than 60 mmHg. After a stabilisation period of 60 minutes, the animals were randomly assigned to two groups: Group 1 (Pressure controlled ventilation; PCV: FIO2 = 1.0, PEEP = 5 cmH2O, VT = 6 ml/kg, respiratory rate = 30/min, I:E = 1:1; group 2 (High-frequency oscillatory ventilation; HFOV: FIO2 = 1.0, Bias flow = 30 l/min, Amplitude = 60 cmH2O, Frequency = 6 Hz, I:E = 1:1. A sustained inflation (SI; 50 cmH2O for 60s followed by an incremental mean airway pressure (mPaw trial (steps of 3 cmH2O every 15 minutes were performed in both groups until PaO2 no longer increased. This was regarded as full lung inflation. The mPaw was decreased by 3 cmH2O and the animals reached the end of the study protocol. Gas exchange and hemodynamic data were collected at each step. Results The SI led to a significant improvement of the PaO2/FiO2-Index (HFOV: 200 ± 100 vs. PCV: 58 ± 15 and TAli: 57 ± 12; p 2-reduction (HFOV: 42 ± 5 vs. PCV: 62 ± 13 and TAli: 55 ± 9; p Ali: 6.1 ± 1 vs. T75: 3.4 ± 0.4; PCV: TAli: 6.7 ± 2.4 vs. T75: 4 ± 0.5; p Conclusion A sustained inflation followed by an incremental mean airway pressure trial in HFOV improved oxygenation at a lower mPaw than during conventional lung protective ventilation. HFOV but not PCV resulted in normocapnia, suggesting that during HFOV there are alternatives to tidal ventilation to achieve CO2-elimination in an "open lung" approach.

  7. Interphase chromosome positioning in in vitro porcine cells and ex vivo porcine tissues

    Directory of Open Access Journals (Sweden)

    Foster Helen A

    2012-11-01

    Full Text Available Abstract Background In interphase nuclei of a wide range of species chromosomes are organised into their own specific locations termed territories. These chromosome territories are non-randomly positioned in nuclei which is believed to be related to a spatial aspect of regulatory control over gene expression. In this study we have adopted the pig as a model in which to study interphase chromosome positioning and follows on from other studies from our group of using pig cells and tissues to study interphase genome re-positioning during differentiation. The pig is an important model organism both economically and as a closely related species to study human disease models. This is why great efforts have been made to accomplish the full genome sequence in the last decade. Results This study has positioned most of the porcine chromosomes in in vitro cultured adult and embryonic fibroblasts, early passage stromal derived mesenchymal stem cells and lymphocytes. The study is further expanded to position four chromosomes in ex vivo tissue derived from pig kidney, lung and brain. Conclusions It was concluded that porcine chromosomes are also non-randomly positioned within interphase nuclei with few major differences in chromosome position in interphase nuclei between different cell and tissue types. There were also no differences between preferred nuclear location of chromosomes in in vitro cultured cells as compared to cells in tissue sections. Using a number of analyses to ascertain by what criteria porcine chromosomes were positioned in interphase nuclei; we found a correlation with DNA content.

  8. The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model

    Science.gov (United States)

    Lindqvist, Andreas; Ekelund, Mikael; Garcia-Vaz, Eliana; Ståhlman, Marcus; Pierzynowski, Stefan; Gomez, Maria F.; Rehfeld, Jens F.; Groop, Leif; Hedenbro, Jan

    2017-01-01

    Background A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. Methods In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. Results A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs. Conclusion In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period. PMID:28257455

  9. Infrared laser sealing of porcine tissues: preliminary in vivo studies

    Science.gov (United States)

    Cilip, Christopher M.; Hutchens, Thomas C.; Kerr, Duane; Latimer, Cassandra; Rosenbury, Sarah B.; Giglio, Nicholas C.; Schweinsberger, Gino R.; Perkins, William C.; Wilson, Christopher R.; Ward, Arlen; Nau, William H.; Fried, Nathaniel M.

    2015-02-01

    We are exploring infrared (IR) lasers as an alternative energy modality to radiofrequency (RF) and ultrasonic (US) devices intended to provide rapid surgical hemostasis with minimal collateral zones of thermal damage and tissue necrosis. Previously, a 1470-nm IR laser sealed and cut ex vivo porcine renal arteries of 1-8 mm in 2 s, yielding burst pressures porcine model. A prototype, fiber optic based handheld probe with vessel/tissue clasping mechanism was tested on blood vessels Collagen denaturation averaged 1.6 mm in 8 samples excised for histologic examination. A handheld laser probe sealed porcine vessels in vivo. With further improvements in probe design and laser parameter optimization, IR lasers may provide an alternative to RF and US vessel sealing devices.

  10. A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

    Directory of Open Access Journals (Sweden)

    Michael Oster

    Full Text Available In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP or an adequate protein diet (AP, 12% CP throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc and postnatal stages (1, 28, 188 dpn. Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

  11. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

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    Arheden Håkan

    2010-09-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg, a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8 or saline (9 mg/ml, n = 8. Area at risk (AAR was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007. Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23. The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  12. Edaravone, a hydroxyl radical scavenger, ameliorates the severity of pulmonary hypertension in a porcine model of neonatal sepsis.

    Science.gov (United States)

    Yamaguchi, Sachiko; Hussein, Mohamed Hamed; Daoud, Ghada AbdEl-Hamid; Goto, Tatenobu; Kato, Shin; Kakita, Hiroki; Mizuno, Haruo; Ito, Tetsuya; Fukuda, Sumio; Kato, Ineko; Suzuki, Satoshi; Hashimoto, Takashi; Togari, Hajime

    2011-01-01

    Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.

  13. Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

    Directory of Open Access Journals (Sweden)

    Otto Andreas

    2010-01-01

    Full Text Available Abstract Background Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO in a large animal model. Methods A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg. The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8 or saline (0.9 mg/ml, n = 8, twenty minutes after balloon inflation. Area at risk (AAR was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI. Results No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS, but apyrase prolonged the post-ischemic reactive hyperemia. Conclusion Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.

  14. Expression of Matrix Metalloproteinase-9 and -12 in Porcine Lung Infections

    DEFF Research Database (Denmark)

    Bruun, C. S.; Leifsson, P. S.; Johansen, L. K.

    2012-01-01

    Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in the immune response and during acute and chronic diseases as well as in tissue remodelling. During the last decade, the pig has become used increasingly as a model for human diseases; however, studies on the express...... expressions were seen in the alveolar epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in accordance with studies of human lungs....... on the expression of porcine MMPs are limited. In the present study species-specific antibodies were produced to investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs from pigs infected with Actinobacillus pleuropneumoniae, Pasteurella multocida and Staphylococcus aureus. The immunolabelling...... of lung tissues (one infected and one control pig representing each infection) was evaluated for cellular distribution and intensity, which was scored semiquantitatively. When compared with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was higher in infected lungs. The highest...

  15. 7 CFR 1230.611 - Porcine animal.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  16. Deciphering the porcine intestinal microRNA transcriptome

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2010-04-01

    Full Text Available Abstract Background While more than 700 microRNAs (miRNAs are known in human, a comparably low number has been identified in swine. Because of the close phylogenetic distance to humans, pigs serve as a suitable model for studying e.g. intestinal development or disease. Recent studies indicate that miRNAs are key regulators of intestinal development and their aberrant expression leads to intestinal malignancy. Results Here, we present the identification of hundreds of apparently novel miRNAs in the porcine intestine. MiRNAs were first identified by means of deep sequencing followed by miRNA precursor prediction using the miRDeep algorithm as well as searching for conserved miRNAs. Second, the porcine miRNAome along the entire intestine (duodenum, proximal and distal jejunum, ileum, ascending and transverse colon was unraveled using customized miRNA microarrays based on the identified sequences as well as known porcine and human ones. In total, the expression of 332 intestinal miRNAs was discovered, of which 201 represented assumed novel porcine miRNAs. The identified hairpin forming precursors were in part organized in genomic clusters, and most of the precursors were located on chromosomes 3 and 1, respectively. Hierarchical clustering of the expression data revealed subsets of miRNAs that are specific to distinct parts of the intestine pointing to their impact on cellular signaling networks. Conclusions In this study, we have applied a straight forward approach to decipher the porcine intestinal miRNAome for the first time in mammals using a piglet model. The high number of identified novel miRNAs in the porcine intestine points out their crucial role in intestinal function as shown by pathway analysis. On the other hand, the reported miRNAs may share orthologs in other mammals such as human still to be discovered.

  17. STUDY ON INFLAMMATORY CELLS IN BALF OF SMOKE-INDUCED CHRONIC BRONCHITIS RAT MODEL

    Institute of Scientific and Technical Information of China (English)

    李庆云; 黄绍光; 吴华成; 程齐俭; 项轶; 万欢英

    2004-01-01

    Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the pathological change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lavage fluid (BALF) in various stages. Methods Chronic bronchitis sequential rat model was established by passively inhaling smoke mixture. Experiments were performed in 30 young male Sprague-Dawley rats, which comprised 5 groups in random, i.e.,4 chronic bronchitis model groups and I control group. After stained with hematoxylin and eosin, the specimens were studied by semi-quantitative method to evaluate the morphologic changes in various stages. Meanwhile, the inflammatory cells of the BALF and the activity of myeloperoxidase ( MPO ) of lung tissue were analysed. Results During the process of the chronic bronchitis, the pathologic score was increasing as time went on, and the typical morphologic changes of chronic bronchitis emerged in the group 7 weeks. The total number of inflammatory cells in BALF was increasing as time went on, correlated with the pathologic scores ( P < 0. 01 ).And the percentage of lymphocyte increased as well as positively correlated with pathologic scores ( P < 0. 05 ),whereas that of macrophage decreased and negatively correlated with pathologic scores (P <0. 05). The MPO lever of lung tissue was correlated with the pathologic scores ( P < 0. 01 ). But the percentage of the neutrophil in the BALF was just in a high level during the first week, then it maintained relatively lower. Conclusion Smoke-induced chronic bronchitis is a slowly progressive inflammation process. The model we established is convenient and simple for the longitudinal study on the inflammatory process of chronic bronchitis and the therapy in the early stage. The semi-quantitative evaluation for the pathological change is with much more value. During the inflammatory sequential process of early stage of chronic bronchitis, the cellular characteristics are

  18. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

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    Robert Nunan

    2014-11-01

    Full Text Available The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

  19. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity.

    Science.gov (United States)

    Nunan, Robert; Harding, Keith G; Martin, Paul

    2014-11-01

    The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound - defined as a barrier defect that has not healed in 3 months - has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

  20. A mouse model for pathogen-induced chronic inflammation at local and systemic sites.

    Science.gov (United States)

    Papadopoulos, George; Kramer, Carolyn D; Slocum, Connie S; Weinberg, Ellen O; Hua, Ning; Gudino, Cynthia V; Hamilton, James A; Genco, Caroline A

    2014-08-08

    Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation. Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies

  1. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders;

    2010-01-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core...

  2. A longitudinal study of cell-mediated immunity in pigs infected with porcine parvovirus

    DEFF Research Database (Denmark)

    Ladekjaer-Mikkelsen, A.S.; Nielsen, Jens

    2002-01-01

    Porcine parvovirus (PPV) is an ubiquitous pathogen causing reproductive failure in swine. Protection against reproductive failure caused by acute PPV infection has commonly been related to the presence of specific antibodies in the dam. However, the role of cell-mediated immunity during chronic PPV...

  3. Integrating the Chronic Care Model into a Novel Medical Student Course

    Science.gov (United States)

    Block, Robert C.; Tran, Bill; McIntosh, Scott

    2011-01-01

    Objective: To determine whether integration of the Chronic Care Model into undergraduate medical education is associated with anticipated use of the Model and whether student perceptions match actual integration of the Model into their community projects. Design: This was a cross-sectional study using qualitative and quantitative data. Setting: A…

  4. Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

    2016-04-01

    There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats.

  5. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    Science.gov (United States)

    Ramírez-Romero, Rafael; Nevárez-Garza, Alicia M.; Rodríguez-Tovar, Luis E.; Wong-González, Alfredo; Ledezma-Torres, Rogelio A.; Hernández-Vidal, Gustavo

    2012-01-01

    Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model. PMID:22629176

  6. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    Directory of Open Access Journals (Sweden)

    Rafael Ramírez-Romero

    2012-01-01

    Full Text Available Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP and chronic obstructive pulmonary disease (COPD in human beings, calves are proposed as an alternative animal model.

  7. L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

    Institute of Scientific and Technical Information of China (English)

    Zhihua Wang; Jinghua Li; Zhiming Wang; Lingyan Xue; Yi Zhang; Yingjie Chen; Jun Su; Zhongming Li

    2012-01-01

    Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

  8. Peculiarity of Porcine Amniotic Membrane and Its Derived Cells: A Contribution to the Study of Cell Therapy from a Large Animal Model.

    Science.gov (United States)

    Lange-Consiglio, Anna; Corradetti, Bruna; Bertani, Sabrina; Notarstefano, Valentina; Perrini, Claudia; Marini, Maria Giovanna; Arrighi, Silvana; Bosi, Giampaolo; Belloli, Angelo; Pravettoni, Davide; Locatelli, Valentina; Cremonesi, Fausto; Bizzaro, Davide

    2015-12-01

    The aim of this work was to provide, for the first time, a protocol for isolation and characterization of stem cells from porcine amniotic membrane in view of their potential uses in regenerative medicine. From three samples of allanto-amnion recovered at delivery, the amniotic membrane was stripped from overlying allantois and digested with trypsin and collagenase to isolate epithelial (amniotic epithelial cells [AECs]) and mesenchymal cells, respectively. Proliferation, differentiation, and characterization studies by molecular biology and flow cytometry were performed. Histological examination revealed very few mesenchymal cells in the stromal layer, and a cellular yield of AECs of 10 × 10(6)/gram of digested tissue was achieved. AECs readily attached to plastic culture dishes displaying typical cuboidal morphology and, although their proliferative capacity decreased to the fifth passage, AECs showed a mean doubling time of 24.77 ± 6 h and a mean frequency of one fibroblast colony-forming unit (CFU-F) for every 116.75 plated cells. AECs expressed mesenchymal stem cell (MSC) mRNA markers (CD29, CD166, CD90, CD73, CD117) and pluripotent markers (Nanog and Oct 4), whereas they were negative for CD34 and MHCII. Mesodermic, ectodermic, and endodermic differentiation was confirmed by staining and expression of specific markers. We conclude that porcine amniotic membrane can provide an attractive source of stem cells that may be a useful tool for biomedical research.

  9. Cost-effectiveness models for chronic obstructive pulmonary disease : cross-model comparison of hypothetical treatment scenarios

    NARCIS (Netherlands)

    Hoogendoorn, Martine; Feenstra, Talitha L; Asukai, Yumi; Borg, Sixten; Hansen, Ryan N; Jansson, Sven-Arne; Samyshkin, Yevgeniy; Wacker, Margarethe; Briggs, Andrew H; Lloyd, Adam; Sullivan, Sean D; Rutten-van Mölken, Maureen P M H

    2014-01-01

    OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. METHODS: COPD modeling groups simulated four hypothetical inte

  10. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

    Science.gov (United States)

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  11. Stiripentol in acute/chronic efficacy tests in monkey model.

    Science.gov (United States)

    Lockard, J S; Levy, R H; Rhodes, P H; Moore, D F

    1985-01-01

    Acute and chronic efficacy tests of stiripentol (4,4-dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol) were conducted in alumina-gel rhesus monkeys. In the acute study (n = 6), discrete serial seizures precipitated by 150 mg/kg of 4-deoxypyridoxine hydrochloride were challenged by intravenous administration of stiripentol and the data compared with those obtained with valproate similarly tested in other monkeys (reported here) and with those from four other standard anticonvulsants (phenytoin, carbamazepine, phenobarbital, and diazepam--data published previously). In the acute challenge (Study 1), stiripentol performed comparably to valproate by delaying the onset of seizures but not eliminating them as did the other four drugs. In two separate chronic studies (at different doses, n = 6 each), stiripentol was given every 4 h by gastric catheter for 4 weeks, preceded and followed by 4 weeks of baseline. In these studies, stiripentol significantly reduced EEG interictal spike rates at mean plasma concentrations from 20 to 27 micrograms/ml in Study 2 and 11 to 14 micrograms/ml in Study 3. From these results, and those evinced in other studies, it appears that stiripentol should be evaluated for absence epilepsy and possible synergistic effects in polytherapy.

  12. The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes,and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and

  13. Model Construction for the Intention to Use Telecare in Patients with Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Jui-Chen Huang

    2013-01-01

    Full Text Available Objective. This study chose patients with chronic diseases as study subjects to investigate their intention to use telecare. Methods. A large medical institute in Taiwan was used as the sample unit. Patients older than 20 years, who had chronic diseases, were sampled by convenience sampling and surveyed with a structural questionnaire, and a total of 500 valid questionnaires were collected. Model construction was based on the Health Belief Model. The reliability and validity of the measurement model were tested using confirmatory factor analysis (CFA, and the causal model was explained by structural equation modeling (SEM. Results. The priority should be on promoting the perceived benefits of telecare, with a secondary focus on the external cues to action, such as promoting the influences of important people on the patients. Conclusion. The findings demonstrated that patients with chronic diseases use telecare differently from the general public. To promote the use and acceptance of telecare in patients with chronic diseases, technology developers should prioritize the promotion of the usefulness of telecare. In addition, policy makers can strengthen the marketing from media and medical personnel, in order to increase the acceptance of telecare by patients with chronic diseases.

