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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. Porcine Ex Vivo intestinal segment model

    OpenAIRE

    Ripken, D.; Hendriks, H.F.J.

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Compared to the Ussing chamber (Chap. 24) the porcine ex vivo small intestinal segment model is a relatively simple to use intestinal tissue model. The main difference being that the tissue segment is not...

  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

    Science.gov (United States)

    Jansen of Lorkeers, Sanne J.; Gho, Johannes M. I. H.; Koudstaal, Stefan; van Hout, Gerardus P. J.; Zwetsloot, Peter Paul M.; van Oorschot, Joep W. M.; van Eeuwijk, Esther C. M.; Leiner, Tim; Hoefer, Imo E.; Goumans, Marie-José; Doevendans, Pieter A.; Sluijter, Joost P. G.; Chamuleau, Steven A. J.

    2015-01-01

    Background 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. Aim 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. Methods & Results 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. Conclusion 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. PMID:26678993

  5. 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.

    Directory of Open Access Journals (Sweden)

    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.

  6. Porcine Ex Vivo intestinal segment model

    NARCIS (Netherlands)

    Ripken, D.; Hendriks, H. F J

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Compare

  7. Porcine Ex Vivo intestinal segment model

    NARCIS (Netherlands)

    Ripken, D.; Hendriks, H.F.J.

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Comp

  8. Latent porcine circovirus type 2-infected domestic pigs: A potential infection model for the effective development of vaccines against latent or chronic virus induced diseases.

    Science.gov (United States)

    Sydler, Titus; Brägger, Stefanie; Handke, Martin; Hartnack, Sonja; Lewis, Fraser I; Sidler, Xaver; Brugnera, Enrico

    2016-02-17

    Until recently, knowledge of the pathogenicity of Circoviridae and Anelloviridae family members was limited. Our previous discoveries provided clues toward resolving this issue based on studies of the latent nature of porcine circovirus type 2 (PCV2) genotype group members. We developed a conventional pig infection model that indicated that weaners already harbored latent PCV2 infection in the thymus, which enabled the viruses to specifically modulate the maturation of T-helper cells. This finding raised the possibility that the thymi of normal fetuses were already infected with PCV2. The present findings further substantiate our hypothesis that PCV2 masquerades as the host by infecting fetuses before they acquire immune-competence. We provide the first demonstration that all domestic pig fetuses preferentially harbor latent PCV2-infected cells in their thymi. These PCV2-infected cells are different from thymocytes and are located in the medulla of the fetal thymus. These latent PCV2-infected cells in fetuses are found at the same location and share characteristics with the infected cells observed in adolescent pigs. Moreover, fetuses also harbor these infected cells in other lymph system organs. We provide the first demonstration that the fetal thymus virus pools are minimally affected by sow vaccination, highlighting the immune-privileged character of this organ. Furthermore, we found a striking reduction in virus-infected cells in the fetal spleen and an increase in PCV2-infected cells in the fetal intestine of anti-PCV2-vaccinated mothers. These data indicate that specific immune response interactions occur between mothers and their progeny that are not dependent on the humoral immunity of the mother and cannot be attributed to the rudimentary humoral responses of the fetuses because these pig fetuses do not have any PCV2-specific antibodies. These shifts in our understanding of the PCV2-infected cell pool will lead to different avenues in the search for

  9. 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.

  10. 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

    OpenAIRE

    Jansen of Lorkeers, SJ; Gho, Johannes M. I. H.; Koudstaal, Stefan; van Hout, Geert; Zwetsloot, Peter Paul M; van Oorschot, Joep W M; Esther C M van Eeuwijk; Leiner, Tim; Höfer, Imo E.; Goumans, Marie-José; Doevendans, Pieter A.; Sluijter, Joost P. G.; Chamuleau, Steven A J

    2015-01-01

    BACKGROUND: 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. AIM: 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 tra...

  11. Tissue Sampling Guides for Porcine Biomedical Models.

    Science.gov (United States)

    Albl, Barbara; Haesner, Serena; Braun-Reichhart, Christina; Streckel, Elisabeth; Renner, Simone; Seeliger, Frank; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-04-01

    This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. PMID:26883152

  12. 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...

  13. A Simple Porcine Model of Inducible Sustained Atrial Fibrillation.

    Science.gov (United States)

    Lee, Anson M; Miller, Jacob R; Voeller, Rochus K; Zierer, Andreas; Lall, Shelly C; Schuessler, Richard B; Damiano, Ralph J; Melby, Spencer J

    2016-01-01

    The surgical management of atrial fibrillation (AF) is an evolving field with a history of testing various lesion sets and ablation technologies. Previous animal models of AF require a chronic intervention to make AF reliably inducible. Our objective was to create an acute, reliable, and reproducible porcine model of sustained AF. To accomplish this, 21 adult domestic pigs underwent median sternotomy. Methods to induce AF were then performed sequentially: manual stimulation, rapid pacing (200 beats per minute), and then rapid pacing of 8 beats with a cycle length of 300 milliseconds, followed by an extra stimulus at decreasing cycle lengths. If AF was not induced, burst pacing was performed at a cycle length of 90 milliseconds for 30 seconds. If AF was still not induced, intravenous neostigmine was administered, and the process was repeated. Atrial fibrillation was considered sustained after 1 minute. Attempts at AF induction were successful in 18 (86%) of 21. Atrial fibrillation was induced during manual stimulation in four (19%), during rapid pacing in five (24%), during burst pacing in five (24%), and after the administration of neostigmine in four (19%). Mean (SD) duration of AF was 3.6 (2.6) minutes. Of the 18, 14 (78%) reverted to sinus rhythm spontaneously and 4 (22%) required an antiarrhythmic. This technique of inducing AF can easily be used to evaluate new technologies and lesion sets without the need for creating a chronic animal model. PMID:26889882

  14. Three dimensional fusion of electromechanical mapping and magnetic resonance imaging for real-time navigation of intramyocardial cell injections in a porcine model of chronic myocardial infarction.