  14. Establishment of a miniature porcine model for controlled cardiac deceased donor%建立小型猪可控型心脏死亡模型

    Institute of Scientific and Technical Information of China (English)

    毕见龙; 蔡明; 袁清; 邹凡; 和安

    2015-01-01

    Objective To establish a type of porcine model for controlled Cardiac Deceased Donor.Method Using the wuzhishan miniature pig 2 ~ 4 months of age.After intravenous general anesthesia and respiratory,after open heart surgery to produce myocardial infarction model,to heartbeat stop completely,stop breathing machine and drug support,so we established a miniature pig cardiac death donor model.Record during the heart rate,systolic pressure,diastolic blood pressure,central venous blood pressure,blood oxygen saturation and regularly take on blood gas analysis.Before cardiac arrest,monitoring hemodynamic,blood gas analysis,and the time of death before the circulatory failure.After cardiac arrest respectively 0 min,15 min and 30 min,perfusion for donor organs (liver/kidney),get the pig's liver/kidney in the different time of the groups,observed the pathological changes of liver/kidney tissues by HE staining.Result The heartbeat stop completely occurs 7 ± 0.17 minutes after left descending coronary artery ligation and cease of assisted respiration in the different groups,systolic pressure,diastolic blood pressure,central venous pressure,blood oxygen saturation,CO2 partial pressure changed significantly;Immediately after cardiac arrest for compared group (0 min),schemia-reperfusion that group of 15 min after cardiac arrest injury is obvious,ischemia-reperfusion that group of 30 min after cardiac arrest injury is further.Conclusion Miniature pig donor model obtained in this method respiratory cycle failure stability,can be controlled,no adverse drug reactions,the organ ischemia-reperfusion injury caused by repetitive is better.%目的 建立一种小型猪可控型心脏死亡供者模型.方法 采用2~4个月龄的五指山小型猪.静脉及呼吸全身麻醉后,开胸手术制作心肌梗死模型,使供猪出现心脏骤停,同时中断呼吸机及药物支持,由此制备可控型心脏死亡模型.在心脏停搏前后监测循环衰竭前血流动力学、血液

  15. An integrated chronic disease management model: a diagonal approach to health system strengthening in South Africa.

    Science.gov (United States)

    Mahomed, Ozayr Haroon; Asmall, Shaidah; Freeman, Melvyn

    2014-11-01

    The integrated chronic disease management model provides a systematic framework for creating a fundamental change in the orientation of the health system. This model adopts a diagonal approach to health system strengthening by establishing a service-linked base to training, supervision, and the opportunity to try out, assess, and implement integrated interventions.

  16. Prepubertal chronic stress and ketamine administration to rats as a neurodevelopmental model of schizophrenia symptomatology.

    Science.gov (United States)

    Ram, Edward; Raphaeli, Shani; Avital, Avi

    2013-11-01

    Increased vulnerability to psychiatric disorders, such as schizophrenia, has been associated with higher levels of stress. In the early development of the central nervous system, changes in function of glutamatergic N-Methyl-D-aspartate (NMDA) receptors can possibly result in the development of psychosis, cognitive impairment and emotional dysfunction in adulthood. Thus, in this study we examined the behavioural consequences of the exposure of male rats to chronic stress (postnatal days 30-60) and ketamine administration (postnatal days 41-45); both during a sensitive developmental time window. We found that the locomotor activity of both ketamine and ketamine+chronic stress groups was significantly higher compared with that of the control rats. In contrast, the locomotor activity of the chronic stress group was significantly lower compared with all other groups. Examining anhedonia in the sucrose preference test we found a significantly decreased sucrose intake in both ketamine+chronic stress and the chronic stress groups compared with the control rats. No significant differences were observed in sucrose intake between the control and the ketamine group. The object recognition test revealed that the attention to the novel object was significantly impaired in the ketamine+chronic stress group. Similarly, the ketamine+chronic stress group showed the poorest learning ability in the eight-arm radial maze, starting on the 8th day. Finally, throughout the different pre-pulse intensities, the ketamine+chronic stress group showed impaired PPI compared with all other groups. The results indicate that the combination of prepubertal onset of chronic stress and ketamine may serve as a valid novel animal model for schizophrenia-like symptoms.

  17. The Relevance of Value Net Integrator and Shared Infrastructure Business Models in Managing Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Susan Lambert

    2005-11-01

    Full Text Available There is widespread support for chronic condition management (CCM programs that require a multi-disciplinary, care-team approach. Implementation of such programs represents a paradigm shift in primary care service delivery and has significant resource implications for the general practice. Integral to the widespread uptake of care-team based CCM is information collection, storage and dissemination amongst the care-team members. This paper looks to ebusiness models for assistance in understanding the requirements of general practitioners (GPs in providing multi-disciplinary team care to patients with chronic conditions. The role required of GPs in chronic condition management is compared to that of a value net integrator. The essential characteristics of value net integrators are identified and compared to those of GPs providing multi-disciplinary team care to patients with chronic conditions. It is further suggested that a shared infrastructure is required.

  18. Utility of 11C-methionine and 11C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model

    DEFF Research Database (Denmark)

    Afzelius, Pia; Alstrup, Aage Ko; Schønheyder, Henrik C

    2016-01-01

    The aim of this study was to compare (11)C-methionine and (11)C-donepezil positron emission tomography (PET) with (111)In-labeled leukocyte and (99m) Tc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and (18)F-fluorodeoxyglucose ((18)F...... in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, (11)C-methionine and (11)C-donepezil PET, (99m) Tc-DPD and (111)In-labelled leukocytes scintigraphy, and (18)F-FDG PET. This was followed by necropsy of the pigs and gross......-methionine in 79%, (11)C-donepezil in 58%, and (99m) Tc-DPD in none. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT and (11)C-methionine in marking infectious lesions....

  19. Utility of (11)C-methionine and (11)C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model

    DEFF Research Database (Denmark)

    Afzelius, Pia; Alstrup, Aage Ko; Schønheyder, Henrik C;

    2016-01-01

    The aim of this study was to compare (11)C-methionine and (11)C-donepezil positron emission tomography (PET) with (111)In-labeled leukocyte and (99m) Tc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and (18)F-fluorodeoxyglucose ((18)F...... in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, (11)C-methionine and (11)C-donepezil PET, (99m) Tc-DPD and (111)In-labelled leukocytes scintigraphy, and (18)F-FDG PET. This was followed by necropsy of the pigs and gross......-methionine in 79%, (11)C-donepezil in 58%, and (99m) Tc-DPD in none. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT and (11)C-methionine in marking infectious lesions....

  20. Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models.

    Science.gov (United States)

    Andrus, B M; Blizinsky, K; Vedell, P T; Dennis, K; Shukla, P K; Schaffer, D J; Radulovic, J; Churchill, G A; Redei, E E

    2012-01-01

    The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar-Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.

  1. Neuroprotective Effect against Alzheimer's Disease of Porcine Brain Extract

    Directory of Open Access Journals (Sweden)

    Wipawee Thukham-Mee

    2012-01-01

    Full Text Available Problem statement: Despite the increasing importance of Alzheimer’s disease, no effective therapeutic strategy is available. Therefore, neuroprotective strategy is still required. Recent findings show that numerous substances possessing antioxidant can improve neurodegeneration and memory impairment. Based on the antioxidant effect and its reputation to serve as brain tonic in traditional folklore, we hypothesized that porcine brain extract could mitigate neurodegeneration and memory impairment. Therefore, this study was set up to determine the effect of porcine brain extract on memory impairment and neurodegeneration in animal models of Alzheimer’s disease. Approach: Male Wistar rats (180-220 g had been orally given porcine brain extract at doses of 0.5 and 2.5 mg kg-1 BW for a period of 4 weeks before and 1 week after the induction of cognitive deficit condition as those found in early phase of Alzheimer’s disease via the intraventricular injection of AF64A, a cholinotoxin. Rats were assessed the spatial memory using Morris water maze test. Then, they were determined neuron density in hippocampus using histological techniques. Moreover, the assessment of acetylcholinesterase (AChE activity and malondialdehyde (MDA level in hippocampus were also performed. Results: It was found that both doses of porcine brain extract could enhance memory, neuron and cholinergic neuron density in all subregions of hippocampus. In addition, the decreased AChE and MDA were also observed. Therefore, our results suggested that the possible underlying mechanism of the extract might occur partly via the decrease in oxidative stress marker, MDA and AChE. Conclusion: This study clearly demonstrates that porcine brain extract can protect against memory impairment and neurodegeneration in animal model of Alzheimer’s disease. Therefore, it should be serve as the potential food supplement or adjuvant therapy against Alzheimer’s disease and other age-related cognitive

  2. Effects of Modeling and Reinforcement on Adult Chronic Schizophrenics

    Science.gov (United States)

    Olson, R. Paul

    1971-01-01

    This study confirmed two general predictions: (1) the model contributes to new learning; and (2) neither the model nor reinforcement of the model adds significantly to motivation, beyond the effect that can be attributed to reinforcement of the subject himself. (Author/CG)

  3. Effects of Porcine Pancreatic Enzymes on the Pancreas of Hamsters. Part 2: Carcinogenesis Studies

    OpenAIRE

    2012-01-01

    Context Our previous study suggested that porcine pancreatic extract in hamsters with peripheral insulin resistance, normalizes insulin output, islet size and pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic cancer cells in nude mice. Objective To examine the potential value of the porcine pancreatic extract in controlling pancreatic carcinogenesis in this model, the present experiment was performed. Design Hamsters were fed a high fat diet and four wee...

  4. Chronic pain and PTSD: the Perpetual Avoidance Model and its treatment implications.

    Science.gov (United States)

    Liedl, Alexandra; Knaevelsrud, Christine

    2008-01-01

    Posttraumatic Stress Disorder (PTSD) and chronic pain are frequently seen in the aftermath of a traumatic experience. Torture survivors have an increased risk to suffer from these two disorders. Although many studies report high comorbidity,there is still insufficient knowledge on the mechanisms of the development and maintenance of PTSD and chronic pain. After providing an overview of the current literature concerning the comorbidity of these two disorders, we will present the "Perpetual Avoidance Model" (PAM). This model provides an explanation of the reciprocal maintenance of both disorders and offers treatment implications.

  5. Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2

    DEFF Research Database (Denmark)

    Hasslung, F.; Wallgren, P.; Hansen, Anne-Sofie Ladekjær;

    2005-01-01

    An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS). A Swed......An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS...

  6. Partnerships to provide care and medicine for chronic diseases: a model for emerging markets.

    Science.gov (United States)

    Goroff, Michael; Reich, Michael R

    2010-12-01

    The challenge of expanding access to treatment and medicine for chronic diseases in emerging markets is both a public health imperative and a commercial opportunity. Cross-sector partnerships-involving a pharmaceutical manufacturer; a local health care provider; and other private, public, and nonprofit entities-could address this challenge. Such partnerships would provide integrated, comprehensive care and medicines for a specific chronic disease, with medicines directly supplied to the partnership at preferential prices by the manufacturer. The model discussed here requires additional specification, using real numbers and specific contexts, to assess its feasibility. Still, we believe that this model has the potential for public health and private business to cooperate in addressing the rising problem of chronic diseases in emerging markets.

  7. Brief but chronic increase in allopregnanolone cause accelerated AD pathology differently in two mouse models.

    Science.gov (United States)

    Bengtsson, Sara K; Johansson, Maja; Backstrom, Torbjorn; Nitsch, Roger M; Wang, Mingde

    2013-01-01

    Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer's disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Aβ in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels.

  8. Establishment of a chronic left ventricular aneurysm model in rabbit

    Institute of Scientific and Technical Information of China (English)

    Cang-Song XIAO; Chang-Qing GAO; Li-Bing LI; Yao WANG; Tao ZHAO; Wei-Hua YE; Chong-Lei REN; Zhi-Yong LIU; Yang WU

    2014-01-01

    Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm (LVA) in rabbits. Methods Acute myocardial infarction (AMI) was induced in 35 rabbits via concomitant ligation of the left anterior descending (LAD) coronary artery and the circumflex (Cx) branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure (LVESP) and diastolic pressure (LVEDP) were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum (IVS) and the left ventricular posterior wall (LVPW) left ventricular end diastolic volume (LVEDV) and systolic volume (LVESV), and ejection fraction (EF) were recorded by echo-cardiography. Results Thirty one (88.6%) rabbits survived myocardial infarction and 26 of them developed aneurysm (83.9%). The mean area of aneurysm was 33.4% ± 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle (LV) that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%±2.4%which involves the apex, anterior wall and lateral wall of the LV.

  9. Interaction between Campylobacter and intestinal epithelial cells leads to a different proinflammatory response in human and porcine host.

    Science.gov (United States)

    Aguilar, Carmen; Jiménez-Marín, Ángeles; Martins, Rodrigo Prado; Garrido, Juan J

    2014-11-15

    Campylobacter jejuni and Campylobacter coli are recognized as the leading causes of human diarrheal disease throughout the development world. Unlike human beings, gastrointestinal tract of pigs are frequently colonized by Campylobacter to a high level in a commensal manner. The aim of this study was to identify the differences underlying the divergent outcome following Campylobacter challenge in porcine versus human host. In order to address this, a comparative in vitro infection model was combined with microscopy, gentamicin protection assay, ELISA and quantitative PCR techniques. Invasion assays revealed that Campylobacter invaded human cells up to 10-fold more than porcine cells (pCampylobacter in human epithelial cell at early times of infection, whereas a very reduced cytokine gene expression was detected in porcine epithelial cells. These data indicate that Campylobacter fails to invade porcine cells compared to human cells, and this leads to a lack of proinflammatory response induction, probably due to its pathogenic or commensal behavior in human and porcine host, respectively.

  10. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    Science.gov (United States)

    Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

    2014-01-01

    Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

  11. A neural model for chronic pain and pain relief by extracorporeal shock wave treatment.

    Science.gov (United States)

    Wess, Othmar J

    2008-12-01

    The paper develops a new theory of chronic pain and pain relief by extracorporeal shock wave treatment. Chronic pain without underlying anatomical disorder is looked at as a pathological control function of memory. Conditioned reflexes are considered to be engraved memory traces linking sensory input of afferent signals with motor response of efferent signals. This feature can be described by associative memory functions of the nervous system. Some conditioned reflexes may cause inappropriate or pathological reactions. Consequently, a circulus vitiosus of pain sensation and muscle and/or vessel contraction is generated when pain becomes chronic (pain spiral). The key feature is a dedicated engram responsible for a pathological (painful) reaction. The pain memory may be explained by the concept of a holographic memory model published by several authors. According to this model it is shown how nervous systems may generate and recall memory contents. The paper shows how extracorporeal shock wave treatment may reorganize pathologic memory traces, thus giving cause to real and permanent pain relief. In a generalized manner, the idea of associative memory functions may help in the understanding of conditioning as a learning process and explain extracorporeal shock wave application as an efficient treatment concept for chronic pain. This concept may open the door for new treatment approaches to chronic pain and several other disorders of the nervous system.

  12. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.

    Science.gov (United States)

    Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J; Murphy, Stephen F; Thumbikat, Praveen

    2014-07-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.

  13. Developing an active implementation model for a chronic disease management program

    Directory of Open Access Journals (Sweden)

    Margrethe Smidth

    2013-06-01

    Full Text Available Background: Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council’s model for complex interventions and the Chronic Care Model.Methods: We used the Medical Research Council’s five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model.Results: The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council’s model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active

  14. Developing an active implementation model for a chronic disease management program

    Directory of Open Access Journals (Sweden)

    Margrethe Smidth

    2013-06-01

    Full Text Available Background: Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council’s model for complex interventions and the Chronic Care Model.Methods: We used the Medical Research Council’s five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model. Results: The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council’s model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active

  15. A comprehensive examination of the model underlying acceptance and commitment therapy for chronic pain.

    Science.gov (United States)

    Vowles, Kevin E; Sowden, Gail; Ashworth, Julie

    2014-05-01

    The therapeutic model underlying Acceptance and Commitment Therapy (ACT) is reasonably well-established as it applies to chronic pain. Several studies have examined measures of single ACT processes, or subsets of processes, and have almost uniformly indicated reliable relations with patient functioning. To date, however, no study has performed a comprehensive examination of the entire ACT model, including all of its component processes, as it relates to functioning. The present study performed this examination in 274 individuals with chronic pain presenting for an assessment appointment. Participants completed a battery of self-report questionnaires, assessing multiple aspects of the ACT model, as well as pain intensity, disability, and emotional distress. Initial exploratory factor analyses examined measures of the ACT model and measures of patient functioning separately with each analysis identifying three factors. Next, the fit of a model including ACT processes on the one hand and patient functioning on the other was examined using Structural Equation Modeling. Overall model fit was acceptable and indicated moderate correlations among the ACT processes themselves, as well as significant relations with pain intensity, emotional distress, and disability. These analyses build on the existing literature by providing, to our knowledge, the most comprehensive evaluation of the ACT theoretical model in chronic pain to date.

  16. Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.

    Science.gov (United States)

    Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V; Arbeev, Konstantin G; Akleyev, Alexander V; Yashin, Anatoly I

    2011-05-01

    A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).

  17. Multidisciplinary Rehabilitation Treatment of Patients With Chronic Low Back Pain: A Prognostic Model for Its Outcome

    NARCIS (Netherlands)

    Hulst, van der Marije; Vollenbroek-Hutten, Miriam M.R.; Groothuis-Oudshoorn, Karin G.M.; Hermens, Hermie J.

    2008-01-01

    Objectives: (1) To determine if treatment outcome in chronic low back pain can be predicted by a predefined multivariate prognostic model based on consistent predictors from the literature and (2) to explore the value of potentially prognostic factors further. Methods: Data were derived from a rand

  18. Can the common-sense model predict adherence in chronically ill patients? A meta-analysis

    NARCIS (Netherlands)

    K. Brandes; B. Mullan

    2013-01-01

    The aim of this meta-analysis was to explore whether mental representations, derived from the common-sense model of illness representations (CSM), were able to predict adherence in chronically ill patients. Electronic databases were searched for studies that used the CSM and measured adherence behav

  19. Remote patient management: technology-enabled innovation and evolving business models for chronic disease care.

    Science.gov (United States)

    Coye, Molly Joel; Haselkorn, Ateret; DeMello, Steven

    2009-01-01

    Remote patient management (RPM) is a transformative technology that improves chronic care management while reducing net spending for chronic disease. Broadly deployed within the Veterans Health Administration and in many small trials elsewhere, RPM has been shown to support patient self-management, shift responsibilities to non-clinical providers, and reduce the use of emergency department and hospital services. Because transformative technologies offer major opportunities to advance national goals of improved quality and efficiency in health care, it is important to understand their evolution, the experiences of early adopters, and the business models that may support their deployment.

  20. Protective Action of Acupuncture and Moxibustion on Gastric Mucosa in Model Rats with Chronic Atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    高希言; 饶红; 王燕; 孟丹; 魏玉龙

    2005-01-01

    Objective: To probe the mechanism of acupuncture and moxibustion in atrophic gastritis so as to provide a basis for clinical treatment. Method: Observe the effects of acupuncture and moxibustion at the points of Zusanli, Zhongwan and Tianshu on gastric mucosa in model rats with chronic atrophic gastritis. Results:Acupuncture and moxibustion can increase the contents of PGE2α, PGF2α and cAMP, and decrease the content of cGMP in the tissue of gastric mucosa. Conclusion: Acupuncture and moxibustion shows cytoprotection on gastric mucosa, so it is an effective method for treating chronic atrophic gastritis.

  1. Laser-induced thermotherapy (LITT) - evaluation of a miniaturised applicator and implementation in a 1.0-T high-field open MRI applying a porcine liver model

    Energy Technology Data Exchange (ETDEWEB)

    Streitparth, Florian; Knobloch, Gesine; Rump, J.; Wonneberger, Uta; Hamm, Bernd; Teichgraeber, Ulf [Charite, Humboldt-Universitaet zu Berlin, Department of Radiology, Berlin (Germany); Balmert, Dirk [Somatex Medical Technologies GmbH, Teltow (Germany); Chopra, Sascha [Charite, Humboldt-University, Department of General, Visceral, and Transplantation Surgery, Berlin (Germany); Philipp, Carsten [Elisabeth Klinik, Department of Laser Medicine, Berlin (Germany)

    2010-11-15

    To evaluate the feasibility and safety of a novel LITT applicator for thermal ablation of liver malignancies in 1.0-T high-field open MRI. A miniaturised 6-F double-tubed protective catheter with a closed cooling circuit was used with a flexible laser fibre, connected to a 1,064-nm Nd:YAG laser and evaluated in non-perfused porcine livers (18-30 W for 10-20 min, 2-W and 2-min increments; n = 210/applicator) in reference to an established 9-F system. As a proof of concept, MR-guided LITT was performed in two healthy domestic pigs in high-field open MRI. Ex-vivo, the coagulation volumes induced by the 6-F system with maximum applicable power of 24 W for 20 min (33.0 {+-} 4.4 cm{sup 3}) did not differ significantly from those set with the 9-F system at 30 W for 20 min (35.8 {+-} 4.9 cm{sup 3}) (p = 0.73). A flow-rate of 15 ml/min of the cooling saline solution was sufficient. MR navigation and thermometry were feasible. The miniaturised 6-F applicator can create comparable coagulation sizes to those of the 9-F system. Applicator guidance and online-thermometry in high-field open MRI are feasible. (orig.)

  2. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  3. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Science.gov (United States)

    Su, Zhengxiu; Zhu, Hongguo; Zhang, Menghuan; Wang, Liangliang; He, Hanchang; Jiang, Shaoling; Hou, Fan Fan; Li, Aiqing

    2014-01-01

    Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  4. Prediction of chronic damage in systemic lupus erythematosus by using machine-learning models

    Science.gov (United States)

    Perricone, Carlo; Galvan, Giulio; Morelli, Francesco; Vicente, Luis Nunes; Leccese, Ilaria; Massaro, Laura; Cipriano, Enrica; Spinelli, Francesca Romana; Alessandri, Cristiano; Valesini, Guido; Conti, Fabrizio

    2017-01-01

    Objective The increased survival in Systemic Lupus Erythematosus (SLE) patients implies the development of chronic damage, occurring in up to 50% of cases. Its prevention is a major goal in the SLE management. We aimed at predicting chronic damage in a large monocentric SLE cohort by using neural networks. Methods We enrolled 413 SLE patients (M/F 30/383; mean age ± SD 46.3±11.9 years; mean disease duration ± SD 174.6 ± 112.1 months). Chronic damage was assessed by the SLICC/ACR Damage Index (SDI). We applied Recurrent Neural Networks (RNNs) as a machine-learning model to predict the risk of chronic damage. The clinical data sequences registered for each patient during the follow-up were used for building and testing the RNNs. Results At the first visit in the Lupus Clinic, 35.8% of patients had an SDI≥1. For the RNN model, two groups of patients were analyzed: patients with SDI = 0 at the baseline, developing damage during the follow-up (N = 38), and patients without damage (SDI = 0). We created a mathematical model with an AUC value of 0.77, able to predict damage development. A threshold value of 0.35 (sensitivity 0.74, specificity 0.76) seemed able to identify patients at risk to develop damage. Conclusion We applied RNNs to identify a prediction model for SLE chronic damage. The use of the longitudinal data from the Sapienza Lupus Cohort, including laboratory and clinical items, resulted able to construct a mathematical model, potentially identifying patients at risk to develop damage. PMID:28329014

  5. Effect of Electro-acupuncture on Rat Joint Patho-morphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    张幼美; 胡玲; 唐纯志; 曹伟

    2003-01-01

    Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund's adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats. These pathological changes were significantly improved after treatment, and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group. Conclusion: High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant arthritis rat models.

  6. Effect of Electro—acupuncture on Rat Joint Pathomorphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    ZHANGYou-mei; HULing; 等

    2003-01-01

    Objective:To study the effect of electro-acupuncture(EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis.Methods:The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freunds adjuvant to the left hind sole.Forty Wistar rats were randomly divided into the model group,the low frequency(2Hz) EA group,the high frequency EA(100Hz)group and the body acupuncture group.After being modeled except the model group,the other three groups were treated with EA or body acupuncture in Yanglingquan points(bilater-al)for 3weeks,the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin,sectioning and staining with HE.Results:Obvious inflammatory cell infiltration,loosened synovial tissue,damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.These pathologi-cal changes were significantly improved after treatment,and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group.Conclusion:High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant ar-thritis rat models.

  7. Perforation forces of the intact porcine anterior lens capsule.

    Science.gov (United States)

    Ullrich, Franziska; Lussi, Jonas; Felekis, Dimitrios; Michels, Stephan; Petruska, Andrew J; Nelson, Bradley J

    2016-09-01

    During the first step of cataract surgery, the lens capsule is perforated and a circular hole is created with a sharp instrument, a procedure called capsulorhexis. To develop automated systems that can assist ophthalmologists during capsulorhexis, the forces required must be quantified. This study investigates perforation forces of the central anterior lens capsule in porcine eyes, which are used as a conservative model for the human eye. A micro-mechanical characterisation method is presented that measures capsular bag perforation forces with a high precision positioning and high-resolution force sensing system. The force during perforation of the anterior lens capsule was measured with various sized needles and indentation speeds and is found to be 15-35mN. A bio-mechanical model is identified that describes an exponential correlation between indentation force and depth, indicating strain hardening behaviour of the porcine anterior lens capsule.

  8. Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Agostino Colli; Alice Colucci; Silvia Paggi; Mirella Fraquelli; Sara Massironi; Marco Andreoletti; Vittorio Michela; Dario Conte

    2005-01-01

    AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV)infection.METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio,platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%,the model defined four levels of post-test probability of severe fibrosis/cirrhosis: 90% (almost absolute).The predicted probabilities were compared with the observed patients' distribution according to the histology (METAVIR).RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%)or low (75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.

  9. The chronic mild stress (CMS) model of depression: History, evaluation and usage.

    Science.gov (United States)

    Willner, Paul

    2017-02-01

    Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

  10. Use of small intestine submucosa in a rat model of acute and chronic rotator cuff tear.

    Science.gov (United States)

    Perry, Stephanie M; Gupta, Rishi R; Van Kleunen, Jonathan; Ramsey, Matthew L; Soslowsky, Louis J; Glaser, David L

    2007-01-01

    Augmentation materials for rotator cuff tears, such as small intestine submucosa (SIS), have been used with the goal of improving outcome. Knowledge is limited on the use of SIS in animal models of acute and chronic rotator cuff tears. We hypothesized that the use of SIS in the surgical management of full thickness supraspinatus tears would improve histologic and biomechanical properties. Results show temporal improvements in several histologic parameters. Both acute and chronic injuries repaired with SIS have similar and increased mechanical properties respectively, compared to those repaired without SIS. In general, acute repairs with SIS were comparable to acute repairs without SIS. In chronic repairs, the use of SIS significantly reduced the cross sectional area of the healing tendon and increased the modulus. These results provide information on the use of SIS for rotator cuff repairs.

  11. Different microRNA profiles in chronic epilepsy versus acute seizure mouse models.

    Science.gov (United States)

    Kretschmann, Anita; Danis, Benedicte; Andonovic, Lidija; Abnaof, Khalid; van Rikxoort, Marijke; Siegel, Franziska; Mazzuferi, Manuela; Godard, Patrice; Hanon, Etienne; Fröhlich, Holger; Kaminski, Rafal M; Foerch, Patrik; Pfeifer, Alexander

    2015-02-01

    Epilepsy affects around 50 million people worldwide, and in about 65% of patients, the etiology of disease is unknown. MicroRNAs are small non-coding RNAs that have been suggested to play a role in the pathophysiology of epilepsy. Here, we compared microRNA expression patterns in the hippocampus using two chronic models of epilepsy characterised by recurrent spontaneous seizures (pilocarpine and self-sustained status epilepticus (SSSE)) and an acute 6-Hz seizure model. The vast majority of microRNAs deregulated in the acute model exhibited increased expression with 146 microRNAs up-regulated within 6 h after a single seizure. In contrast, in the chronic models, the number of up-regulated microRNAs was similar to the number of down-regulated microRNAs. Three microRNAs-miR-142-5p, miR-331-3p and miR-30a-5p-were commonly deregulated in all three models. However, there is a clear overlap of differentially expressed microRNAs within the chronic models with 36 and 15 microRNAs co-regulated at 24 h and at 28 days following status epilepticus, respectively. Pathway analysis revealed that the altered microRNAs are associated with inflammation, innate immunity and cell cycle regulation. Taken together, the identified microRNAs and the pathways they modulate might represent candidates for novel molecular approaches for the treatment of patients with epilepsy.

  12. Prognostic factors for chronic severe hepatitis and construction of a prognostic model

    Institute of Scientific and Technical Information of China (English)

    Qian Li; Gui-Yu Yuan; Ke-Cheng Tang; Guo-Wang Liu; Rui Wang; Wu-Kui Cao

    2008-01-01

    BACKGROUND:Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model. METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis. RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were signiifcantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P)=1.573×Age+1.338× HE-1.608×CHO+0.011×Cr-0.109×Na+1.298×INR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score. CONCLUSIONS:Multivariate analysis excels univariate anlysis in the prognosis of chronic severe hepatitis, and the regression model is of signiifcant value in the prognosis of this disease.

  13. MicroRNA-199a-5p Affects Porcine Preadipocyte Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Xin-E Shi

    2014-05-01

    Full Text Available MicroRNAs (miRNAs, a class of small non-coding RNAs, have emerged as novel and potent regulators of adipogenesis. However, few miRNAs have been fully investigated in porcine adipogenesis, given the fact that pig is not only an apropos model of human obesity research, but also a staple meat source of human diet. In this study, we showed that miRNA-199a-5p is highly expressed in porcine subcutaneous fat deposits compared to several other tissue types and organs measured alongside. Overexpression of miR-199a-5p in porcine preadipocytes significantly promoted cell proliferation while attenuating the lipid deposition in porcine adipocytes. By target gene prediction and experimental validation, we demonstrated that caveolin-1 (Cav-1 may be a bona fide target of miR-199a-5p in porcine adipocytes, accounting for some of miR-199a-5p’s functions. Taken together, our data established a role of miR-199a-5p in porcine preadipocyte proliferation and differentiation, which is at least partially played by downregulating Cav-1.

  14. A novel inexpensive murine model of oral chronic digitalization.

    Science.gov (United States)

    Helber, Izo; Kanashiro, Rosemeire M; Alarcon, Ernesto A; Antonio, Ednei L; Tucci, Paulo J F

    2004-01-01

    A novel inexpensive murine model of oral administration of digitoxin (100 micro g/kg per day) added to routine chow is described. Serum digitoxin levels achieved after oral (n = 5; 116 +/- 14 ng/mL) and subcutaneous (n = 5; 124 +/- 11 ng/mL) administration were similar. A significant increase in the maximal left ventricular pressure rise of treated (n = 9) compared with control (n = 6) rats (dP/dt: 8956 +/- 233 vs 7980 +/- 234 mmHg/s, respectively; P = 0.01) characterized the positive inotropic action of digitoxin. In addition, no differences were observed in treated compared with control rats with regard to the electrocardiogram and systolic and diastolic left ventricular pressures.

  15. Adjustment and Characterization of an Original Model of Chronic Ischemic Heart Failure in Pig

    Directory of Open Access Journals (Sweden)

    Laurent Barandon

    2010-01-01

    Full Text Available We present and characterize an original experimental model to create a chronic ischemic heart failure in pig. Two ameroid constrictors were placed around the LAD and the circumflex artery. Two months after surgery, pigs presented a poor LV function associated with a severe mitral valve insufficiency. Echocardiography analysis showed substantial anomalies in radial and circumferential deformations, both on the anterior and lateral surface of the heart. These anomalies in function were coupled with anomalies of perfusion observed in echocardiography after injection of contrast medium. No demonstration of myocardial infarction was observed with histological analysis. Our findings suggest that we were able to create and to stabilize a chronic ischemic heart failure model in the pig. This model represents a useful tool for the development of new medical or surgical treatment in this field.

  16. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

    Science.gov (United States)

    Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

    2016-04-01

    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

  17. Can the common-sense model predict adherence in chronically ill patients? A meta-analysis.

    Science.gov (United States)

    Brandes, Kim; Mullan, Barbara

    2014-01-01

    The aim of this meta-analysis was to explore whether mental representations, derived from the common-sense model of illness representations (CSM), were able to predict adherence in chronically ill patients. Electronic databases were searched for studies that used the CSM and measured adherence behaviour in chronically ill patients. Correlations from the included articles were meta-analysed using a random-size effect model. A moderation analysis was conducted for the type of adherence behaviour. The effect sizes for the different mental representations and adherence constructs ranged from -0.02 to 0.12. Further analyses showed that the relationship between the mental representations and adherence did not differ by the type of adherence behaviour. The low-effect sizes indicate that the relationships between the different mental representations of the CSM and adherence are very weak. Therefore, the CSM may not be the most appropriate model to use in predictive studies of adherence.

  18. Identification and examination of a novel 9-bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid-acute lung injury model.

    Science.gov (United States)

    Zhang, Yuebo; Zhang, Longchao; Wang, Ligang; Qiao, Lijuan; Liang, Jing; Yan, Hua; Zhao, Kebin; Liu, Xin; Wang, Lixian

    2015-06-01

    The pulmonary surfactant-associated protein (SFTPA1, SP-A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR-single-strand conformation polymorphism method, a novel 9-bp nucleotide insertion (+) or deletion (-) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (-/-, +/- and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)-ALI model by 1-h and 3-h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9-bp indel polymorphism (P polymorphism causing altered expression of the gene. The individuals with the -/- genotype showed lower lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease-resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies.

  19. Individualizing Opioid Use Disorder (OUD Treatment: Time to Fully Embrace a Chronic Disease Model

    Directory of Open Access Journals (Sweden)

    Richard Gustin

    2015-02-01

    Full Text Available The current opioid epidemic in the United States is changing our perceptions of the face of addiction. Opioid Use Disorder (OUD has become pervasive and is affecting all ethnicities, races, socioeconomic classes, the young and the old. In 2015, 46 people will lose their life each day to a chronic brain disease that is going unnoticed and undertreated. Over the last five decades, numerous scientific and clinical breakthroughs have allowed for a better understanding of the mechanisms underlying addiction, and the development of medications that can help support a patient’s long-term recovery. All of those that have contributed to these advancements have aided in redefining addiction as a primary, chronic disease of the brain reward, motivation, memory and related circuitry; however, our treatment strategies have not necessarily advanced to the same extent as our current understanding of the disease. This commentary will explore how personal philosophies can bias treatments strategies and definitions of treatment success, and prevent adoption of chronic disease treatment models that would significantly improve the quality of life of those suffering with OUD. This is a challenge to consider how our views and stigma can impact a patient’s recovery. We are currently losing a battle with a disease that is taking the lives of 46 individuals daily; it is time to fully embrace a chronic disease model which comprises an integrated pharmacopsychosocial approach for treating the biopsychosocial disorder that is addiction to reverse these trends.