    Science.gov (United States)

    van Slochteren, F J; van Es, R; Gyöngyösi, M; van der Spoel, T I G; Koudstaal, S; Leiner, T; Doevendans, P A; Chamuleau, S A J

    2016-05-01

    For cardiac regenerative therapy intramyocardial catheter guided cell transplantations are targeted to the infarct border zone (IBZ) i.e. the closest region of viable myocardium in the vicinity of the infarct area. For optimal therapeutic effect this area should be accurately identified. However late gadolinium enhanced magnetic resonance imaging (LGE-MRI) is the gold standard technique to determine the infarct size and location, electromechanical mapping (EMM) is used to guide percutaneous intramyocardial injections to the IBZ. Since EMM has a low spatial resolution, we aim to develop a practical and accurate technique to fuse EMM with LGE-MRI to guide intramyocardial injections. LGE-MRI and EMM were obtained in 17 pigs with chronic myocardial infarction created by balloon occlusion of LCX and LAD coronary arteries. LGE-MRI and EMM datasets were registered using our in-house developed 3D CartBox image registration software toolbox to assess: (1) the feasibility of the 3D CartBox toolbox, (2) the EMM values measured in the areas with a distinct infarct transmurality (IT), and (3) the highest sensitivity and specificity of the EMM to assess IT and define the IBZ. Registration of LGE-MRI and EMM resulted in a mean error of 3.01 ± 1.94 mm between the LGE-MRI mesh and EMM points. The highest sensitivity and specificity were found for UV <9.4 mV and bipolar voltage <1.2 mV to respectively identify IT of ≥5 and ≥97.5 %. The 3D CartBox image registration toolbox enables registration of EMM data on pre-acquired MRI during the EMM guided procedure and allows physicians to easily guide injections to the most optimal injection location for cardiac regenerative therapy and harness the full therapeutic effect of the therapy. PMID:26883433

  15. Porcine survival model to simulate acute upper gastrointestinal bleedings.

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    Prosst, Ruediger L; Schurr, Marc O; Schostek, Sebastian; Krautwald, Martina; Gottwald, Thomas

    2016-06-01

    The existing animal models used for the simulation of acute gastrointestinal bleedings are usually non-survival models. We developed and evaluated a new porcine model (domestic pig, German Landrace) in which the animal remains alive and survives the artificial bleeding without any cardiovascular impairment. This consists of a bleeding catheter which is implanted into the stomach, then subcutaneously tunnelled from the abdomen to the neck where it is exteriorized and fixed with sutures. Using the injection of porcine blood, controllable and reproducible acute upper gastrointestinal bleeding can be simulated while maintaining normal gastrointestinal motility and physiology. Depending on the volume of blood applied through the gastric catheter, the bleeding intensity can be varied from traces of blood to a massive haemorrhage. This porcine model could be valuable, e.g. for testing the efficacy of new bleeding diagnostics in large animals before human use. PMID:26306615

  16. Cardiac dysfunction in a porcine model of pediatric malnutrition

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Lykke, Mikkel; Nielsen, Anne-Louise Hother; Koch, Jørgen; Nielsen, Ole Bækgaard; Hunter, Ingrid; Goetze, Jens P.; Friis, Henrik; Thymann, Thomas

    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...... 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). CONCLUSIONS: Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro...

  17. A porcine model of haematogenous brain infectionwith staphylococcus aureus

    DEFF Research Database (Denmark)

    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...... inserted surgically, one in a. carotis communis and one in v. jugularis externa. All pigs received 106 CFU/kg body weight S. aureus through the arterial catheter. Bacteria were either suspended in isotonic saline infused at constant flow for 60 minutes (two pigs) or given as a bolus injection of autologoue...

  18. Porcine neuronal models that recapitulate HD pathogenesis in vitro

    Czech Academy of Sciences Publication Activity Database

    Hruška-Plocháň, Marian; Vodička, Petr; Lacková, Monika; Usvald, Dušan; Juhás, Štefan; Hrdličková, R.; Miyanohara, A.; Maršala, M.; Motlík, Jan

    Vol. P 50. Milano: Keyword Europa, 2009, s. 32-32. [IV. Meeting on the molecular mechanisms of neurodegeneration. Miláno (IT), 08.05.2009-10.05.2009] R&D Projects: GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50450515 Keywords : Huntington disease * porcine neuronal model Subject RIV: FH - Neurology

  19. Porcine incisional hernia model: Evaluation of biologically derived intact extracellular matrix repairs

    OpenAIRE

    Monteiro, Gary A; Delossantos, Aubrey I.; Rodriguez, Neil L.; Patel, Paarun; Franz, Michael G.; Wagner, Christopher T.

    2013-01-01

    We compared fascial wounds repaired with non-cross-linked intact porcine-derived acellular dermal matrix versus primary closure in a large-animal hernia model. Incisional hernias were created in Yucatan pigs and repaired after 3 weeks via open technique with suture-only primary closure or intraperitoneally placed porcine-derived acellular dermal matrix. Progressive changes in mechanical and biological properties of porcine-derived acellular dermal matrix and repair sites were assessed. Porcin...

  20. Functional Characterization of a Porcine Emphysema Model

    DEFF Research Database (Denmark)

    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...... phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12−/− mice are protected from smoke-induced emphysema. ITGB6−/− mice spontaneously...... 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...

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

    DEFF Research Database (Denmark)

    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 nonruminan...... 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.......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...

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

    OpenAIRE

    Bishop, James H.; James R Fox; 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 experime...

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

    DEFF Research Database (Denmark)

    Gao, H; Sandermann, J; Prag, J; Lund, L; Lindholt, Jes S.

    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....

  4. Microsurgical cerebral aneurysm training porcine model

    Directory of Open Access Journals (Sweden)

    Jon Olabe

    2011-01-01

    Full Text Available The authors developed a simple reproducible technique for aneurysm creation and adapted it to mimic intracranial dissection conditions using glue application as a pseudo-arachnoid type layer. Ten 1-2-month-old healthy domestic swine were employed under general anesthesia. A novel technique for bifurcation aneurysm creation was developed using two arteries and a vein. After aneurysm creation, diluted sulfuric acid was applied on the dome with a micropipette to increase aneurysm fragility in selected zones. The surgical field was then dried and contact glue was applied around the vascular complex in a circular manner so as to emulate arachnoidal connection fibers. Microsurgical dissection of the aneurysm and surrounding vessels was performed by delicately removing the adhesive substance. Diverse aneurysm clipping techniques, emergency rupture situations and vascular reconstruction procedures were trained. Twenty-two aneurysms were created at several vascular sites, one aneurysm dome ruptured during application of sulfuric acid, two aneurysm models were proved to be thrombosed, two aneurysms ruptured during the dissection and no intraoperative deaths occurred. All aneurysms were clipped in an acceptable manner. This bifurcation aneurysm model provides a novel training system to be used not only by neurosurgeons but also by neurovascular interventionists.

  5. 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.

  6. 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.

  7. Study of autophagic proteins in porcine HD model: pathway stimulation and differences in brain tissues

    Czech Academy of Sciences Publication Activity Database

    Kotrčová, Eva; Hrabáková, Rita; Jarkovská, Karla; Juhásová, Jana; Motlík, Jan

    Mělník: IAPG, 2013. [Large Animal Models of Neurodegenerative Diseases /2./. 17.11.2013-19.11.2013, Liblice] Institutional support: RVO:67985904 Keywords : porcine HD model Subject RIV: FH - Neurology

  8. 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.