  20. [Research advances in porcine bocavirus].

    Science.gov (United States)

    Zhai, Shao-Lun; Chen, Sheng-Nan; Wei, Wen-Kang

    2012-03-01

    Porcine bocavirus (PBoV) was considered as a new member of the genus Bocavirus of the subfamily Parvovirinae of the family Parvoviridae, which was discovered in Swedish swine herds with postweaning multisystemic wasting syndrome (PMWS) in 2009. At present, as an emerging pathogen, it was paid great attention by researchers at home and abroad. This paper referred to some published literatures and reviewed several aspects of PBoV including its finding, classification, genome structure and replication, epidemiology, associativity with diseases, cultural and diagnostic methods.

  1. Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model

    Directory of Open Access Journals (Sweden)

    Chandan Kishor

    2016-01-01

    Full Text Available Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA are the commonest cause of osteomyelitis. The aim of this study was to evaluate the role of an alternative therapy i.e. application of S. aureus specific bacteriophages in cases of osteomyelitis caused by MRSA in animal model. Methods: Twenty two rabbits were included in this study. The first two rabbits were used to test the safety of phage cocktail while the remaining 20 rabbits were divided into three groups; group A (n=4 to assess the establishment of osteomyelitis; group B (n=4 osteomyelitis developed but therapy started only after six weeks; and group C (n=12 osteomyelitis developed and therapy started after three weeks. Groups B and C rabbits were treated with four doses of cocktail of seven virulent bacteriophages at the interval of 48 h. Comparison between three groups was made on the basis of observation of clinical, radiological, microbiological, and histopathological examinations. Results: Experimental group rabbits recovered from the illness in the subsequent two weeks of the therapy. Appetite and activity of the rabbits improved, local oedema, erythema and induration subsided. There were minimal changes associated with osteomyelitis in X-ray and histopathology also showed no signs of infection with new bone formation. Control B group rabbits also recovered well from the infection. Interpretation & conclusions: The present study shows a potential of phage therapy to treat difficult infections caused by multidrug resistant bacteria.

  2. Treatment of severe chronic hypotonic hyponatremia: a new treatment model

    Directory of Open Access Journals (Sweden)

    Antonio Burgio

    2013-03-01

    Full Text Available Recommended treatment of severe hypotonic hyponatremia is based on the infusion of 3% sodium chloride solution, with a daily correction rate below 10 mEq/L of sodium concentration, according to the Adrogué and Madias formula that includes the current desired change in sodium concentrations. However, such treatment needs close monitoring of the rate of infusion and does not take into account the body weight or age of the patient. This may result in hypercorrection and neurological damage. We made an inverse calculation using the same algorithms of the Adrogué and Madias formula to estimate the number of vials of sodium chloride needed to reach a correction rate of the serum sodium concentration below 0.4 mEq/h, taking into account the body weight and age of the patient. Three tables have been produced, each containing the number of vials to be infused, according to the patient’s age and body weight, the serum sodium concentration, and the rate of correction over 24 h to avoid the risk of brain damage. We propose a new practical model to calculate the need of sodium chloride infusate to safely correct the hyponatremia. The tables make treatment easier to manage in daily clinical practice in a wide range of patient ages and body weights.

  3. Dose-dependent striatal changes in dopaminergic terminals and alpha-synuclein reactivity in a porcine model of progressive Parkinson’s disease

    DEFF Research Database (Denmark)

    Nielsen, Mette Slot; Glud, Andreas Nørgaard; Møller, Arne

    2011-01-01

    of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and here present the neuropatholigical findings. Sixteen Göttingen minipigs were used in the study. Twelve were implanted subcutaneously with infusion pumps for continuous intramuscular chronic MPTP delivery for 11 weeks (4-18 mg MPTP/day, n=12...

  4. Regional multiaxial mechanical properties of the porcine anterior lens capsule.

    Science.gov (United States)

    David, G; Pedrigi, R M; Heistand, M R; Humphrey, J D

    2007-02-01

    The lens capsule of the eye plays fundamental biomechanical roles in both normal physiological processes and clinical interventions. There has been modest attention given to the mechanical properties of this important membrane, however, and prior studies have focused on 1-D analyses of the data. We present results that suggest that the porcine anterior lens capsule has a complex, regionally dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain inverse finite element method to analyze data collected via a new biplane video-based test system, we found that the lens capsule is nearly isotropic (in-plane) near the pole but progressively stiffer in the circumferential compared to the meridional direction as one approaches the equator. Because the porcine capsule is a good model of the young human capsule, there is strong motivation to determine if similar regional variations exist in the human lens capsule for knowledge of such complexities may allow us to improve the design of surgical procedures and implants.

  5. Stability Analysis of a Simplified Yet Complete Model for Chronic Myelegenous Leukemia

    CERN Document Server

    Jauffret, Marie Doumic; Perthame, Benoît

    2009-01-01

    We analyze the asymptotic behavior of a partial differential equation (PDE) model for hematopoiesis. This PDE model is derived from the original agent-based model formulated by (Roeder et al., Nat. Med., 2006), and it describes the progression of blood cell development from the stem cell to the terminally differentiated state. To conduct our analysis, we start with the PDE model of (Kim et al, JTB, 2007), which coincides very well with the simulation results obtained by Roeder et al. We simplify the PDE model to make it amenable to analysis and justify our approximations using numerical simulations. An analysis of the simplified PDE model proves to exhibit very similar properties to those of the original agent-based model, even if for slightly different parameters. Hence, the simplified model is of value in understanding the dynamics of hematopoiesis and of chronic myelogenous leukemia, and it presents the advantage of having fewer parameters, which makes comparison with both experimental data and alternative...

  6. The laparoscopy splenic injury repair: the use of fibrin glue in a heparinized porcine model O reparo de lesão esplênica por laparoscopia: o uso da cola de fibrina em porcos heparinizados

    Directory of Open Access Journals (Sweden)

    Dalmer Faria Freire

    2011-06-01

    Full Text Available PURPOSE: To investigate the effectiveness of fibrin glue (laparoscopic via into promote the hemostasis of a spleen injury on a heparinized porcine model. METHODS: Eighteen Landrace porcine were submitted to laparoscopic spleen injury and randomly distributed: GHA (heparin plus adhesive, GH (heparin without adhesive and GS (Sham - without heparin or adhesive. Ten minutes before the surgical procedures a single IV dose (200UI/kg of heparin sodium was administrated only to groups GHA and GH. In the GHA, adhesive was applied after the mechanical injury and recorded the time until the polymerization and clot formation. RESULTS: No significant differences occurred among the groups (Fisher test considering the weight and surgery time. The blood amount in the abdominal cavity on GH was significantly higher in comparison to the sham group and especially with the GHA (pOBJETIVO: Investigar a eficácia da cola de fibrina (via laparoscópica na hemostasia de uma lesão no baço de porco heparinizado. MÉTODOS: Dezoito suínos Landrace foram submetidos a lesão do baço e distribuídos aleatoriamente: GHA (heparina adesivo, GH (heparina sem adesivo e GS (Sham - sem heparina ou adesivo. Dez minutos antes dos procedimentos uma dose única (200UI/kg de heparina sódica (EV foi administrada nos grupos GHA e GH. A fibrina (GHA foi aplicada após a lesão e registrado o tempo até a polimerização e formação do coágulo. RESULTADOS: Não houve diferenças significativas entre os grupos (teste de Fisher, considerando o peso e o tempo de cirurgia. A quantidade de sangue na cavidade abdominal de GH foi significativamente maior em comparação ao GS e, especialmente, com o GHA (p<0,004. Não foram observadas diferenças significativas na temperatura corporal, frequência cardíaca, débito cardíaco, pressão arterial ou pressão da artéria pulmonar durante o experimento (20 minutos. O tempo de tromboplastina parcial ativada (TTPA foi menor no GHA em relação ao

  7. Measurement of the anisotropic thermal conductivity of the porcine cornea.

    Science.gov (United States)

    Barton, Michael D; Trembly, B Stuart

    2013-10-01

    Accurate thermal models for the cornea of the eye support the development of thermal techniques for reshaping the cornea and other scientific purposes. Heat transfer in the cornea must be quantified accurately so that a thermal treatment does not destroy the endothelial layer, which cannot regenerate, and yet is responsible for maintaining corneal transparency. We developed a custom apparatus to measure the thermal conductivity of ex vivo porcine corneas perpendicular to the surface and applied a commercial apparatus to measure thermal conductivity parallel to the surface. We found that corneal thermal conductivity is 14% anisotropic at the normal state of corneal hydration. Small numbers of ex vivo feline and human corneas had a thermal conductivity perpendicular to the surface that was indistinguishable from the porcine corneas. Aqueous humor from ex vivo porcine, feline, and human eyes had a thermal conductivity nearly equal to that of water. Including the anisotropy of corneal thermal conductivity will improve the predictive power of thermal models of the eye.

  8. Describing and analysing primary health care system support for chronic illness care in Indigenous communities in Australia's Northern Territory – use of the Chronic Care Model

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    Stewart Allison

    2008-05-01

    Full Text Available Abstract Background Indigenous Australians experience disproportionately high prevalence of, and morbidity and mortality from chronic illness such as diabetes, renal disease and cardiovascular disease. Improving the understanding of how Indigenous primary care systems are organised to deliver chronic illness care will inform efforts to improve the quality of care for Indigenous people. Methods This cross-sectional study was conducted in 12 Indigenous communities in Australia's Northern Territory. Using the Chronic Care Model as a framework, we carried out a mail-out survey to collect information on material, financial and human resources relating to chronic illness care in participating health centres. Follow up face-to-face interviews with health centre staff were conducted to identify successes and difficulties in the systems in relation to providing chronic illness care to community members. Results Participating health centres had distinct areas of strength and weakness in each component of systems: 1 organisational influence – strengthened by inclusion of chronic illness goals in business plans, appointment of designated chronic disease coordinators and introduction of external clinical audits, but weakened by lack of training in disease prevention and health promotion and limited access to Medicare funding; 2 community linkages – facilitated by working together with community organisations (e.g. local stores and running community-based programs (e.g. "health week", but detracted by a shortage of staff especially of Aboriginal health workers working in the community; 3 self management – promoted through patient education and goal setting with clients, but impeded by limited focus on family and community-based activities due to understaffing; 4 decision support – facilitated by distribution of clinical guidelines and their integration with daily care, but limited by inadequate access to and support from specialists; 5 delivery system

  9. The phenomenological-existential comprehension of chronic pain: going beyond the standing healthcare models.

    Science.gov (United States)

    Lima, Daniela Dantas; Alves, Vera Lucia Pereira; Turato, Egberto Ribeiro

    2014-01-10

    A distinguishing characteristic of the biomedical model is its compartmentalized view of man. This way of seeing human beings has its origin in Greek thought; it was stated by Descartes and to this day it still considers humans as beings composed of distinct entities combined into a certain form. Because of this observation, one began to believe that the focus of a health treatment could be exclusively on the affected area of the body, without the need to pay attention to patient's subjectivity. By seeing pain as a merely sensory response, this model was not capable of encompassing chronic pain, since the latter is a complex process that can occur independently of tissue damage. As of the second half of the twentieth century, when it became impossible to deny the relationship between psyche and soma, the current understanding of chronic pain emerges: that of chronic pain as an individual experience, the result of a sum of physical, psychological, and social factors that, for this reason, cannot be approached separately from the individual who expresses pain. This understanding has allowed a significant improvement in perspective, emphasizing the characteristic of pain as an individual experience. However, the understanding of chronic pain as a sum of factors corresponds to the current way of seeing the process of falling ill, for its conception holds a Cartesian duality and the positivist premise of a single reality. For phenomenology, on the other hand, the individual in his/her unity is more than a simple sum of parts. Phenomenology sees a human being as an intending entity, in which body, mind, and the world are intertwined and constitute each other mutually, thus establishing the human being's integral functioning. Therefore, a real understanding of the chronic pain process would only be possible from a phenomenological point of view at the experience lived by the individual who expresses and communicates pain.

  10. 高致病性猪繁殖与呼吸综合征传播数学模型研究%Studies on the Mathematical Model of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome

    Institute of Scientific and Technical Information of China (English)

    王光煜

    2011-01-01

    [Objective] The purpose of this paper was to analyze and forecast the transmission trend of porcine reproductive and respiratory syndrome (HP-PRRS) by mathematical model. [Method] The pigs were divided into the susceptible population, the incidence population and the removed. Dynamics model of transmission rate, recover rate and incidence rate were analyzed, and the mathematical model of HP-PRRS was established in transmission process. [Result] Transmission rate β(t), recover rate Υ(t) and incidence rate δ(t) was to conform to the resuits of the actual figures, and the mathematical model of HP-PRRS accorded with the objective law of transmission, [ Conclusion ] This mathematical model was better used to analyze the transmission trend of HP-PRRS.%[目的]分析和预测高致病性猪繁殖与呼吸综合征的流行趋势.[方法]将猪分为3类:易感猪S、发病猪I和退出猪R,拟合传染速率β(t)、恢复率γ(t)和病死率δ(t)的动态模型,建立该病流行的每天病猪数I(t)模型和健康猪数H(t)模型.[结果]通过比较,模型的理论传染速率β(T)、恢复率γ(t)和病死率δ(t)与实际计算结果基本一致,每天病猪数I(t)模型和健康猪数H(t)模型较符合实际.[结论]该数学模型可较好地预测高致病性猪繁殖与呼吸综合征的流行趋势.

  11. Chronic Toxoplasmosis Modulates the Induction of Contact Hypersensitivity by TNCB in Mouse Model.

    Science.gov (United States)

    Yang, Zhaoshou; Ahn, Hye-Jin; Nam, Ho-Woo

    2015-12-01

    Mouse models of chronic toxoplasmosis and atopic dermatitis (AD) were combined to clarify the effect of opportunistic Toxoplasma gondii infection on the development of AD. AD was induced as a chronic contact hypersensitivity (CHS) with repeated challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) on the dorsal skin of mice. TNCB induced skin thickness increases in both normal and toxoplasmic mice. The changing patterns were different from the sigmoidal which saturated at 20 days in normal mice to the convex saturated at 12 days in toxoplasmic mice with the crossing at 18 days. Compared to normal mice, toxoplasmic mice presented CHS more severely in earlier times and then moderately in later times. These data suggest that host immune modification by T. gondii infection enhances CHS in early times of atopic stimulation but soothes the reaction of CHS in later times in mouse model.

  12. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    Science.gov (United States)

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

    2016-01-01

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

  13. The Model of Quality of Life Improvement for Chronic Patients in Community by Using Social Support

    Directory of Open Access Journals (Sweden)

    Amorn Suwannimitr

    2010-01-01

    Full Text Available Problem statement: Caring for a chronically ill-patients is a complex process which require the cooperation and social support to manage a chronic disease. It need an interaction of a large number of actors or collaborations from health care personnel of different organizations. Questions were raised to develop an appropriate intervention and the model of QOL improvement for chronic-patients in the community. Approach: To (1 develop the Quality Of Life (QOL improvement for chronic illness patients in community by using social support program (2 evaluate the effects of the program on perception of illness, severity of illness, benefits and barriers of health promotion, health behaviors, Quality Of Life (QOL and stress level. Participatory Action Research (PAR was used. It was consisted of two phrases. The participants in first phase including with nurses, nutritionist, patients, caregivers, Village Health Volunteers (VHVs and research team. The second phrase was to implement the interventions and evaluation. A total of 10 VHVs and 50 participants who met the inclusion criteria. The intervention composed of 2 main programs; (1The VHVs were trained for 1 month as a comprehensive program to be a healthcare team collaboration. (2The chronically ill-patients received main interventions including self-care education, apply Thai traditional medicine and home visits. Descriptive statistics and t-test were use to evaluate the pre-post intervention. Results: The majority of the participants were female (n = 38,76%, with the mean age of 66.68 years (SD = 17.20, 85% caring by their children and 42.5% by their relatives. Most participants came from low income family (40%. The post test score on each item showed that after intervention, changed scores on all five items (before-after, how ever the changes were statistically significantly (0.05. Conclusion: The findings suggested the set of interventions were effective to improve QOL of chronic patients and it

  14. Novel Totally Laparoscopic Endolumenal Rectal Resection With Transanal Natural Orifice Specimen Extraction (NOSE) Without Rectal Stump Opening: A Modification of Our Recently Published Clean Surgical Technique in a Porcine Model.

    Science.gov (United States)

    Kvasha, Anton; Hadary, Amram; Biswas, Seema; Szvalb, Sergio; Willenz, Udi; Waksman, Igor

    2015-06-01

    Our group has recently described a novel technique for clean endolumenal bowel resection, in which abdominal and transanal approaches were used. In the current study, 2 modifications of this procedure were tested for feasibility in a porcine model. A laparoscopic approach to the peritoneal cavity was employed in rectal mobilization; this was followed by a transanal rectorectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. Once IPT was established, a second ligature was placed around the rectum approximating the proximal and distal resection margins. This was followed by a purse string suture through 2 bowel walls, encircling the shaft of the anvil just proximal to the ligatures. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls distal to the previously placed purse string suture and ligatures. The anastomosis was achieved by applying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. Although, this is a novel and evolving procedure, its minimally invasive nature, as well as aseptic bowel manipulation during endolumenal rectal resection, has the potential to limit the complications associated with abdominal wall incision and surgical site infection.