  9. Biphasic presence of fibrocytes in a porcine hypertrophic scar model.

    Science.gov (United States)

    Travis, Taryn E; Mino, Matthew J; Moffatt, Lauren T; Mauskar, Neil A; Prindeze, Nicholas J; Ghassemi, Pejhman; Ramella-Roman, Jessica C; Jordan, Marion H; Shupp, Jeffrey W

    2015-01-01

    The duroc pig has been described as a promising animal model for use in the study of human wound healing and scar formation. However, little is known about the presence and chronology of the fibrocyte cell population in the healing process of these animals. Wounds known to form scar were created on red duroc swine (3" x 3") with a dermatome to a total depth of either 0.06 inches or 0.09 inches. These wounds were allowed to heal completely and biopsies were done at scheduled time points during the healing process. Biopsies were formalin fixed and paraffin embedded for immunohistochemical analysis. Porcine reactive antibodies to CD-45 and procollagen-1 and a human reactive antibody to LSP-1 were used to detect the presence of fibrocytes in immunohistochemistry, an immunocytochemistry. Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06 inches deep wounds showed positive staining for CD-45 and LSP-1 within highly cellular areas at days 2 and 4 after wounding. Additional animals with 0.09 inches deep wounds showed positive staining within similar areas at days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining was diffused in all samples. Cultured cells were stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. These data confirm that fibrocytes are indeed present in this porcine model. We conclude that these cells are present after initial wounding and later during scar formation and remodeling. We believe that this is an evidence of a biphasic presence of fibrocytes, first as an acute response to skin wounding followed by later involvement in the remodeling process, prompted by continued inflammation in a deep partial thickness wound. PMID:25051518

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

    OpenAIRE

    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 changes in color of porcine lean meat batters (PLMBs) during processing were characterized, analyzed, and predicted using graphical analysis, kinetic analysis, and mathematical modeling respectively. "A...

  11. Surgical induction of choroidal neovascularization in a porcine model

    DEFF Research Database (Denmark)

    Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik; Qvortrup, Klaus; Scherfig, Erik; la Cour, Morten

    2007-01-01

    PURPOSE: To develop a reproducible surgical technique for the induction of choroidal neovascularization (CNV) in the subretinal space of porcine eyes and to analyse the resulting CNV clinically and histologically. METHODS: Two different modifications of a surgical technique previously described...... 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 by a...... single perforation of Bruch's membrane. Fifteen of the eyes, five from each group, were enucleated 30 minutes after surgery, while the remaining eyes were enucleated after 14 days. Prior to enucleation, at day 14, fundus photographs and fluorescein angiograms were obtained. Eyes were examined by light...

  12. Possibilities of microscopic detection of isolated porcine proteins in model meat products

    Directory of Open Access Journals (Sweden)

    Michaela Petrášová

    2016-05-01

    Full Text Available In recent years, various protein additives intended for manufacture of meat products have increasing importance in the food industry. These ingredients include both, plant-origin as well as animal-origin proteins. Among animal proteins, blood plasma, milk protein or collagen are used most commonly. Collagen is obtained from pork, beef, and poultry or fish skin. Collagen does not contain all the essential amino acids, thus it is not a full protein in terms of essential amino acids supply for one's organism. However, it is rather rich in amino acids of glycine, hydroxyproline and proline which are almost absent in other proteins and their synthesis is very energy intensive. Collagen, which is added to the soft and small meat products in the form of isolated porcine protein, significantly affects the organoleptic properties of these products. This work focused on detection of isolated porcine protein in model meat products where detection of isolated porcine protein was verified by histological staining and light microscopy. Seven model meat products from poultry meat and 7 model meat products from beef and pork in the ratio of 1:1, which contained 2.5% concentration of various commercially produced isolated porcine proteins, were examined. These model meat products were histologically processed by means of cryosections and stained with hematoxylin-eosin staining, toluidine blue staining and Calleja. For the validation phase, Calleja was utilized. To determine the sensitivity and specificity, five model meat products containing the addition of isolated porcine protein and five model meat products free of it were used. The sensitivity was determined for isolated porcine protein at 1.00 and specificity was determined at 1.00. The detection limit of the method was at the level of 0.001% addition. Repeatability of the method was carried out using products with addition as well as without addition of isolated porcine protein and detection was repeated

  13. Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia

    DEFF Research Database (Denmark)

    Granfeldt, Asger

    Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia American Heart Scientific sessions Resuscitation Science symposium 16-20 November......Cardioprotective and anti-inflammatory effects of treatment with Adenocaine/Mg2+ in a porcine model of endotoxemia American Heart Scientific sessions Resuscitation Science symposium 16-20 November...

  14. Robotically assisted laparoscopic tubal anastomosis in a porcine model: a pilot study.

    Science.gov (United States)

    Margossian, H; Garcia-Ruiz, A; Falcone, T; Goldberg, J M; Attaran, M; Miller, J H; Gagner, M

    1998-04-01

    As with standard microsurgical procedures performed at laparotomy, laparoscopic tubal anastomosis requires great dexterity. Handling fine suture materials under magnification to anastomose tubal segments with lumens less than 3 mm in diameter while working with your hands at a distance from the tissue makes these fine movements even more difficult. This is exacerbated by the tremor induced by the fatigue caused by a prolonged laparoscopic procedure and the need for precise control. We conducted a pilot study to evaluate the feasibility of performing laparoscopic tubal anastomosis with robotic assistance in a live porcine model. Two anastomoses were performed on one uterine horn via each of the following techniques: laparoscopy, laparoscopy with robotic assistance, and open microsurgery. Immediate necropsy demonstrated all the anastomoses to be patent. There were no intraoperative complications. Laparoscopic tubal anastomosis was associated with surgeon fatigue and neck, shoulder, and back pain. The surgeons were more comfortable performing the procedure with robotic assistance. The device functioned well and without incident. This acute animal study suggests that robotic assistance in laparoscopic tubal anastomoses is safe and feasible. It enhances surgeons' dexterity and precision while reducing fatigue. It is promising for future use in chronic experimental studies. PMID:9617965

  15. 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 with...

  16. Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium.

    Directory of Open Access Journals (Sweden)

    Silke S Zakrzewski

    Full Text Available Cell lines matching the source epithelium are indispensable for investigating porcine intestinal transport and barrier properties on a subcellular or molecular level and furthermore help to reduce animal usage. The porcine jejunal cell line IPEC-J2 is established as an in vitro model for porcine infection studies but exhibits atypically high transepithelial resistances (TER and only low active transport rates so that the effect of nutritional factors cannot be reliably investigated. This study aimed to properly remodel IPEC-J2 and then to re-characterize these cells regarding epithelial architecture, expression of barrier-relevant tight junction (TJ proteins, adequate TER and transport function, and reaction to secretagogues. For this, IPEC-J2 monolayers were cultured on permeable supports, either under conventional (fetal bovine serum, FBS or species-specific (porcine serum, PS conditions. Porcine jejunal mucosa was analyzed for comparison. Main results were that under PS conditions (IPEC-J2/PS, compared to conventional FBS culture (IPEC-J2/FBS, the cell height increased 6-fold while the cell diameter was reduced by 50%. The apical cell membrane of IPEC-J2/PS exhibited typical microvilli. Most importantly, PS caused a one order of magnitude reduction of TER and of trans- and paracellular resistance, and a 2-fold increase in secretory response to forskolin when compared to FBS condition. TJ ultrastructure and appearance of TJ proteins changed dramatically in IPEC-J2/PS. Most parameters measured under PS conditions were much closer to those of typical pig jejunocytes than ever reported since the cell line's initial establishment in 1989. In conclusion, IPEC-J2, if cultured under defined species-specific conditions, forms a suitable model for investigating porcine paracellular intestinal barrier function.

  17. 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.

  18. The effect of dietary fatty acids on post-operative inflammatory response in a porcine model

    DEFF Research Database (Denmark)

    Langerhuus, Sine Nygaard; Jensen, Karin Hjelholt; Tønnesen, Else Kirstine;

    2012-01-01

    ), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 < day ≤ 3), FO suppressed whole blood IL-8 and tumor necrosis factor...

  19. 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

  20. Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model

    NARCIS (Netherlands)

    Ahmed, M.; Anninga, Bauke; Pouw, J.J.; Vreemann, S.; Peek, M.; Hemelrijck, van Mieke; Pinder, Sara E.; Haken, ten B.; Pankhurst, Quentin A.; Douek, Michael

    2015-01-01

    The magnetic technique for sentinel lymph node biopsy (SLNB) has been evaluated in several clinical trials. An in vivo porcine model was developed to optimise the magnetic technique by evaluating the effect of differing volume, concentration and time of injection of magnetic tracer. A total of 60 se

  1. Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

    DEFF Research Database (Denmark)

    Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars;

    2013-01-01

    stimulated glucose uptake nor glycogen synthesis in insulin-resistant myotubes generated by excess glucose exposure. CONCLUSIONS: Primary porcine myotubes were established as a model of skeletal muscles for measuring glucose uptake and glycogen synthesis, and we showed that PA can play a role in stimulating...

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

    Science.gov (United States)

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

    2015-07-01

    There is increasing interest in nonrodent 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 as ischemia-reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine and mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

  3. Missing effects of zinc in a porcine model of recurrent endotoxemia

    Directory of Open Access Journals (Sweden)

    Klinge Uwe

    2005-10-01

    Full Text Available Abstract Background Chronic human sepsis often is characterised by the compensatory anti-inflammatory response syndrome (CARS. During CARS, anti-inflammatory cytokines depress the inflammatory response leading to secondary and opportunistic infections. Proved in vitro as well as in vivo, zinc's pro-inflammatory effect might overcome this depression. Methods We used the model of porcine LPS-induced endotoxemia established by Klosterhalfen et al. 10 pigs were divided into two groups (n = 5. Endotoxemia was induced by recurrent intravenous LPS-application (1.0 μg/kg E. coli WO 111:B4 at hours 0, 5, and 12. At hour 10, each group received an intravenous treatment (group I = saline, group II = 5.0 mg/kg elementary zinc. Monitoring included hemodynamics, blood gas analysis, and the thermal dilution technique for the measurement of extravascular lung water and intrapulmonary shunt. Plasma concentrations of IL-6 and TNF-alpha were measured by ELISA. Morphology included weight of the lungs, width of the alveolar septae, and rate of paracentral liver necrosis. Results Zinc's application only trended to partly improve the pulmonary function. Compared to saline, significant differences were very rare. IL-6 and TNF-alpha were predominately measured higher in the zinc group. Again, significance was only reached sporadically. Hemodynamics and morphology revealed no significant differences at all. Conclusion The application of zinc in this model of recurrent endotoxemia is feasible and without harmful effects. However, a protection or restoration of clinical relevance is not evident in our setting. The pulmonary function just trends to improve, cytokine liberation is only partly activated, hemodynamics and morphology were not influenced. Further pre-clinical studies have to define zinc's role as a therapeutic tool during CARS.

  4. A Porcine Model for Endolaparoscopic Abdominal Aortic Repair and Endoscopic Training

    OpenAIRE

    Martinez, Bernardo D.; Zarins, Christopher K.; Daunt, David A.; Coleman, Leslie A.; Saenz, Yamil; Fogarty, Thomas J.; Hermann, George D.; Nezhat, Camran R.; Olsen, Eric K.

    2003-01-01

    Objective: The goals of this laboratory model were to evaluate the performance of the surgical team and endolaparoscopic techniques in the porcine model of infrarenal abdominal aortic repair. Methods: Twenty-four pigs underwent full endolaparoscopic aorto-aortic graft implantation with voice-activated computerized robotics. The first group of 10 pigs (acute) was sacrificed while under anesthesia at 0.5 hours (5 animals) and 2 hours (5 animals). The second group of 14 pigs (survival) were reco...

  5. 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. PMID:26416815

  6. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells

    Science.gov (United States)

    Di Lauro, Salvatore; Rodriguez-Crespo, David; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, J. Carlos; Srivastava, Girish K.

    2016-01-01

    Purpose To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. Methods RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. Results Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. Conclusions A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies. PMID:27081295

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

    Institute of Scientific and Technical Information of China (English)

    Cai-Jun Wu; Zhi-Jun Guo; Chun-Sheng Li; Yi Zhang; Jun Yang

    2015-01-01

    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 ofCPR.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.

  8. 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.

  9. 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...... developed microabscesses in bones of the infected legs. In the centre of microabscesses, S. aureus was regularly demonstrated together with necrotic neutrophils. Often, bone lesions resulted in trabecular osteonecrosis. The present localized model of acute haematogenous osteomyelitis revealed a pattern of...

  10. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    OpenAIRE

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H. S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen; Caplice, Noel M.

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for...

  11. A new lung stent tested as fiducial marker in a porcine model

    International Nuclear Information System (INIS)

    Introduction: The aim of the present study was to test the feasibility of a Nickel–Titanium (Ni–Ti) stent technique (Memocore™) in a porcine model. The stent is intended as a new fiducial for gated image guided radiotherapy in the lung. The study included test of an improved insertion system and respiratory gated treatments with this new technique. Methods and materials: Tests were carried out in a porcine model using Göttingen mini-pigs. The study included 10 animals. Planning CT was performed as 4 dimensional CT (4DCT) using the Varian RPM system. Respiratory gated radiotherapy treatments were simulated using the Brainlab ExacTrac system. Reproducibility of stent position during treatment was analyzed off-line using an experimental version of the ExacTrac software. The experimental version has a dedicated algorithm for segmentation of the stent in the planning CT and subsequent registration to X-ray position images. Results: A total of 23 stents were inserted in the 10 animals. Stents could be placed in all parts of the lungs. No stent migrated within the four weeks the experiment lasted. Stent trajectories in the lung were not reproducible, even though respiration was highly standardized using a respirator. The best accuracy of stent position in the gating window was obtained using gating at the halfmax amplitude as reference level. The smallest stent movement within the gating window was observed in the exhale phase. Further success of human application will depend on the possibility to insert the stent within or close to lung tumors. Conclusions: This new technique based on the Memocore™ lung stent used in connection with respiratory gated radiotherapy was demonstrated to be feasible in a porcine model. The study demonstrated lack of reproducibility in lung trajectories of inserted stents. The technique gave the best accuracy when applied to the exhale phase of respiration.