  15. Biliopancreatic duct injection of ethanol as an experimental model of acute and chronic pancreatitis in rats.

    Science.gov (United States)

    Unal, Ethem; Atalay, Suleyman; Tolan, Huseyin Kerem; Yuksekdag, Sema; Yucel, Metin; Acar, Aylin; Basak, Fatih; Gunes, Pembegul; Bas, Gurhan

    2015-01-01

    In the present study, we described an easily reproducable experimental pancreatits model induced by biliopancreatic duct injection of ethyl alcohol. Seventy Wistar albino rats were divided equally into seven groups randomly: the control group (group 1), acute pancreatitis groups; induced by 20% ethanol (group 2), 48% ethanol (group 3), 80% ethanol (group 4), chronic pancreatitis groups; induced by 20% ethanol (group 5), 48% ethanol (group 6) and by 80% ethanol (group 7). Acute pancreatitis groups were sacrified on postoperative day 3, while the control group and chronic pancreatitis groups were killed on postoperative day 7. Histopathologic evaluation was done, and P acute pancreatitis (100%). Inflammatory infiltration of neutrophils and mononuclear cells, interstitial edema, and focal necrotic areas were seen in the pancreatic tissues. Similarly, all rats in group 6 developed chronic pancreatitis (100%). Interstitial fibrosis, lymphotic infiltration, ductal dilatation, acinar cell atrophy, periductal hyperplasia were seen in the pancreatic tissues. Mortality was seen only in group 7. The biliopancreatic ductal injection of 48% ethanol induced acute and chronic pancreatitis has 100% success rate.

  16. Effect of Chronic Uremia on the Cell Surface Expression of B7 Family Costimulatory Molecules in an HLA-A2 Transgenic Mouse Model of Chronic Kidney Disease.

    Science.gov (United States)

    Makidon, Paul E; Smith, Douglas M; Groom Ii, Jeffery V; Cao, Zhengyi; Landers, Jeffery J; Baker, James R

    2015-08-01

    Uremia due to chronic kidney disease (CKD) in humans is associated with immune dysfunction, increased susceptibility to infections, immune-activation-associated inflammation, and poor responses to vaccines. The pathophysiologic basis of these immune defects is hypothesized to be associated with a wide range of immunologic abnormalities, including an inability to sufficiently express the B7 family (B7-1, CD80; B7-2, CD86) of T-cell costimulatory molecules. However, testing the hypothesis that a state of chronic uremia contributes to attenuated expression of CD80 or CD86 has been difficult because few animal models faithfully recapitulate the immune defects observed in human CKD patients. We used a humanized mouse in a model of surgically induced renal failure and secondary chronic uremia to evaluate the effect of uremia on the expression of these markers. In a manner that resembles the changes observed in CKD patients, surgically induced CKD in mice resulted in decreased costimulatory CD86 expression compared with that in sham-operated controls. Immunodeficiency was functionally demonstrated in this mouse model by documenting an attenuated immune response to a cholera-toxin-based hepatitis B vaccine. This model will be useful for investigating the mechanisms involved in chronic uremia-associated immunodeficiency, poor response to vaccination, and problems associated with immunization of CKD patients.

  17. The Control of Drug Release and Vascular Endothelialization after Hyaluronic Acid-Coated Paclitaxel Multi-Layer Coating Stent Implantation in Porcine Coronary Restenosis Model

    Science.gov (United States)

    Bae, In-Ho; Jeong, Myung Ho; Park, Yong Hwan; Lim, Kyung Seob; Park, Dae Sung; Shim, Jae Won; Kim, Jung Ha; Ahn, Youngkeun; Hong, Young Joon; Sim, Doo Sun

    2017-01-01

    Background and Objectives Hyaluronic acid (HA) is highly biocompatible with cells and the extracellular matrix. In contrast to degradation products of a synthetic polymer, degradation products of HA do not acidify the local environment. The aim of this study was to fabricate an HA-coated paclitaxel (PTX)-eluting stent via simple ionic interactions and to evaluate its effects in vitro and in vivo. Materials and Methods HA and catechol were conjugated by means of an activation agent, and then the stent was immersed in this solution (resulting in a HA-coated stent). After that, PTX was immobilized on the HA-coated stent (resulting in a hyaluronic acid-coated paclitaxel-eluting stent [H-PTX stent]). Study groups were divided into 4 groups: bare metal stent (BMS), HA, H-PTX, and poly (L-lactide)-coated paclitaxel-eluting stent (P-PTX). Stents were randomly implanted in a porcine coronary artery. After 4 weeks, vessels surrounding the stents were isolated and subjected to various analyses. Results Smoothness of the surface was maintained after expansion of the stent. In contrast to a previous study on a PTX-eluting stent, in this study, the PTX was effectively released up to 14 days (a half amount of PTX in 4 days). The proliferation of smooth muscle cells was successfully inhibited (by 80.5±12.11% at 7 days of culture as compared to the control) by PTX released from the stent. Animal experiments showed that the H-PTX stent does not induce an obvious inflammatory response. Nevertheless, restenosis was clearly decreased in the H-PTX stent group (9.8±3.25%) compared to the bare-metal stent group (29.7±8.11%). Conclusion A stent was stably coated with PTX via simple ionic interactions with HA. Restenosis was decreased in the H-PTX group. These results suggest that HA, a natural polymer, is suitable for fabrication of drug-eluting stents (without inflammation) as an alternative to a synthetic polymer.

  18. Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

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    Lee, Hye Won; Ahn, Sang Hoon

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B (CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-naïve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM (Individual Prediction Model), CU-HCC (Chinese University-HCC), GAG-HCC (Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC (Nomogram-HCC), REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM (Liver Stiffness Measurement)-based model, LSM-HCC, and mREACH-B (modified REACH-B). PMID:27729738

  19. Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy

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    Mendonça, Fabricio N.; Santos, Luiz E. C.; Rodrigues, Antônio M.; Gomes da Silva, Sérgio; Arida, Ricardo M.; da Silveira, Gilcélio A.; Scorza, Fulvio A.; Almeida, Antônio-Carlos G.

    2017-01-01

    Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction. PMID:28298884

  20. Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia.

    Science.gov (United States)

    Flores, Gonzalo; Flores-Gómez, Gabriel D; de Jesús Gomez-Villalobos, Ma

    2016-05-01

    Vascular dementia is a devastating disorder not only for the patient, but also for the family because this neurocognitive disorder breaks the patient's independence, and leads to family care of the patient with a high cost for the family. This complex disorder alters memory, learning, judgment, emotional control and social behavior and affects 4% of the elderly world population. The high blood pressure or arterial hypertension is a major risk factor for cerebrovascular disease, which in most cases leads to vascular dementia. Interestingly, this neurocognitive disorder starts after long lasting hypertension, which is associated with reduced cerebral blood flow or hypoperfusion, and complete or incomplete ischemia with cortical thickness. Animal models have been generated to elucidate the pathophysiology of this disorder. It is known that dendritic complexity determines the receptive synaptic contacts, and the loss of dendritic spine and arbor stability are strongly associated with dementia in humans. This review evaluates relevant data of human and animal models that have investigated the link between long-lasting arterial hypertension and neural morphological changes in the context of vascular dementia. We examined the effect of chronic arterial hypertension and aged in vascular dementia. Neural dendritic morphology in the prefrontal cortex and the dorsal hippocampus and nucleus accumbens after chronic hypertension was diskussed in the animal models of hypertension. Chronic hypertension reduced the dendritic length and spine density in aged rats.

  1. A microsimulation model for the development and progression of chronic obstructive pulmonary disease.

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    Tan, Emma; Boessen, Ruud; Fishwick, David; Klein Entink, Rinke; Meijster, Tim; Pronk, Anjoeka; van Duuren-Stuurman, Birgit; Warren, Nick

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is a chronic lung disease that is thought to affect over one million people in Great Britain. The main factor contributing to the development of COPD is tobacco smoke. This paper presents a microsimulation model for the development of COPD, incorporating population dynamics and trends in smoking. The model simulates a population longitudinally throughout their lifetimes, providing projections of future COPD prevalence and evaluation of the effects of changes in risk factor prevalence such as smoking. Sensitivity analysis provides information on the most influential model parameters. The model-predicted prevalence of COPD in 2040 was 17% in males over the age of 35 years (13% amongst non-smokers and 22% amongst smokers), and a modest decline over the next 25 years due to recent trends in smoking rates. The simulation model provides us with valuable information on current and future trends in COPD in Great Britain. It was developed primarily to enable easy extension to evaluate the effects of occupational and environmental exposures on lung function and the prevalence of COPD and to allow evaluation of interventions, such as introducing health surveillance or policy changes. As longitudinal studies for investigating COPD are difficult due to the lengthy follow-up time required and the potentially large number of drop-outs, we anticipate that the model will provide a valuable tool for health impact assessment. An extended model for occupational exposures is under development and will be presented in a subsequent paper.

  2. An animal model of schizophrenia based on chronic LSD administration: old idea, new results.

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    Marona-Lewicka, Danuta; Nichols, Charles D; Nichols, David E

    2011-09-01

    Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as "clearly a paranoid state." We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT(2A) receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP.

  3. Local NMDA receptor blockade attenuates chronic tinnitus and associated brain activity in an animal model.

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    Thomas J Brozoski

    Full Text Available Chronic tinnitus has no broadly effective treatment. Identification of specific markers for tinnitus should facilitate the development of effective therapeutics. Recently it was shown that glutamatergic blockade in the cerebellar paraflocculus, using an antagonist cocktail was successful in reducing chronic tinnitus. The present experiment examined the effect of selective N-methyl d-aspartate (NMDA receptor blockade on tinnitus and associated spontaneous brain activity in a rat model. The NMDA antagonist, D(--2-amino-5-phosphonopentanoic acid (D-AP5 (0.5 mM, was continuously infused for 2 weeks directly to the ipsilateral paraflocculus of rats with tinnitus induced months prior by unilateral noise exposure. Treated rats were compared to untreated normal controls without tinnitus, and to untreated positive controls with tinnitus. D-AP5 significantly decreased tinnitus within three days of beginning treatment, and continued to significantly reduce tinnitus throughout the course of treatment and for 23 days thereafter, at which time testing was halted. At the conclusion of psychophysical testing, neural activity was assessed using manganese enhanced magnetic resonance imaging (MEMRI. In agreement with previous research, untreated animals with chronic tinnitus showed significantly elevated bilateral activity in their paraflocculus and brainstem cochlear nuclei, but not in mid or forebrain structures. In contrast, D-AP5-treated-tinnitus animals showed significantly less bilateral parafloccular and dorsal cochlear nucleus activity, as well as significantly less contralateral ventral cochlear nucleus activity. It was concluded that NMDA-mediated glutamatergic transmission in the paraflocculus appears to be a necessary component of chronic noise-induced tinnitus in a rat model. Additionally, it was confirmed that in this model, elevated spontaneous activity in the cerebellar paraflocculus and auditory brainstem is associated with tinnitus.

  4. Application of transtheoretical model to assess the compliance of chronic periodontitis patients to periodontal therapy

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    Shilpa Emani

    2016-01-01

    Full Text Available Background: The present cross-sectional survey study was conducted to assess whether the transtheoretical model for oral hygiene behavior was interrelated in theoretically consistent directions in chronic periodontitis patients and its applicability to assess the compliance of the chronic periodontitis patients to the treatment suggested. Materials and Methods: A total of 150 chronic periodontitis patients were selected for the proposed study. The selected patients were given four questionnaires that were constructed based on transtheoretical model (TTM, and the patients were divided subsequently into five different groups (precontemplation, contemplation, preparation, action, and maintenance groups based on their answers to the questionnaires. Then, each patient was given four appointments for their periodontal treatment spaced with a time gap of 10 days. The patients visit for each appointments scheduled to them was documented. The results obtained were assessed using TTM. Results: Higher mean pro scores of decisional balance, self-efficacy, and process of change scores was recorded in maintenance group followed by action group, preparation group, contemplation group, and precontemplation group, respectively, whereas higher mean cons score was recorded in precontemplation group followed by contemplation group, preparation group, action group, and maintenance group, respectively. The difference scores of TTM constructs were statistically highly significant between all the five groups. Furthermore, the number of appointment attended in were significantly more than maintenance group followed by action group, preparation group, contemplation group, and precontemplation group. Conclusion: Within the limitations of this study, it can be concluded that transtheoretical model can be successfully applied to chronic periodontitis patients to assess their compliance to the suggested periodontal treatment.

  5. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

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    Cuzzocrea Salvatore

    2011-01-01

    Full Text Available Abstract Background Extracts of Hypericum perforatum (St. John's wort have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF, Novelty-Suppressed Feeding (NSF, Forced Swim Test (FST were performed. Cell proliferation in hippocampal dentate gyrus (DG was investigated by both 5-bromo-2'-deoxyuridine (BrdU and doublecortin (DCX immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

  6. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment.

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    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders; Sandi, Carmen

    2010-10-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core symptom of depression, was assessed by measuring consumption of a palatable solution. Exposure to CUS reduced intake of a palatable solution and this effect was prevented by chronic antidepressant treatment. Moreover, chronic antidepressant treatment decreased depressive-like behavior in a modified forced swim test in stressed rats. Present evidence suggests a role for brain-derived neurotrophic factor (BDNF) in depression. BDNF mRNA levels in the ventral and dorsal hippocampus were assessed by in situ hybridization. Exposure to CUS was not correlated with a decrease but rather with an increase in BDNF mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity.

  7. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

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    Elke S. Reichwaldt

    2016-08-01

    Full Text Available Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.

  8. Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia.

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    Wright, Eric A; d'Esterre, Christopher D; Morrison, Laura B; Cockburn, Neil; Kovacs, Michael; Lee, Ting-Yim

    2016-01-01

    CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155-180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion.

  9. Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia.

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    Eric A Wright

    Full Text Available CT Perfusion (CTP derived cerebral blood flow (CBF thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1 was injected into the brain of Duroc-Cross pigs (n = 11 through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155-180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion.

  10. Modeling chronic dietary cadmium bioaccumulation and toxicity from periphyton to Hyalella azteca.

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    Golding, Lisa A; Borgmann, Uwe; Dixon, D George

    2011-07-01

    A chronic (28-d) Cd saturation bioaccumulation model was developed to quantify the Cd contribution from a natural periphyton diet to Cd in the freshwater amphipod Hyalella azteca. Bioaccumulation was then linked to chronic toxic effects. Juvenile H. azteca were exposed to treatments of Cd in water (3.13-100 nmol/L nominal) and food (389-26,300 nmol/g ash-free dry mass). Cadmium bioaccumulation, survival, and growth were recorded. Dietary Cd was estimated to contribute 21 to 31, 59 to 94, and 40 to 55% to bioaccumulated Cd in H. azteca exposed to treatments of Cd primarily in water, food, and food + water, respectively. Survival as a function of Cd lethal body concentration (679 nmol/g; 95% confidence limits, 617-747) was the most robust endpoint. Body concentration integrated all exposure routes. Based on the lethal body concentration, dietary Cd was predicted to contribute markedly (26-90%) to Cd in H. azteca. Cadmium concentration and food nutritional quality (biomass, chlorophyll a, total lipid, fatty acids, total protein) had no effect on H. azteca nutritional quality (total lipid, fatty acids, total protein) but did influence H. azteca dry weight. This research highlighted the importance of including a dietary component when modeling chronic effects of Cd and when refining endpoints for use in ecological risk assessment and water quality guidelines.

  11. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity.

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    Deshpande, Laxmikant S; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J

    2014-09-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment.

  12. Aligning health information technologies with effective service delivery models to improve chronic disease care

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    Bauer, Amy M.; Thielke, Stephen M.; Katon, Wayne; Unützer, Jürgen; Areán, Patricia

    2014-01-01

    Objective Healthcare reforms in the United States, including the Affordable Care and HITECH Acts, and the NCQA criteria for the Patient Centered Medical Home have promoted health information technology (HIT) and the integration of general medical and mental health services. These developments, which aim to improve chronic disease care have largely occurred in parallel, with little attention to the need for coordination. In this article, the fundamental connections between HIT and improvements in chronic disease management are explored. We use the evidence-based collaborative care model as an example, with attention to health literacy improvement for supporting patient engagement in care. Method A review of the literature was conducted to identify how HIT and collaborative care, an evidence-based model of chronic disease care, support each other. Results Five key principles of effective collaborative care are outlined: care is patient-centered, evidence-based, measurement-based, population-based, and accountable. The potential role of HIT in implementing each principle is discussed. Key features of the mobile health paradigm are described, including how they can extend evidence-based treatment beyond traditional clinical settings. Conclusion HIT, and particularly mobile health, can enhance collaborative care interventions, and thus improve the health of individuals and populations when deployed in integrated delivery systems. PMID:24963895

  13. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

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    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  14. Attachment in medical care: A review of the interpersonal model in chronic disease management.

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    Jimenez, Xavier F

    2017-03-01

    Objective Patient-physician interaction is continually examined in an era prioritizing patient-centered approaches, yet elaboration beyond aspects of communication and empathy is lacking. Major chronic conditions would benefit tremendously from understanding interpersonal aspects of patient-physician encounters. This review intends to provide a concise introduction to the interpersonal model of attachment theory and how it informs both the patient-physician interaction and medical outcomes in chronic care. Methods A narrative review of the theoretical, neurobiological, epidemiological, investigational, and clinical literature on attachment theory and its impact on medical outcomes was conducted, utilizing a variety of key words as searched on PubMed database. Studies and reviews included were of a variety of sources, including textbooks and peer-reviewed journals. Reports in languages other than English were excluded. Results Measurable, discrete attachment styles and behavioral patterns correlate with poor medical outcomes, including nonadherence in insecure dismissing attachment and care overutilization in insecure preoccupied attachment. Furthermore, insecure dismissing attachment is associated with significant mortality. These variables can be easily assessed, and their effects are reversible, as evidenced by collaborative care outcome data. Discussion Attachment theory is useful a model with application in clinical and investigational aspects of chronic illness care. Implications and guidelines are explored.