  12. Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model.

    OpenAIRE

    Izbicki, J. R.; Raedler, C; Anke, A; Brunner, P; Siebeck, M; Leinisch, E; Lüttiken, R; Ruckdeschel, G; Wilker, D. K.; Schweiberer, L

    1991-01-01

    In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or with liposomes alone. After 24 h each animal received an injection of either 10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800) leukocytes per mm3 a...

  13. A novel device to create consistent deep dermal burns in a porcine model

    OpenAIRE

    Menon, Seema; Chan, Queenie; Bertinetti, Monique; Harvey, John G; Hei, Erik R La; Holland, Andrew JA

    2016-01-01

    We conducted this study to evaluate a novel device to create a consistent and reproducible deep partial thickness burn in a porcine model. A thermostatically controlled, heated aluminium disc device was fashioned by the Biomedical Department of our institution. Contact burns were made on the flank of two Great White pigs by applying the device heated to 92°C at intervals of 5, 10, 15 and 20 seconds to four separate test areas area of skin. Biopsies for histological analysis of burn depth were...

  14. Anti-Inflammatory Effects of Mannanase-Hydrolyzed Copra Meal in a Porcine Model of Colitis

    OpenAIRE

    IBUKI, Masahisa; FUKUI, Kensuke; KANATANI, Hiroyuki; Mine, Yoshinori

    2014-01-01

    ABSTRACT We evaluated the anti-inflammatory activity of mannanase-hydrolyzed copra meal (MNB), including β-1,4-mannobiose (67.8%), in a dextran sodium sulfate (DSS)-induced porcine model of intestinal inflammation. In the DSS-positive control (POS) and MNB treatment (MCM) groups, DSS was first administered to piglets via intragastric catheter for 5 days, followed by 5 days administration of saline or MCM. A negative control group (NEG) received a saline alternative to DSS and MNB. Inflammatio...

  15. Spermatozoa immunophenotype markers associated with porcine HD model

    Czech Academy of Sciences Publication Activity Database

    Klíma, Jiří; Vochozková, Petra; Juhásová, Jana; Bohuslavová, Božena; Mačáková, Monika; Motlík, Jan; Juhás, Štefan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 17-17. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : spermatozoa Subject RIV: FH - Neurology

  16. Laparoscopic colonic anastomosis using a degradable stent in a porcine model

    Science.gov (United States)

    Ma, Liang; Cai, Xiu-Jun; Wang, Hai-Hong; Yu, Yan-Lan; Huang, Di-Yu; Ge, Guang-Ju; Hu, Hai-Yi; Yu, Shi-Cheng

    2016-01-01

    AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model. PMID:27217702

  17. Resident Education in Principles and Technique of Bowel Surgery Using an Ex-Vivo Porcine Model

    Directory of Open Access Journals (Sweden)

    M. Bijoy Thomas

    2010-01-01

    Full Text Available Objective. improve competency of residents with lysis of adhesion (LOA and bowel surgery using a porcine model. Study Design. Pig bowel was removed at time of an anatomy laboratory, cleansed, and used to demonstrate surgical techniques and principles of LOA, repair of enterotomy, bowel resection, and anastomosis. Participants were surveyed pre- and posttraining session using 10 point Likert scale. Results. Thirty one residents at varying levels of training participated. After the training session, there was a significant improvement noted in mean scores for comfort level with LOA (6.3 versus 7.7, =.007, comfort level with enterotomy repair (2.8 versus 6.4, <.0001, understanding principles of LOA (5.0 versus 7.7, <.0001, understanding principles of enterotomy repair (3.5 versus 7.0, <.0001, and familiarity with instruments used (5.8 versus 7.3, =.01. Conclusion. Training sessions using ex-vivo porcine model improve resident perception of knowledge and comfort with LOA and enterotomy repair.

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

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard

    . However, a number of genes in the liver (six out of 26 genes) were down-regulated, which is not like the human response to obesity. When comparing the three breeds of porcine obesity-models with regards to the acute phase protein ORM, none of the three breeds showed any difference in the gene regulation...... 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...... response to obesity-induced inflammation were examined to define the response and to identify a pig model that resembles the human response. Regulation was examined in the liver, two adipose tissues from the abdomen (subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal adipose tissue (RPAT...

  19. Immunohistochemistry of porcine skin.

    Science.gov (United States)

    Wollina, U; Berger, U; Mahrle, G

    1991-01-01

    The present paper reports immunohistological findings in porcine skin, which were obtained by use of mono- and polyclonal antihuman antibodies and either alkaline phosphatase anti-alkaline phosphatase (APAAP) or peroxidase (POX) technique. Epidermal staining was observed with antibodies to keratins (K 8.12, RSKE 60), filaggrin, and calmodulin (ACAM). Staining of connective tissue and vessels was achieved using antibodies to vimentin (V9(1)), collagen type IV, and fibronectin. In general, these antibodies gave a staining pattern similar to that of normal human skin. The similarities of immunoreactivity to poly- and monoclonal antihuman antibodies in porcine and human skin render porcine skin a reliable model in biomedical research. PMID:1710864

  20. Establishment of a porcine model of patent foramen ovale

    International Nuclear Information System (INIS)

    Objective: To investigate the feasibility of developing an animal model of patent foramen ovale (PFO) in piglets by percutaneous atrial septal puncture and balloon dilation. Methods: A standardized percutaneous atrial trans-septal puncture and balloon dilation was conducted in eleven healthy piglets under general anesthesia. A Rups-100 system inserted through a femoral vein was used for the trans-septal puncture, and subsequent balloon dilatation was performed at the puncture site to imitate a PFO. Euthanasia and autopsy were performed on day-1 in 1 piglet (early autopsy), and on day-21 in the remaining 10 piglets (late autopsy). Results: Artificial PFO was successfully created in all piglets and verified by fluoroscopy. No major technical difficulty or complication was encountered except in one which developed mild hemopericardium. In the piglet which had early autopsy, the artificial foramen was measured 0.8 cm x 0.7 cm in cross-section and aggregates of erythrocytes were revealed over its rim under light microscopy. In the late autopsy group (n=10), 7 piglets had the created foramens healed and sealed off; while the other 3 showed relatively small residual lumens measuring 0.1 cm x 0.2 cm, 0.2 cm x 0.2 cm and 0.1 cm x 0.3 cm in cross-section respectively. Histological examination of specimens from the late autopsy group showed variable neointima hyperplasia, loss of neointima, infiltration of lymphocytes, focal hydropic degeneration of cardiac muscle, and focal fibrosis of interstitium at the immediate vicinity of regardless of the course of healing. Conclusion: Artificial creation of PFO in piglets is feasible by percutaneous atrial septal puncture and balloon dilation. This protocol may serve as a research model for PFO-related stroke in human. (authors)

  1. 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. PMID:22444086

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

    Science.gov (United States)

    Zhou, Zhen-hua; Peng, Jing; Meng, Zhao-you; Chen, Lin; Huang, Jia-Lu; Huang, He-qing; Li, Li; Zeng, Wen; Wei, Yong; Zhu, Chu-Hong; Chen, Kang-Ning

    2016-01-01

    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-pyridyldithiol)propionate 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. PMID:27540277

  3. Porcine Heterotopic Composite Tissue Allograft Transplantation using A Large Animal Model for Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Yur-Ren Kuo

    2006-06-01

    Full Text Available Background: Composite tissue allograft (CTA transplantation is currently limited by therisks of side effects resulting from long-term high-dose immunosuppression.Therefore, preclinical animal models are essential to help CTA transplantationadvance into clinical reality. Evidence has shown that small-animalmodel (rodents immunotherapy protocols cannot be directly applied tohumans. This study investigated whether a miniature porcine model is reproduciblefor preclinical studies.Methods: Based on the concept of vascularized skeletal tissue allograft transplantation,limb heterotopic allograft tissue from a mismatched donor miniature pig consistingof the distal femur, knee joint, tibia, fibula, and surrounding musclewith a vascularized skin paddle model supplied by the superficial femoralvessels was transplanted into recipient pigs. Swine viability and rejectionsigns of the allograft were monitored postoperatively. Histopathologicalchanges in the allograft tissues were examined using hematoxylin and eosinstaining if the allo-skin flap was rejected.Results: The recipient pigs were ambulatory immediately following surgery. Theflaps showed no visible signs of rejection over the first 4 days of observation.The skin flaps appeared bluish-purple and edematous on postoperative days5~7, and progressed to tissue necrosis and rejection on postoperative days8~13. Histological examination revealed marked mononuclear cell infiltrationand necrotic changes in the all rejected tissues, especial in the allograftskin tissues (skin > muscle > bone > cartilage.Conclusions: The results showed this the porcine CTA model is reproducible and suitablefor preclinical training for human CTA transplantation. Monitoring of theallo-skin flap is a useful strategy to evaluate composite tissue allograft rejection.

  4. 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.

    2015-03-01

    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.

  5. Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

    International Nuclear Information System (INIS)

    Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent “pores” in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

  6. Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

    DEFF Research Database (Denmark)

    Sørensen, Nina Buus; Lassota, Nathan; Kyhn, Maria Voss;

    2013-01-01

    BACKGROUND: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases...... brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. RESULTS: The mfERG P1 amplitude was decreased 2 weeks (T2....... CONCLUSION: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG....

  7. 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

    -renal aorta exposed by laparotomy; “CLEAN” pigs had an aortic graft inserted; “LOW” and “HIGH” pigs had an aortic graft inserted and, subsequently, S. aureus were inoculated on the graft material (5 × 104 colony-forming units [CFU] and 1 × 106 CFU, respectively). Biomarkers were evaluated prior to surgery...... and on day 2, 5, 7, and 14 post-operatively in blood samples. Of all biomarkers evaluated, CRP was superior for diagnosing S. aureus AVPGI in pigs, with a sensitivity of 0.86 and a specificity of 0.75.......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...

  8. Experimental validation of a new biphasic model of the contact mechanics of the porcine hip.

    Science.gov (United States)

    Li, Junyan; Wang, Qianqian; Jin, Zhongmin; Williams, Sophie; Fisher, John; Wilcox, Ruth K

    2014-05-30

    Hip models that incorporate the biphasic behaviour of articular cartilage can improve understanding of the joint function, pathology of joint degeneration and effect of potential interventions. The aim of this study was to develop a specimen-specific biphasic finite element model of a porcine acetabulum incorporating a biphasic representation of the articular cartilage and to validate the model predictions against direct experimental measurements of the contact area in the same specimen. Additionally, the effect of using a different tension-compression behaviour for the solid phase of the articular cartilage was investigated. The model represented different radial clearances and load magnitudes. The comparison of the finite element predictions and the experimental measurement showed good agreement in the location, size and shape of the contact area, and a similar trend in the relationship between contact area and load was observed. There was, however, a deviation of over 30% in the magnitude of the contact area, which might be due to experimental limitations or to simplifications in the material constitutive relationships used. In comparison with the isotropic solid phase model, the tension-compression solid phase model had better agreement with the experimental observations. The findings provide some confidence that the new biphasic methodology for modelling the cartilage is able to predict the contact mechanics of the hip joint. The validation provides a foundation for future subject-specific studies of the human hip using a biphasic cartilage model. PMID:24878736

  9. Radiofrequency thermal ablation of benign cystic lesion: an experimental pilot study in a porcine gallbladder model

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Taek; Rhim, Hyun Chul; Choi, Jung Bin; Oh, Jae Cheon; Cho, On Koo; Koh, Byung Hee; Kim, Yong Soo; Seo, Heung Suk; Joo, Kyung Bin [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-05-01

    To determine whether radiofrequency thermal ablation can be used to treat benign cystic lesions in a porcine gallbladder model. This experimental study of radiofrequency thermal ablation involved the use of 15 exvivo porcine gallbladders and 15-G expandable needle electrodes. To investigate optimal temperature parameters, three groups of five were designated according to target temperature:Group A: 70 deg C; Group B: 80 deg C; Group C: 90 deg C. After the target temperature was reached, ablation lasted for one minute. Gallbladder width, height and length were measured before and after ablation , and the estimated volume reduction ratios of the three groups were compared. Whether adjacent liver parenchyma around the gallbladder fossa was ablated by heat conducted from hot bile was also determined, and the thickness of the ablated area of the liver was measured. The volume reduction ratio in Group A, B and C was 42.7%, 41.7% and 42.9%, respectively ({rho}>.05). In all 15 cases, gallbladder walls lost their transparency and elasticity at about 70 deg C. In nine of ten cases in Groups B and C, the hepatic capsule around the gallbladder fossa was retracted at about 80 deg C. The mean thickness of liver parenchymal damage adjacent to the gallbladder was 5.4 mm in Group B and 9.8 mm in Group C. In Group A livers, only one case showed minimal gradual parenchymal change. Microscopically, all three groups showed complete coagulation necrosis of the wall. On the basis of this feasibility study, radiofrequency thermal ablation is potentially suitable for the ultrasound-guided treatment of symptomatic cystic lesions including benign hepatic or renal cyst.