  15. Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of Alzheimer's Disease.

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    Kruyer, Anna; Soplop, Nadine; Strickland, Sidney; Norris, Erin H

    2015-07-01

    Numerous epidemiological studies link vascular disorders, such as hypertension, diabetes mellitus, and stroke, with Alzheimer's disease (AD). Hypertension, specifically, is an important modifiable risk factor for late-onset AD. To examine the link between midlife hypertension and the onset of AD later in life, we chemically induced chronic hypertension in the TgSwDI mouse model of AD in early adulthood. Hypertension accelerated cognitive deficits in the Barnes maze test (Phypertension induced hippocampal neurodegeneration at an early age in this mouse line (43% reduction in the dorsal subiculum; P<0.05), establishing this as a useful research model of AD with mixed vascular and amyloid pathologies.

  16. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

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    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  17. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

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    Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

    2016-01-01

    We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.

  18. [The medical perspective towards chronic pain: biomedical model and clinical practice].

    Science.gov (United States)

    Lima, Mônica Angelim Gomes de; Trad, Leny A Bomfim

    2007-11-01

    This study aimed to shed light on the meanings ascribed to chronic pain in medical discourse and clinical practice in two Pain Clinics located in University hospitals in Salvador (Bahia) and São Paulo, Brazil. An ethnographic approach used participant observation and semi-structuralized interviews with attending and managing physicians. Data analysis drew on the clinical models developed by Byron Good and the medical rationalities project formulated by Madel Luz. The meanings emerging from the study were the recognition of chronic pain by biomedicine as a disease rather than a symptom, its invisibility to physicians, and its non-communicability and inevitability. The informants suggested the need for valorization of the human encounter in the clinic, exercise of understanding as opposed to suspicion, and negotiation of sustainable therapeutic projects.

  19. Molecular evolution of the porcine type I interferon family: subtype-specific expression and antiviral activity.

    Directory of Open Access Journals (Sweden)

    Yongming Sang

    Full Text Available Type I interferons (IFNs, key antiviral cytokines, evolve to adapt with ever-changing viral threats during vertebrate speciation. Due to novel pathogenic pressure associated with Suidae speciation and domestication, porcine IFNs evolutionarily engender both molecular and functional diversification, which have not been well addressed in pigs, an important livestock species and animal model for biomedical sciences. Annotation of current swine genome assembly Sscrofa10.2 reveals 57 functional genes and 16 pseudogenes of type I IFNs. Subfamilies of multiple IFNA, IFNW and porcine-specific IFND genes are separated into four clusters with ∼ 60 kb intervals within the IFNB/IFNE bordered region in SSC1, and each cluster contains mingled subtypes of IFNA, IFNW and IFND. Further curation of the 57 functional IFN genes indicates that they include 18 potential artifactual duplicates. We performed phylogenetic construction as well as analyses of gene duplication/conversion and natural selection and showed that porcine type I IFN genes have been undergoing active diversification through both gene duplication and conversion. Extensive analyses of the non-coding sequences proximal to all IFN coding regions identified several genomic repetitive elements significantly associated with different IFN subtypes. Family-wide studies further revealed their molecular diversity with respect to differential expression and restrictive activity on the resurgence of a porcine endogenous retrovirus. Based on predicted 3-D structures of representative animal IFNs and inferred activity, we categorized the general functional propensity underlying the structure-activity relationship. Evidence indicates gene expansion of porcine type I IFNs. Genomic repetitive elements that associated with IFN subtypes may serve as molecular signatures of respective IFN subtypes and genomic mechanisms to mediate IFN gene evolution and expression. In summary, the porcine type I IFN profile has

  20. Tachykinins in the porcine pancreas

    DEFF Research Database (Denmark)

    Schmidt, P T; Tornøe, K; Poulsen, Steen Seier

    2000-01-01

    The localization, release, and effects of substance P and neurokinin A were studied in the porcine pancreas and the localization of substance P immunoreactive nerve fibers was examined by immunohistochemistry. The effects of electrical vagus stimulation and capsaicin infusion on tachykinin release...... nerve fibers were localized to islets of Langerhans, acini, ducts, and blood vessels. Vagus stimulation had no effect on substance P and neurokinin A release, whereas capsaicin infusion stimulated release of both. Substance P and neurokinin A infusion increased release of insulin, glucagon, and exocrine...... secretion, whereas somatostatin secretion was unaffected. The effect of substance P on insulin, glucagon, and exocrine secretion was blocked by the NK-1 receptor antagonist. The effect of electrical stimulation of vagus nerves on insulin and exocrine secretion was not influenced by tachykinin receptor...

  1. Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

    Science.gov (United States)

    Jo, Eu-Ri; Jung, Pil-Mun; Choi, Jong-il; Lee, Ju-Woon

    2012-08-01

    In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 106-107 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 105-106 TCID50/g into porcine skin. The D10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D10 was 3.88±0.3 kGy in porcine skin. The D10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

  2. Ex vivo correlation of the permeability of metoprolol across human and porcine buccal mucosa.

    Science.gov (United States)

    Meng-Lund, Emil; Marxen, Eva; Pedersen, Anne Marie L; Müllertz, Anette; Hyrup, Birgitte; Holm, Rene; Jacobsen, Jette

    2014-07-01

    The pH partition theory proposes a correlation between fraction of unionized drug substance and permeability. The aim of this study was to compare the permeability of metoprolol and mannitol in ex vivo human and porcine buccal mucosa models at varying pH to validate whether the porcine permeability model is predictive for human buccal absorption. Human (n = 9-10) and porcine (n = 6-7) buccal mucosa were mounted in a modified Ussing chamber, and the kinetics of metoprolol and mannitol transport was assessed for a period of 5.5 h with the pH values of donor medium set at 7.4, 8.5, and 9.0. In addition, hematoxylin-eosin and Alcian blue-van Gieson were used as tissue stains to evaluate the histology and the presence of acidic polysaccharides (e.g., mucins), respectively. The permeability of metoprolol was decreased in human buccal mucosa by almost twofold when compared with porcine buccal mucosa with a positive correlation (r(2) = 0.96) between the permeability assessed in porcine and human buccal mucosa. There was no change in the degree of either epithelial swelling or desquamation when treating with the pH 9.0 donor medium for 5.5 h. These data suggest that buccal mucosa from pigs can be used to predict human buccal absorption.

  3. Chronic Neuroinflammation in Alzheimer’s Disease: New Perspectives on Animal Models and Promising Candidate Drugs

    Directory of Open Access Journals (Sweden)

    Christopher Millington

    2014-01-01

    Full Text Available Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer’s disease (AD. However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system, and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6 mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6 in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.

  4. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis: A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    Directory of Open Access Journals (Sweden)

    Wang Qi

    2012-08-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228 weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

  5. Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.

    Science.gov (United States)

    Sun, Na; Sun, Panpan; Lv, Haipeng; Sun, Yaogui; Guo, Jianhua; Wang, Zhirui; Luo, Tiantian; Wang, Shaoyu; Li, Hongquan

    2016-04-15

    The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings.

  6. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of

  7. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Science.gov (United States)

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  8. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  9. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Maurizia Rossana Brunetto; Piero Colombatto; Ferruccio Bonino

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.

  10. 猪急性颅高压损伤模型的病理生理及超微结构改变%Pathophysiological and ultrastructural changes in porcine model of acute intracranial hypertension brain injury

    Institute of Scientific and Technical Information of China (English)

    吴伟; 成惠林; 杭春华; 史继新; 印红霞; 吴晋荣; 黎介寿

    2012-01-01

    目的 观察猪急性颅高压损伤模型的病理生理变化及超微结构改变.方法 选用中型猪5只,采用微量泵注射自体动脉血法建立急性颅高压损伤控制模型,模型制备过程中及制备后2h持续监测颅内压、平均动脉压变化,注血后2h行头部CT扫描,24 h取脑行大体切片,苏木精-伊红染色光镜观察组织学病理改变、超微电镜观察受损神经元的超微结构改变.结果 注血后颅内压、平均动脉压均明显上升,最高分别达(51.2±2.5) mmHg和(152.7±12.8) mmHg,颅内压升至约50 mmHg时,出现呼吸、心率改变;头部CT扫描、大体切片均显示脑内血肿形成;电镜检查显示血肿区神经元肿胀,胞质内细胞器数量减少,线粒体肿胀,嵴排列不整齐,粗面内质网颗粒扩张,血管内皮细胞肿胀,基膜不完整,血管周围可见明显水肿带.结论 采用微量泵注射自体动脉血法可建立稳定、可靠的猪急性颅高压损伤控制模型.%Objective To observe the pathophysiological and ultrastructural changes in the porcine model of acute intracranial hypertension brain injury. Methods Autologous arterial blood was injected into the brain in 5 middle-weighted pigs by micro-pump for establishing the brain injury model due to acute intracranial hypertension. And the change of intracranial pressure (ICP) and mean arterial pressure (MAP) were monitored. CT scanning was performed 2 h after blood injection. After H&E staining, histological changes were observed under light microscope and ultrastructural changes under electron microscope. Results ICP and MAP significantly increased after the blood injection, and the peak reached 51.2 ± 2.5 mmHg and 152.7 ± 12.8 mmHg respectively. The porcine respiration and heart rate changed when the ICP increased to about 50 mmHg. CT scanning and pathological examination all showed the brain hematoma formed. Electron microscope examination showed that the neuronal swelling in hematoma area

  11. Utility of Modeling End-Stage Liver Disease in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Kianifar

    2014-01-01

    Full Text Available Introduction: Chronic liver diseases consist of wide spectrum disorders that may be complicated by cirrhosis and therefore need to transplantation. The pediatric end-stage liver disease (PELD score and model of end-stage liver disease (MELD score has been used as predictors of mortality chronic liver diseases listed for liver transplantation. The aim of this study is evaluation of relation between PELDMELD score and evidence of cirrhosis in children with choronic liver disease.   Materials and Method: This cross-sectional study conducted on 106 patients of chronic liver disease referred to Ghaem Haspital, Mashhad University of Medical Science, Iran during 24 months period (2010-2013. PELD and MELD score were calculated for all patients. Clincal and patholoogical findings of cirrhosis were recorded.   Results: Mean age of patients was 68/3 ± 41.8 months. Mean PELDMELD score was -1/59± 9/64. There was significant correlation between PELDMELD score and clinical icter, spelenomegaly, evidence of hepatopulminary syndrome, esophageal varices, evidence of cirrhosis in tissue specimences.   Conclusion: PELDMELD score appear to be benefit for detection of cirrhotic children among paients with choronic liver disease.

  12. Modeling the oxygen uptake kinetics during exercise testing of patients with chronic obstructive pulmonary diseases using nonlinear mixed models

    DEFF Research Database (Denmark)

    Baty, Florent; Ritz, Christian; van Gestel, Arnoldus;

    2016-01-01

    regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple [Formula: see text]O2 kinetics in both research and clinical practice so far. METHODS: In the present study, we...... describe functionality of the R package medrc that extends the framework of the commonly used packages drc and nlme and allows fitting nonlinear mixed effects models for automated nonlinear regression modeling. The methodology was applied to a data set including 6MWT [Formula: see text]O2 kinetics from 61...... patients with chronic obstructive pulmonary disease (disease severity stage II to IV). The mixed effects approach was compared to a traditional curve-by-curve approach. RESULTS: A six-parameter nonlinear regression model was jointly fitted to the set of [Formula: see text]O2 kinetics. Significant...

  13. Characterization of the innate immune response to chronic aspiration in a novel rodent model

    Directory of Open Access Journals (Sweden)

    Lin Shu S

    2007-11-01

    Full Text Available Abstract Background Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. Methods Gastric fluid or normal saline was instilled into the left lung of rats (n = 48 weekly for 4, 8, 12, or 16 weeks (n = 6 each group. Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. Results Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. Conclusion This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.

  14. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  15. Development of porcine model of tachycardia-induced cardiomyopathy by rapid atrial pacing%快速心房起搏制作猪心动过速心肌病动物模型研究

    Institute of Scientific and Technical Information of China (English)

    张超群; 王志荣; 顾万华; 李飞; 程明月; 李承宗; 徐唔

    2013-01-01

    Objective To evaluate the feasibility of developing porcine model of tachycardia - induced cardiomyopathy by rapid atrial pacing. Methods Eight healthy piglets underwent continuous right atrial pacing at 400 beats/min for 2 weeks while two healthy piglets served as normal control. Left ventricular end - systolic volume ( LVESV) , left ventricular end - distolic volume (LVEDV) and left ventricular ejection fraction ( LVEF) were measured by echocardiography . The atrial natriuretic peptide (ANP) concentration was detected before and after rapid atrial pacing . The left ventricular sections were analyzed histologically through hematoxylin and eosin ( H - E) staining. Results Compared to baseline , the LVESV , LVEDV and the level of ANP all increased significantly after 2 weeks rapid pacing (P < 0. 05) , while LVEF decreased significantly [ (61. 6±7. 2)% vs (38.5±5. l)%,P<0. 05]. Left ventricular tissues demonstrated ventricular tissue disorder, focal necrosis , muscle dissolution , edema, interstitial collagen connective tissue proliferation and in -flammatory cell infiltration. Conclusion Short term rapid atrial pacing is an convenient and effective method for develo -ping porcine model of tachycardia - induced cardiomyopathy.%目的 探讨通过快速心房起搏构建猪心动过速性心肌病模型的可行性.方法 10只健康小猪经穿刺颈静脉途径植入AAI型起搏器,8只给予400次/min的快速右心房起搏2周,2只不起搏作为对照组,起搏前后应用超声心动图观测收缩、舒张末期左心室容积大小及左心室射血分数(LVEF),并检测血心房钠尿肽(ANP)水平;通过苏木精-伊红染色观察左心室心肌病理改变.结果 快速起搏2周后,猪左心室收缩末期容积(LVESV)和舒张末期容积(LVEDV)均显著增加(P<0.05);血浆中ANP显著增加,苏木精-伊红染色可见心室组织细胞排列紊乱,出现局灶性坏死、肌溶解、水肿、间质胶原结缔组织增生

  16. Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lan-lan; MING Liang; MA Chuan-geng; CHENG Yan; JIANG Qin

    2005-01-01

    Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

  17. Differences in Whole Blood Gene Expression Associated With Infection Time-course and Extent of Fetal Mortality in a Reproductive Model of type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection

    Science.gov (United States)

    Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females causes fetal death and increased piglet mortality, but there is substantial variation in the extent of reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole bl...

  18. Unlimited-Length Proctocolectomy Utilizing Sequential Intussusception and Pull-Through: Novel Clean Endolumenal NOTE-Assisted Technique With Transanal Natural Orifice Specimen Extraction Without Rectal Stump Opening in a Porcine Model.

    Science.gov (United States)

    Kvasha, Anton; Khalifa, Muhammad; Biswas, Seema; Hamoud, Mohamad; Nordkin, Dmitri; Bramnik, Zakhar; Willenz, Udi; Farraj, Moaad; Waksman, Igor

    2016-10-01

    Transanal, hybrid natural orifice translumenal endoscopic surgery (NOTES) and NOTES-assisted natural orifice specimen extraction techniques hold promise as leaders in the field of natural orifice surgery. We report the feasibility of a novel NOTES assisted technique for unlimited length, clean, endolumenal proctocolectomy in a porcine model. This technique is a modification of a transanal intussusception and pull-through procedure recently published by our group. Rectal mobilization was achieved laparoscopically; this was followed by a transanal recto-rectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached laparoscopically to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. To achieve an unlimited-length proctocolectomy, the IPT step was repeated several times prior to bowel resection. This was facilitated by removing the ligature applied in the first step of this procedure. Once sequential IPT established the desired length of bowel to be resected, a second ligature was placed around the rectum approximating the proximal and distal resection margins. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls. The anastomosis was achieved by deploying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. The minimally invasive nature of this evolving technique as well as its aseptic bowel manipulation has the potential to limit the complications associated with abdominal wall incision and surgical site infection.

  19. Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Bødtkjer, Donna Marie Briggs; Kudryavtseva, Olga;

    2014-01-01

    OBJECTIVE: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including......-like response) was reduced in anhedonic rats (p depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed...... endothelium-dependent hyperpolarization-like relaxation despite up-regulation of the NO and COX-2-dependent pathways in rat mesenteric arteries. These changes could affect peripheral resistance and organ perfusion in major depression....

  20. Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD

    Directory of Open Access Journals (Sweden)

    Fischer Axel

    2006-06-01

    Full Text Available Abstract Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm for 3 (short-term or 20–25 (long-term days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion. In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD.

  1. Challenge models to assess new therapies in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van der Merwe R

    2012-09-01

    Full Text Available René van der Merwe,1 Nestor A Molfino2,31Respiratory Clinical Development, MedImmune Ltd, Cambridge, UK; 2Respiratory Clinical Development, MedImmune, LLC, Gaithersburg, MD, USA, 3KaloBios Pharmaceuticals, South San Francisco, CA, USAAbstract: Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.Keywords: chronic obstructive pulmonary disease, challenge models, therapy assessment

  2. Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model.

    Directory of Open Access Journals (Sweden)

    Shuifeng Deng

    Full Text Available Primary open angle glaucoma (POAG is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs. In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi and late or degraded autophagic vacuoles (AVd accumulated in the ganglion cell layer (GCL and in the inner plexiform layer (IPL as determined by transmission electron microscopy (TEM analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1 and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.