  10. Animal models for investigating chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Aghdassi Alexander A

    2011-12-01

    Full Text Available Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed.

  11. Animal models for investigating chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Alexander A; Mayerle, Julia; Christochowitz, Sandra; Weiss, Frank U; Sendler, Matthias; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

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

    International Nuclear Information System (INIS)

    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.

  13. 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.

  14. Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

    Institute of Scientific and Technical Information of China (English)

    Lian-Xing Zhao; Chun-Sheng Li; Jun Yang; Nan Tong; Hong-Li Xiao; Le An

    2016-01-01

    Background:The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low.Furthermore,there are no large animal models that simulate clinical CA.The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation.Methods:This model was induced in castrated male pigs (30 ± 2 kg;n =21) by injecting thrombi (10-15 ml) via the left external jugular vein.Computed tomographic pulmonary angiography (CTPA) was performed at baseline,CA,and return of spontaneous circulation (ROSC).After CTPA during CA,cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated.Hemodynamic,respiratory,and blood gas data were monitored.Cardiac troponins T,cardiac troponin I,creatine kinase-MB,myoglobin,and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay.Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance.Results:Seventeen animals achieved CA after emboli injection,while four achieved CA after 5-8 ml more thrombi.Nine animals survived 6 h after CPR.CTPA showed obstruction of the pulmonary arteries.Mean aortic pressure data showed occurrence of CA caused by PTE (Z =-2.803,P =0.002).The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t =6.315,P =0.000,variation coefficient =0.25),and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t =27.240,P =0.000).After ROSC (n =9),heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR,P =0.036;MRVP,P =0.027).Myoglobin was statistically increased from CA to 1 h after ROSC (P =0.036,0.026,0.009,respectively),and BNP was increased from 2 h to 6 h after ROSC (P =0.012,0.014,0.039,respectively

  15. Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

    Science.gov (United States)

    Zhao, Lian-Xing; Li, Chun-Sheng; Yang, Jun; Tong, Nan; Xiao, Hong-Li; An, Le

    2016-01-01

    Background: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. Methods: This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10–15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. Results: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5–8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = −2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased

  16. 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

    amplified by reverse transcriptase polymerase chain reaction (RT-PCR), using oligonucleotide primers derived from in silico sequences. The porcine TOR1A cDNAs both encode a protein of 333 amino acids which shows a very high similarity to human (92%) TorsinA. Protein structure comparison of human and porcine...... dystonia. The close anatomical, physiological, genetic and biochemical resemblance between man and pig suggest that this animal may constitute an excellent model for this disease. This work reports the cloning and analysis of the porcine (Sus scrofa) homologue of TOR1A. Two porcine TOR1A cDNAs were...... of TorsinA is still largely unknown. Mutations in the TOR1A gene, primarily a 3-bp (GAG) deletion are associated with early-onset autosomal dominant torsion dystonia. Animal models may help to provide information about the underlying cellular and molecular mechanism of early-onset generalized...

  17. Production of F4 Fimbrial Adhesin in Plants: a Model for Oral Porcine Vaccine against Enterotoxigenic Escherichia coli

    OpenAIRE

    Joensuu, Jussi

    2006-01-01

    F4 fimbriae of enterotoxigenic Escherichia coli (ETEC) are highly stable multimeric structures with a capacity to evoke mucosal immune responses. With these characters F4 offer a unique model system to study oral vaccination against ETEC-induced porcine postweaning diarrhea. Postweaning diarrhea is a major problem in piggeries worldwide and results in significant economic losses. No vaccine is currently available to protect weaned piglets against ETEC infections. Transgenic plants provide an ...

  18. Heliox improves pulmonary mechanics in a pediatric porcine model of induced severe bronchospasm and independent lung mechanical ventilation

    OpenAIRE

    Orsini, Anthony J; Stefano, John L; Leef, Kathleen H; Jasani, Melinda; Ginn, Andrew; Tice, Lisa; Nadkarni, Vinay M.

    1999-01-01

    Background: A helium-oxygen gas mixture (heliox) has low gas density and low turbulence and resistance through narrowed airways. The effects of heliox on pulmonary mechanics following severe methacholine-induced bronchospasm were investigated and compared to those of a nitrogen-oxygen gas mixture (nitrox) in an innovative pediatric porcine, independent lung, mechanical ventilation model. Results: All of the lungs showed evidence of severe bronchospasm after methacholine challenge. Prospective...

  19. Effects of Ramiprilat-Coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model

    OpenAIRE

    Hong, Young Joon; Jeong, Myung Ho; Song, Sun-Jung; Sim, Doo Sun; Kim, Jung Ha; Lim, Kyung Seob; Hachinohe, Daisuke; Ahmed, Khurshid; Hwang, Seung Hwan; Lee, Min Goo; Ko, Jum Suk; Park, Keun-Ho; Yoon, Hyun Ju; Yoon, Nam Sik; Kim, Kye Hun

    2011-01-01

    Background and Objectives The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model. Subjects and Methods Pigs were randomized into two gr...

  20. Combination of Epinephrine with Esmolol Attenuates Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

    OpenAIRE

    Qian Zhang; Chunsheng Li

    2013-01-01

    BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic li...

  1. The effect of intra-abdominal hypertension incorporating severe acute pancreatitis in a porcine model.

    Directory of Open Access Journals (Sweden)

    Lu Ke

    Full Text Available INTRODUCTION: Abdominal compartment syndrome (ACS and intra abdominal hypertension(IAH are common clinical findings in patients with severe acute pancreatitis(SAP. It is thought that an increased intra abdominal pressure(IAP is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model. MEASUREMENTS AND METHODS: Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group: SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP and sham-operated group. We used a N(2 pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP, urine output, oxygenation parameters(e.g., S(vO(2, PO(2, PaCO(2, peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine were recorded. Histological examination of liver, intestine, pancreas, and lung was performed. MAIN RESULTS: Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in S(vO(2. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP. CONCLUSIONS: Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH

  2. Choroid plexus epithelial monolayers – a cell culture model from porcine brain

    Directory of Open Access Journals (Sweden)