  3. MODELING CHRONIC DISEASE PATIENT FLOWS DIVERTED FROM EMERGENCY DEPARTMENTS TO PATIENT-CENTERED MEDICAL HOMES.

    Science.gov (United States)

    Diaz, Rafael; Behr, Joshua; Kumar, Sameer; Britton, Bruce

    Chronic Disease is defined as a long lasting health condition, which can develop and/or worsen over an extended time, but which can also be controlled. The monetary and budgetary toll due to its persistent nature has become unsustainable and requires pressing actions to limit their incidence and burden. This paper demonstrates the utility of the System Dynamics approach to simulate the behavior of key factors involved in the implementation of chronic disease management. We model the patient flow diversion from emergency departments (ED) to patient-centered medical homes (PCMH), with emphasis on the visit rates, as well as the effect of insurance coverage, in an effort to assure continuity of quality care for Asthma patients at lower costs. The model is used as an evaluative method to identify conditions of a maintained health status through adequate policy planning, in terms of resources and capacity. This approach gives decision makers the ability to track the level of implementation of the intervention and generate knowledge about dynamics between population demands and the intervention effectiveness. The functionality of the model is demonstrated through the consideration of hypothetical scenarios executed using sensitivity analysis.

  4. International care models for chronic kidney disease: methods and economics--United States.

    Science.gov (United States)

    Crooks, Peter

    2004-01-01

    In the United States, there is a major chronic kidney disease (CKD) problem with over 8 million adults having stage 3 or 4 CKD. There is good medical evidence that many of these patients can benefit from focused interventions. And while there are strong theoretical reasons to believe these interventions are cost-effective, there are little published data to back up this assertion. However, despite the lack of financial data proving cost-effectiveness and against the background of a disorganized health care system in the US, some models of CKD care are being employed. At the present time, the most comprehensive models of care in the US are emerging in vertically integrated health care programs. Other models of care are developing in the setting of managed care health plans that employ CKD disease management programs, either developed internally or in partnership with renal disease management companies.

  5. Space-time Bayesian survival modeling of chronic wasting disease in deer.

    Science.gov (United States)

    Song, Hae-Ryoung; Lawson, Andrew

    2009-09-01

    The primary objectives of this study are to describe the spatial and temporal variation in disease prevalence of chronic wasting disease (CWD), to assess the effect of demographic factors such as age and sex on disease prevalence and to model the disease clustering effects over space and time. We propose a Bayesian hierarchical survival model where latent parameters capture temporal and spatial trends in disease incidence, incorporating several individual covariates and random effects. The model is applied to a data set which consists of 65085 harvested deer in Wisconsin from 2002 to 2006. We found significant sex effects, spatial effects, temporal effects and spatio-temporal interacted effects in CWD infection in deer in Wisconsin. The risk of infection for male deer was significantly higher than that of female deer, and CWD has been significantly different over space, time, and space and time based on the harvest samples.

  6. Effects of Exercise on Behavior and Peripheral Blood Lymphocyte Apoptosis in a Rat Model of Chronic Fatigue Syndrome

    Institute of Scientific and Technical Information of China (English)

    邹军; 苑建齐; 吕爽; 屠嘉衡

    2010-01-01

    This study examined the effects of exercise on behavior and peripheral blood leukocyte apoptosis in a rat model of chronic fatigue syndrome(CFS).Thirty-six healthy male Sprague-Dawley rats were equally randomized into 3 groups:the control group,CFS model group and the exercise group in terms of body weight.A total of 25 rats entered the final statistical analysis due to 11 deaths during the study.CFS model was established by subjecting the rats in CFS model group and exercise group to electric shock,chronic...

  7. The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

    Science.gov (United States)

    Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

    2016-05-01

    The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe.

  8. Laparoscopic abdominal wall components separation in a porcine model of intra-abdominai hypertension%腹腔镜腹壁结构分离治疗腹腔内高压的动物实验

    Institute of Scientific and Technical Information of China (English)

    李世宽; 胡三元

    2009-01-01

    目的 通过动物实验,研究腹腔镜腹壁结构分离技术治疗腹腔内高压的效果.方法 8头巴马香猪于全麻下手术,通过腹腔灌注CO2建立腹腔高压(IAH)模型.于腹肌平面上方建立皮下隧道,在腹腔镜的监测下以超声刀切开腹外斜肌腱膜的止点,记录术前、单侧减压和双侧减压后的腹腔内压(IAP)、腰围(WL)、中心静脉压(CVP)、平均动脉压(MAP)和心率(HR)的变化.结果 建立IAH(25 mm Hg)后,WL为(65.3±2.5)cm,MAP为(88±14)mm Hg,HR为(115±9)次/min,CVP为(10.8±2.2)cm H2O.实施腹腔镜腹壁结构分离后,IAP降至(16.0±1.5)mm Hg(P<0.01),WL升至(83.1±1.9)cm(P<0.01),MAP升至(100±12)mm Hg(P<0.01),HR降至(97±7)次/min(P<0.01),CVP降至(7.3±1.8)cmH2O(P<0.01).结论 IAP的变化可引起巴马香猪的血液动力学改变,腹腔镜腹壁结构分离技术可显著降低其IAH,从而改善血液动力学.%Objective To determine the effect of laparoscopic abdominal wall components separation procedure on a porcine model of intra-abdominal hypertension (IAH). Methods IAH to 25 nun Hg was created by insufllating carbon dioxide into abdominal cavity of eight anesthetized pigs. Bilateral subcutaneous tunnels above the plane of the abdominal musculature were developed. Dissection of the external oblique insertion and development of the plane between external and internal oblique muscles was performed using ultrasonic scalpel monitored by laparoscopy. Changes in intra-abdominal pressure (IAP), waistline (WL), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP) were recorded. Results Following intra-abdominal hypertension, WL, MAP, HR and CVP changed significantly. After laparoscopic abdominal wall components separation, there was a significant decrease in IAP from 25 mm Hg to ( 16. 0 ± 1.5 ) mm Hg ( P < 0. 01 ). Also, this procedure increased WL by (5.6 ± 2. 0) cm [ from (65.3 ± 2. 5 ) cm to (88 ± 14) cm; P < 0. 01 ]. Due to abdominal depression, the MAP

  9. Exercise training-induced adaptations in mediators of sustained endothelium-dependent coronary artery relaxation in a porcine model of ischemic heart disease

    Science.gov (United States)

    Heaps, Cristine L.; Robles, Juan Carlos; Sarin, Vandana; Mattox, Mildred L.; Parker, Janet L.

    2014-01-01

    Objective Test the hypothesis that exercise training enhances sustained relaxation to persistent endothelium-dependent vasodilator exposure via increased nitric oxide contribution in small coronary arteries of control and ischemic hearts. Methods Yucatan swine were designated to a control group or a group in which an ameroid constrictor was placed around the proximal LCX. Subsequently, pigs from both groups were assigned to exercise (5 days/week; 16 weeks) or sedentary regimens. Coronary arteries (~100–350 μm) were isolated from control pigs and from both nonoccluded and collateral-dependent regions of chronically-occluded hearts. Results In arteries from control pigs, training significantly enhanced relaxation responses to increasing concentrations of bradykinin (10−10 to 10−7 M) and sustained relaxation to a single bradykinin concentration (30 nM), which were abolished by NOS inhibition. Training also significantly prolonged bradykinin-mediated relaxation in collateral-dependent arteries of occluded pigs, which was associated with more persistent increases in endothelial cellular Ca2+ levels, and reversed with NOS inhibition. Protein levels for eNOS and p-eNOS-(Ser1179), but not caveolin-1, Hsp90, or Akt, were significantly increased with occlusion, independent of training state. Conclusions Exercise training enhances sustained relaxation to endothelium-dependent agonist stimulation in small arteries of control and ischemic hearts by enhanced nitric oxide contribution and endothelial Ca2+ responses. PMID:24447072

  10. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

    Directory of Open Access Journals (Sweden)

    Massimo Collino

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  11. Path analysis of the chronicity of depression using the comprehensive developmental model framework.

    Science.gov (United States)

    Fandiño-Losada, Andrés; Bangdiwala, Shrikant I; Lavebratt, Catharina; Forsell, Yvonne

    2016-07-01

    Background Depressive disorder is recognized as recurrent or chronic in the majority of affected individuals; but literature is not consistent about determinants of the disorder course. Aims To analyse the relationships between familial, personal and environmental characteristics in different life phases and their effects on the chronicity of depression in a population-based sample. Methods It was a longitudinal panel study with three waves (W1-W3) for 651 adult men and women with diagnosis of minor/major depression or dysthymia at W1 of the Swedish PART (mental health, work and relations) study. Risk factors and co-morbidities were assessed with questionnaires. The main outcome was an episode of minor/major depression or dysthymia at 10-12 years of follow-up (W3). Liability for depressive episodes was determined using exploratory structural equation modelling (SEM), following a path approach with step-wise specification searches. Results Most of the risk factors determined, directly or indirectly, depression severity at W3. Somatic trait anxiety, partner loss and other negative life events at W1, depressive symptoms at W2, and life difficulties and other dependent life events at W3 had direct effects on the outcome. Conclusions SEM model revealed complex and intertwined psychopathological pathways leading to chronicity of depression, given previous episodes, which could be assembled in two main mechanisms: a depressive-internalizing path and an adversity path comprised of life events. Pathways are simpler than those of depression occurrence, emphasizing the relevance of personality factors as depression determinants, and excluding disability levels, co-morbidities and social support. These novel findings need to be replicated in future studies.

  12. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model

    OpenAIRE

    Pilat, Nina; Farkas, Andreas M.; Mahr, Benedikt; Schwarz, Christoph; Unger, Lukas; Hock, Karin; Oberhuber, Rupert; Aumayr, Klaus; Wrba, Fritz; Wekerle, Thomas

    2014-01-01

    Background The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection. Metho...

  13. Comparative experimental evaluation of the efficacy of Prostamol Uno and Samprost on rat model of chronic aseptic prostate inflammation.

    Science.gov (United States)

    Pahomova, A V; Borovskaja, T G; Fomina, T I; Ermolaeva, L A; Vychuzhanina, A V; Rumpel, O A; Granstrem, O K; Baranova, O V

    2011-11-01

    Comparative experimental evaluation of the efficiency of prostatotropic drugs Prostamol Uno and Samprost on the model of the chronic aseptic prostate inflammation in rats was performed. It was established that peptide drug Samprost decelerates sclerotic processes in the prostate gland to a greater extent than herbal preparation Prostamol Uno. Both products equally stimulate secretory activity of the gland. Prostamol Uno, unlike Samprost, prevents the development of reduced sexual motivation, one of the complications of chronic prostatitis.

  14. Existence of proviral porcine endogenous retrovirus in fresh and decellularised porcine tissues

    Directory of Open Access Journals (Sweden)

    Prabha S

    2008-01-01

    Full Text Available Purpose: Swine are expected to be utilized as xenograft donors for both whole organ and cellular transplantation. A major concern in using porcine organs for transplantation is the potential of transmission of porcine endogenous retrovirus (PERV. Tissue-engineered or decellularised heart valves have already been implanted in humans and have been marketed by certain companies after Food and Drug Administration (FDA approval. The aim of this study was to examine the existence of porcine endogenous retrovirus (PERV in fresh and decellularised porcine tissues. Methods: Porcine tissues (both fresh and decellularised were analysed using validated assays specific for PERV: polymerase chain reaction (PCR, reverse transcriptase polymerase chain reaction (RT-PCR. Results: PERV specific GAG sequences were found in the porcine heart tissue samples using PCR for DNA and RT- PCR for RNA. All tissue samples (both fresh and treated tissues like aortic valve, pulmonary valve and heart muscle showed the presence of PERV DNA. RT PCR for PERV was positive in all fresh tissues and was found to be negative in decellularised treated tissues. Conclusions: PCR is a rapid, specific test for the detection of PERV virus in xenografts. These findings have demonstrated that the presence of proviral DNA form of PERV in porcine tissues needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.

  15. Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

    Science.gov (United States)

    Pfaff, Johannes; Mathys, Christian; Mausberg, Anne K.; Bendszus, Martin; Pham, Mirko; Hartung, Hans-Peter; Kieseier, Bernd C.

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker. PMID:27711247

  16. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  17. Development of chronic and acute golden Syrian hamster infection models with Leptospira borgpetersenii serovar Hardjo.

    Science.gov (United States)

    Zuerner, R L; Alt, D P; Palmer, M V

    2012-03-01

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several Leptospira species. Onset of an acute lethal infection following inoculation with several pathogenic Leptospira species has been widely adopted for pathogenesis studies. An important exception is the outcome following inoculation of hamsters with live L. borgpetersenii serovar Hardjo, the primary cause of bovine leptospirosis and a cause of human infections. Typically, inoculation of hamsters with L. borgpetersenii serovar Hardjo fails to induce clinical signs of infection. In this study, the authors defined LD(50) and ID(50) for 2 strains of L. borgpetersenii serovar Hardjo: JB197 and 203. Both strains infected hamsters with ID(50) values of approximately 1.5 × 10(2) bacteria yet differed in tissue invasion and interaction with leukocytes, resulting in widely divergent clinical outcomes. Hamsters infected with strain 203 established renal colonization within 4 days postinfection and remained asymptomatic with chronic renal infections similar to cattle infected with serovar Hardjo. In contrast, hamsters infected with strain JB197 developed a rapidly debilitating disease typical of acute leptospirosis common in accidental hosts (eg, humans) with an LD(50) of 3.6 × 10(4) bacteria. Evidence that strain JB197 resides in both extracellular and intracellular environments during hamster infection was obtained. Development of models that result in chronic and acute forms of leptospirosis provides a platform to study L. borgpetersenii pathogenesis and to test vaccines for the prevention of leptospirosis.

  18. Which clip? A prospective comparative study of retention rates of endoscopic clips on normal mucosa and ulcers in a porcine model

    Directory of Open Access Journals (Sweden)

    Payal Saxena

    2014-01-01

    Full Text Available Background/Aim: There are currently no data on the relative retention rates of the Instinct clip, Resolution clip, and QuickClip2Long. Also, it is unknown whether retention rate differs when clips are applied to ulcerated rather than normal mucosa. The aim of this study is to compare the retention rates of three commonly used endoscopic clips. Materials and Methods: Six pigs underwent upper endoscopy with placement of one of each of the three types of clips on normal mucosa in the gastric body. Three mucosal resections were also performed to create "ulcers." Each ulcer was closed with placement of one of the three different clips. Repeat endoscopy was performed weekly for up to 4 weeks. Results: Only the Instinct and Resolution clips remained attached for the duration of the study (4 weeks. At each time point, a greater proportion of Instinct clips were retained on normal mucosa, followed by Resolution clips. QuickClip2Long had the lowest retention rate on normal mucosa. Similar retention rates of Instinct clips and Resolution clips were seen on simulated ulcers, although both were superior to QuickClip2Long. However, the difference did not reach statistical significance. All QuickClip2Long clips were dislodged at 4 weeks in both the groups. Conclusions: The Resolution and Instinct clips have comparable retention rates and both appeared to be better than the QuickClip2Long on normal mucosa-simulated ulcers; however this did not reach statistical significance. Both the Resolution clip and the Instinct clip may be preferred in clinical situations when long-term clip attachment is required, including marking of tumors for radiotherapy and anchoring feeding tubes or stents. Either of the currently available clips may be suitable for closure of iatrogenic mucosal defects without features of chronicity.

  19. The effect of subretinal viscoelastics on the porcine retinal function

    DEFF Research Database (Denmark)

    Sørensen, Nina Fischer; Ejstrup, Rasmus; Svahn, Thøger Frøsig

    2012-01-01

    The functional consequence of long-term retinal detachment in the porcine model is examined by multifocal electroretinography (mfERG). Retinal detachment (RD) in humans leaves permanent visual impairment, despite anatomical successful reattachment surgery. To improve treatment, adjuvant...... for the 6 weeks of follow-up. The P1 amplitude of the mfERG did not differ significantly between the detached areas, the surrounding attached areas, and the healthy eye (p¿=¿0.25). Similarly, P1 implicit time did not differ between the areas (p¿=¿0.85). The lack of functional consequences of long-term RD...

  20. Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Liu; Jian-Lin Wu; Jian Liang; Tao Zhang,; Qing-Shou Sheng

    2012-01-01

    AIM:To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.METHODS:We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals.Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis.A new fibrosis index [globulin/platelet (GP) model] was developed,including globulin (GLOB) and platelet count (PLT).GP model =GLOB (g/mL) x 100/PLT (x 109/L).We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.RESULTS:Thirteen clinical biochemical and hematological variables [sex,age,PLT,alanine aminotransferase,aspartate aminotransferase (AST),albumin,GLOB,total bilirubin (T.bil),direct bilirubin (D.bil),glutamyl transferase,alkaline phosphatase,HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1,F2-F3 and F4).Bivariate Spearman's rank correlation analysis showed that six variables,including age,PLT,T.bil,D.bil,GLOB and PT,were correlated with the three fibrosis stages (FS).Correlation coefficients were 0.23,-0.412,0.208,0.220,0.314 and 0.212; and P value was 0.014,< 0.001,0.026,0.018,0.001 and 0.024,respectively.Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT:F =11.772,P <0.001; GLOB:F =6.612,P =0.002).Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R2 =0.237).By Spearman's rank correlation analysis,GP model was significantly correlated with the three FS (r =0.466,P < 0.001).The median values in F0-F1,F2-F3 and F4 were 1.461,1.720 and 2.634.Compared with the six available models (fibrosis index,AST-platelet ratio,FIB-4,fibrosis-cirrhosis index and age-AST model and age-PLT ratio),GP model showed a highest correlation

  1. Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation

    Directory of Open Access Journals (Sweden)

    Mok Joanie

    2010-09-01

    Full Text Available Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant chronic systems. Methods To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days or chronic (12 weeks cigarette smoke exposure (CSE using female, C57BL/6 mice (n = 7-10. To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d., roflumilast (3 mg kg-1; p.o., q.d. and fluvastatin (2 mg kg-1; p.o., b.i.d. were dosed 1 h before (and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start, we confirmed that the inflammatory phenotypes were different after acute (3 days versus chronic (12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs, macrophage and lymphocyte numbers were all increased (p Conclusions These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

  2. Molecular cloning of a cDNA encoding the porcine type XVII collagen noncollagenous 16 A domain and localization of the domain to the upper part of porcine skin basement membrane zone.

    Science.gov (United States)

    Xu, Luting; Olivry, Thierry; Chan, Lawrence S

    2004-06-01

    Bullous pemphigoid is an autoimmune blistering human skin disease mediated by immunoglobulin (Ig)G autoantibodies targeting skin basement membrane component type XVII collagen, a transmembrane protein. Also designated BP180 and BPAG2, type XVII collagen is an extracellular matrix element essential for the connection between the epidermis and the underlying dermis. In addition to being a target antigen in the human disease bullous pemphigoid, type XVII collagen is also targeted by autoantibodies of canine, feline, equine and porcine patients suffering from a similar blistering skin disease. Previously, enzyme-linked immunosorbent assay and Western blot analyses have shown that autoantibodies from pigs affected with bullous pemphigoid recognize the human NC16A domain of type XVII collagen. To facilitate the development of porcine model of bullous pemphigoid, we isolated cDNA encoding the porcine type XVII collagen NC16A domain using a reverse transcription-polymerase chain reaction technique. The amino acids deduced from the NC16A cDNA showed 61% identity with the sequence of human NC16A. An antibody generated against a 20-amino acid peptide within the porcine NC16A localized the NC16A epitope to the upper part of porcine skin basement membrane zone. Our data provide further information of the porcine bullous pemphigoid target antigen and may help investigators for their further studies of this disease.

  3. A two-phase model for chronic disease processes under intermittent inspection.

    Science.gov (United States)

    Wu, Ying; Cook, Richard J

    2017-02-26

    A model is developed for chronic diseases with an indolent phase that is followed by a phase with more active disease resulting in progression and damage. The time scales for the intensity functions for the active phase are more naturally based on the time since the start of the active phase, corresponding to a semi-Markov formulation. This two-phase model enables one to fit a separate regression model for the duration of the indolent phase and intensity-based models for the more active second phase. In cohort studies for which the disease status is only known at a series of clinical assessment times, transition times are interval-censored, which means the time origin for phase II is interval-censored. Weakly parametric models with piecewise constant baseline hazard and rate functions are specified, and an expectation-maximization algorithm is described for model fitting. Simulation studies examining the performance of the proposed model show good performance under maximum likelihood and two-stage estimation. An application to data from the motivating study of disease progression in psoriatic arthritis illustrates the procedure and identifies new human leukocyte antigens associated with the duration of the indolent phase. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Prevalence of porcine endogenous retrovirus in Chinese pig breeds and in patients treated with a porcine liver cell-based bioreactor

    Institute of Scientific and Technical Information of China (English)

    Qing Liu; Zheng Liu; Evangelos Dalakas

    2005-01-01

    AIM: To determine the prevalence of porcine endogenous retrovirus (PERV) in various pig breeds raised in China including Chinese experimental mini-pigs by PERV-reverse transcriptase (PERV-RT enzyme). Moreover, the potential for infection of PERV was investigated in patients treated with a bioreactor based on porcine liver cells (n = 3).METHODS: Pig serum, liver and musde cell-free supematants were collected from various Chinese pig breeds. Porcine hepatocytes were isolated with a two-step perfusion method. Three patients with acute or chronic liver failure were treated with a bioartificial liver support system (BALSS) for 8-12 h and serum samples were collected from the patients before, immediately after and 30 d after treatment.RESULTS: The activities of PERV-RT enzyme in pig liver and muscle cell-free supernatants were higher than in normal human controls. PERV-TR enzyme activity did not increase in patients before and after 1 mo of treatment.PERV-RT activities were not significantly different when compared with pre-treatment group (1.544±0.155576), the post-treatment groups (1.501±0.053507, 1.461±0.033808 and 1.6006667±0.01963 for 0, 14 and 30 d post-treatment,respectively, P>0.05), and normal control group (1.440±1.0641, P>0.05). RT enzyme activity in Chinese experimental mini-pigs was higher than in normal human control group (1.440±1.0641 U/mL, P0.05) when compared with the pig breeds except in the muscle supernatants. All the samples including muscle and liver cell supernatants from the Chinese mini-experimental pigs and the four domestic Chinese pig breeds contained PERVs.CONCLUSION: These results suggest that the risk of PERV infection through BALSS containing porcine liver cells without immunosuppressants may be quite low. Although there were PERVs in Chinese experimental mini-pigs and porcine liver cell culture suspensions, we did not find any evidence of persistent PERV infection in patients treated with this porcine hepatocyte-based bioartificial

  5. Rectal stenosis in pigs associated with Salmonella Typhimurium and porcine circovirus type 2 (PCV2 infection

    Directory of Open Access Journals (Sweden)

    Tatiane Terumi Negrão Watanabe

    2011-06-01

    Full Text Available Rectal stricture is an acquired annular fibrous constriction of the rectum that results from a variety of chronic necrotizing enteric diseases. In pigs, it is in most cases a sequel of Salmonella infection. Porcine circovirus type 2 (PCV2 is a known pathogen causing immunosuppression in pigs worldwide. PCV2 infected pigs may be predisposed to salmonellosis. In this report, rectal stenosis was observed in 160 pigs from a herd that experienced an outbreak of enteric salmonellosis over a 4-month period. Distension of the abdominal wall and diarrhea were the main clinical signs observed. Five animals were analyzed showing annular cicatrization of the rectal wall 5.0-7.0 cm anterior to the anorectal junction and Salmonella-positive immunostaining in the large intestine. Salmonella Typhimurium was isolated from fragments of the large intestine. Porcine circovirus type 2 antigen was observed in the mesenteric lymph-node in 4 pigs and in the large intestine in 3 pigs.

  6. DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...... validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian...

  7. Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases.

    Science.gov (United States)

    Lee, Kyung-Ah; Lee, Won-Jae

    2014-01-01

    The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis. In this review, we examine recent exciting observations in Drosophila gut-microbiota interactions, particularly the links among the host immune genotype, the microbial community structure, and the host inflammatory phenotype. Future genetic analyses using Drosophila model system will provide a valuable outcome for understanding the evolutionarily conserved mechanisms that underlie intestinal dysbiosis and chronic inflammatory diseases.

  8. Modelling management of chronic illness in everyday life: A common-sense approach

    Directory of Open Access Journals (Sweden)

    Howard Leventhal

    2016-04-01

    Full Text Available The Commonsense Model of Self-Regulation (CSM has a history of over 50 years as a theoretical framework that explicates the processes by which individuals form cognitive, affective, and behavioral representations of health threats. This article summarizes the major components of individuals' "commonsense models", the underlying assumptions of the CSM as a theory of dynamic behavior change, and the major empirical evidence that have developed these aspects of the CSM since its inception. We also discuss ongoing changes to the theory itself as well as its use in medical practice for optimizing patients' self-management of chronic health threats. The final section focuses on future directions for the theory and its application.

  9. Heat sensitivity of porcine IgG.

    Science.gov (United States)

    Metzger, J J; Bourdieu, C; Rouze, P; Houdayer, M

    1975-09-01

    The sensitivity to heat of porcine IgG was studied. The serum from immunized pigs was heated at 56 degrees C for 30 min as for decomplementation. The elution pattern of the serum proteins on an agarose gel column showed a dramatic change with the appearance of a large peak of the gel-excluded material. This peak contained mainly IgG molecules which still retained its antibody activity. This fact points to misinterpretations which can easily occur in 7S and 19S antibody recognition during the porcine immune response. Correlation is suggested of this property with the large number of interheavy chain disulfide bridges present in porcine IgG.

  10. Gene Expression Profiling in Porcine Fetal Thymus

    Institute of Scientific and Technical Information of China (English)

    Yanjiong Chen; Shengbin Li; Lin Ye; Jianing Geng; Yajun Deng; Songnian Hu

    2003-01-01

    obtain an initial overview of gene diversity and expression pattern in porcinethymus, 11,712 ESTs (Expressed Sequence Tags) from 100-day-old porcine thymus(FTY) were sequenced and 7,071 cleaned ESTs were used for gene expressionanalysis. Clustered by the PHRAP program, 959 contigs and 3,074 singlets wereobtained. Blast search showed that 806 contigs and 1,669 singlets (totally 5,442ESTs) had homologues in GenBank and 1,629 ESTs were novel. According to theGene Ontology classification, 36.99% ESTs were cataloged into the gene expressiongroup, indicating that although the functional gene (18.78% in defense group) ofthymus is expressed in a certain degree, the 100-day-old porcine thymus still existsin a developmental stage. Comparative analysis showed that the gene expressionpattern of the 100-day-old porcine thymus is similar to that of the human infantthymus.

  11. Binding Studies on Isolated Porcine Small Intestinal Mucosa and in vitro Toxicity Studies Reveal Lack of Effect of C. perfringens Beta-Toxin on the Porcine Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Simone Roos

    2015-04-01

    Full Text Available Beta-toxin (CPB is the essential virulence factor of C. perfringens type C causing necrotizing enteritis (NE in different hosts. Using a pig infection model, we showed that CPB targets small intestinal endothelial cells. Its effect on the porcine intestinal epithelium, however, could not be adequately investigated by this approach. Using porcine neonatal jejunal explants and cryosections, we performed in situ binding studies with CPB. We confirmed binding of CPB to endothelial but could not detect binding to epithelial cells. In contrast, the intact epithelial layer inhibited CPB penetration into deeper intestinal layers. CPB failed to induce cytopathic effects in cultured polarized porcine intestinal epithelial cells (IPEC-J2 and primary jejunal epithelial cells. C. perfringens type C culture supernatants were toxic for cell cultures. This, however, was not inhibited by CPB neutralization. Our results show that, in the porcine small intestine, CPB primarily targets endothelial cells and does not bind to epithelial cells. An intact intestinal epithelial layer prevents CPB diffusion into underlying tissue and CPB alone does not cause direct damage to intestinal epithelial cells. Additional factors might be involved in the early epithelial damage which is needed for CPB diffusion towards its endothelial targets in the small intestine.

  12. A partial hearing animal model for chronic electro-acoustic stimulation

    Science.gov (United States)

    Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

    2014-08-01

    Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual

  13. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  14. Nociceptive and Inflammatory Mediator Upregulation in a Mouse Model of Chronic Prostatitis

    Science.gov (United States)

    Schwartz, Erica S.; Xie, Amy; La, Jun-Ho; Gebhart, G.F.

    2015-01-01

    Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis. PMID:25915147

  15. Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models.

    Directory of Open Access Journals (Sweden)

    Mariko Matsui

    Full Text Available Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. Humans can be infected after exposure to contaminated urine of reservoir animals, usually rodents, regarded as typical asymptomatic carriers of leptospires. In contrast, accidental hosts may present an acute form of leptospirosis with a range of clinical symptoms including the development of Acute Kidney Injury (AKI. Chronic Kidney Disease (CKD is considered as a possible AKI-residual sequela but little is known about the renal pathophysiology consequent to leptospirosis infection. Herein, we studied the renal morphological alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the golden Syrian hamster that survived the infection, becoming carrier of virulent leptospires, and the OF1 mouse, a usual reservoir of the bacteria. Animals were monitored until 28 days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infection. Hamsters developed morphological alterations in the kidneys with tubulointerstitial nephritis and fibrosis. Grading of lesions revealed higher scores in hamsters compared to the slight alterations observed in the mouse kidneys, irrespective of the bacterial load. Interestingly, pro-fibrotic TGF-β was downregulated in mouse kidneys. Moreover, cytokines IL-1β and IL-10, and chemokines MIP-1α/CCL3 and IP-10/CXCL-10 were significantly upregulated in hamster kidneys compared to mice. These results suggest a possible maintenance of inflammatory processes in the hamster kidneys with the infiltration of inflammatory cells in response to bacterial carriage, resulting in alterations of renal tissues. In contrast, lower expression levels in mouse kidneys indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms.

  16. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants

    Science.gov (United States)

    Methicillin-resistant Staphylococcus aureus (MRSA) can infect wounds and produce difficult-to- treat biofilms. To determine the extent that MRSA biofilms can deplete oxygen, change pH and damage host tissue, we developed a porcine dermal explant model on which we cultured GFP-labeled MRSA biofilms. ...

  17. Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon;

    is a requirement for activation of CTLs. Previously, the development of therapeutic anti-cancer vaccines have largely been based on rodent models, in particular mice; however the majority of these fail to establish a therapeutic response once put into clinical trials. Pigs have the potential of serving as a model...... superior to rodents as they are more closely related to humans in terms of immunology and physiology. Here, we introduce pigs as a supplementary large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, two tumor...... antigens previously identified as important players in human cancer development and progression, were used as vaccine targets. Using peptide-MHC-I binding predictors we identified IDO-derived and RhoC-derived candidate peptides potentially binding to five different broadly distributed SLA molecules. We...

  18. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... alcohol abuse over many years. Repeated episodes of acute ... chronic pancreatitis. Genetics may be a factor in some cases. ...

  19. The proteasome inhibitor MG132 attenuates skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    马碧蔓

    2013-01-01

    Objective To investigate the effect of the proteasome inhibitor MG-132 on skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease (COPD) and is potential mechanisms.Methods The COPD rat model was established by instillation of LPS and exposure

  20. 以家猪作为超声内镜引导下腹腔神经节穿刺术模型的实验研究%Porcine model for endoscopic ultrasound guided celiac plexus paracentesis

    Institute of Scientific and Technical Information of China (English)

    王凯旋; 金震东; 湛先保; 陈洁; 刘岩; 李兆申

    2010-01-01

    目的 通过在健康家养猪进行超声内镜引导下腹腔神经节穿刺操作训练探讨其可行性和应用价值.方法 选择6只健康家养猪用于研究.术前肌内注射盐酸氯胺酮10 mg/kg镇静,动物安静后给予静脉缓慢注射3%戊巴比妥钠0.8 ml/kg.麻醉稳定后进行穿刺操作并植入空粒子,术后行CT增强扫描以辅助判断穿刺是否成功.结果 试验动物均无死亡,除1只家猪穿刺后CT扫描发现粒子在胃腔内,隔日再行穿刺种植粒子成功,其余均一次性穿刺成功.行CT增强扫描发现粒子定位准确,均匀分布于腹主动脉腹腔干起始部的两侧.结论 家猪的解剖结构与人类相似,可作为初学者进行超声内镜引导下腹腔神经丛穿刺术培训的理想动物模型.%Objective To explore the feasibility of establishing porcine model for training of endoscopic ultrasound (EUS) guided celiac plexus paracentesis.Methods A total of 6 healthy pigs were sedated with an intramuscular injection of Ketamin at 10 mg/kg,followed by intravenous injection of 3% pentobarbital at 0.8 ml/kg.EUS was then performed and empty seeds were implanted into celiac plexus.Enhanced CT scan was performed to confirm the location of the implanted seeds.Results No animal died after the procedure.All seeds were accurately distributed on both sides of the celiac trunk except in one pig the seed was found in stomach by CT scan and was re-implanted another day.Conclusion Pigs are similar to human in anatomic structure and they can be excellent models for beginner endoscopy physicians to acquire the skill of EUS guided celiac plexus paracentesis.

  1. Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel porcine model: studies with cerebral microdialysis with high temporal resolution.

    Directory of Open Access Journals (Sweden)

    Christoffer Nyberg

    Full Text Available BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed. OBJECTIVE: To study early cerebral energy changes in an animal model. METHODS: Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate. RESULTS: In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia. CONCLUSION: The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.

  2. Effects of long- and short-chain fatty acids on the release of gastrointestinal hormones using an ex vivo porcine intestinal tissue model

    NARCIS (Netherlands)

    Voortman, T.; Hendriks, H.F.J.; Witkamp, R.F.; Wortelboer, H.M.

    2012-01-01

    Gastrointestinal (GI) peptide hormones play an important role in short-term regulation of food intake and blood glucose levels. Modulating their release is of potential relevance for weight management and possibly diabetes. As currently available models are hard to extrapolate to the human situation

  3. Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-09-01

    Full Text Available Introduction: To date, isolated cell based blood-brain barrier (BBB models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs isolated from different species vary in terms of bioelectrical and permeability properties. Methods: To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM. The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. Results: The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 W.cm2 than BBCECs (~700 W.cm2 - both co-cultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10-6 cm.sec-1, where these values for BBCECs were ~25 and ~5 (×10-6 cm.sec-1. Conclusion: Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.

  4. Support vector machines for seizure detection in an animal model of chronic epilepsy

    Science.gov (United States)

    Nandan, Manu; Talathi, Sachin S.; Myers, Stephen; Ditto, William L.; Khargonekar, Pramod P.; Carney, Paul R.

    2010-06-01

    We compare the performance of three support vector machine (SVM) types: weighted SVM, one-class SVM and support vector data description (SVDD) for the application of seizure detection in an animal model of chronic epilepsy. Large EEG datasets (273 h and 91 h respectively, with a sampling rate of 1 kHz) from two groups of rat