    Reichel Valeska

    2006-12-01

    Full Text Available Abstract Background The goal of the present study was to develop an in vitro choroid plexus (CP epithelial cell culture model for studying transport of protein-mediated drug secretion from blood to cerebrospinal fluid (CSF and vice versa. Methods Cells were isolated by mechanical and enzymatic treatment of freshly isolated porcine plexus tissue. Epithelial cell monolayers were grown and CSF secretion and transepithelial resistance were determined. The expression of f-actin as well as the choroid plexus marker protein transthyretin (TTR, were assessed. The expression of the export proteins p-glycoprotein (Pgp, Abcb1 and multidrug resistance protein 1 (Mrp1, Abcc1 was studied by RT-PCR, Western-blot and immunofluorescence techniques and their functional activity was assessed by transport and uptake experiments. Results Choroid plexus epithelial cells were isolated in high purity and grown to form confluent monolayers. Filter-grown monolayers displayed transendothelial resistance (TEER values in the range of 100 to 150 Ωcm2. Morphologically, the cells showed the typical net work of f-actin and expressed TTR at a high rate. The cultured cells were able to secrete CSF at a rate of 48.2 ± 4.6 μl/cm2/h over 2–3 hours. The ABC-export protein Mrp1 was expressed in the basolateral (blood-facing membranes of cell monolayers and intact tissue. P-glycoprotein showed only low expression within the apical (CSF directed membrane but was located more in sub-apical cell compartments. This finding was paralleled by the lack of directed excretion of p-glycoprotein substrates, verapamil and rhodamine 123. Conclusion It was demonstrated that CP epithelium can be isolated and cultured, with cells growing into intact monolayers, fully differentiating and with properties resembling the tissue in vivo. Thus, the established primary porcine CP model, allowing investigation of complex transport processes, can be used as a reliable tool for analysis of xenobiotic

  3. Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia

    Institute of Scientific and Technical Information of China (English)

    LUO Jing-yun; WU Gui-fu; XIONG Yan; CHEN Guo-wei; XIE Qiang; YANG Da-ya; HE Xiao-hong; ZHANG Yan; LIU Dong-hong; WANG Kui-jian; MA Hong; ZHENG Zhen-sheng; DU Zhi-min

    2009-01-01

    Background Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris,but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34+, CD29+, and CD106+.Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n=6), hypercholesterolemic diet (CHOL, n=6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n=6), and hypercholesterolemJc diet with EECP treatment (EECP, n=6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1α (SDF-1α) in porcine myocardium were assessed, respectively.Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3±5.6) pg/ml at week 15 vs (26.2±3.7) pg/ml at week 12, P <0.05,and (46.9±6.1) pg/ml at week 18 vs (26.2±3.7) pg/ml at week 12, P <0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150±13.9) pg/ml at week 18 vs (24.8±5.4)pg/ml at week 12, P <0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108±13 vs 26±6 per 105 leukocytes, P <0.01), but not at week 18. The progenitor cell counts also increased significantly

  4. Validation of subject-specific cardiovascular system models from porcine measurements.

    Science.gov (United States)

    Revie, James A; Stevenson, David J; Chase, J Geoffrey; Hann, Christopher E; Lambermont, Bernard C; Ghuysen, Alexandre; Kolh, Philippe; Shaw, Geoffrey M; Heldmann, Stefan; Desaive, Thomas

    2013-02-01

    A previously validated mathematical model of the cardiovascular system (CVS) is made subject-specific using an iterative, proportional gain-based identification method. Prior works utilised a complete set of experimentally measured data that is not clinically typical or applicable. In this paper, parameters are identified using proportional gain-based control and a minimal, clinically available set of measurements. The new method makes use of several intermediary steps through identification of smaller compartmental models of CVS to reduce the number of parameters identified simultaneously and increase the convergence stability of the method. This new, clinically relevant, minimal measurement approach is validated using a porcine model of acute pulmonary embolism (APE). Trials were performed on five pigs, each inserted with three autologous blood clots of decreasing size over a period of four to five hours. All experiments were reviewed and approved by the Ethics Committee of the Medical Faculty at the University of Liege, Belgium. Continuous aortic and pulmonary artery pressures (P(ao), P(pa)) were measured along with left and right ventricle pressure and volume waveforms. Subject-specific CVS models were identified from global end diastolic volume (GEDV), stroke volume (SV), P(ao), and P(pa) measurements, with the mean volumes and maximum pressures of the left and right ventricles used to verify the accuracy of the fitted models. The inputs (GEDV, SV, P(ao), P(pa)) used in the identification process were matched by the CVS model to errors <0.5%. Prediction of the mean ventricular volumes and maximum ventricular pressures not used to fit the model compared experimental measurements to median absolute errors of 4.3% and 4.4%, which are equivalent to the measurement errors of currently used monitoring devices in the ICU (∼5-10%). These results validate the potential for implementing this approach in the intensive care unit. PMID:22126892

  5. Low-shear modelled microgravity environment maintains morphology and differentiated functionality of primary porcine hepatocyte cultures.

    Science.gov (United States)

    Nelson, Leonard J; Walker, Simon W; Hayes, Peter C; Plevris, John N

    2010-01-01

    Hepatocytes cultured in conventional static culture rapidly lose polarity and differentiated function. This could be explained by gravity-induced sedimentation, which prevents formation of complete three-dimensional (3D) cell-cell/cell-matrix interactions and disrupts integrin-mediated signals (including the most abundant hepatic integrin alpha(5)beta(1)), important for cellular polarity and differentiation. Cell culture in a low fluid shear modelled microgravity (about 10(-2) g) environment promotes spatial colocation/self-aggregation of dissociated cells and induction of 3D differentiated liver morphology. Previously, we demonstrated the utility of a NASA rotary bioreactor in maintaining key metabolic functions and 3D aggregate formation of high-density primary porcine hepatocyte cultures over 21 days. Using serum-free chemically defined medium, without confounding interactions of exogenous bioscaffolding or bioenhancing surface materials, we investigated features of hepatic cellular polarity and differentiated functionality, including expression of hepatic integrin alpha(5), as markers of functional morphology. We report here that in the absence of exogenous biomatrix scaffolding, hepatocytes cultured in serum-free chemically defined medium in a microgravity environment rapidly (microgravity environment may promote tissue-like self-organization of dissociated cells, and offer advantages over spheroids cultured in conventional formats to delineate optimal conditions for enhanced directed tissue self-assembly. PMID:20395654

  6. Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model.

    Science.gov (United States)

    Parker-Cote, Jennifer L; O'Rourke, Dorcas P; Brewer, Kori L; Lertpiriyapong, Kvin; Punja, Mohan; Bush, Sean P; Miller, Susan N; Meggs, William J

    2015-12-01

    Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites. PMID:25952763

  7. 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.

  8. A pilot study on ultrasound-assisted liposuction of the greater omentum in porcine models.

    Science.gov (United States)

    Sumiyama, Kazuki; Utsunomiya, Kazunori; Ohya, Tomohiko; Aihara, Hiroyuki; Ikeda, Keiichi; Imazu, Hiroo; Tamai, Naoto; Nagano, Hiroshi; Ishinoda, Yasuhiro; Tajiri, Hisao

    2012-03-01

    The greater omentum is the largest depot of visceral fat, and recent studies implicate removal of omental fat as a therapeutic option for metabolic syndrome (MS). This study evaluated the technical feasibility of reducing omental fat by using ultrasound-assisted liposuction (UAL) in porcine models. We removed as much omental adipose tissues as possible with a novel ultrasonic aspirator specifically designed for visceral liposuction that was inserted into the peritoneal cavity via the bilateral hypochondrial trocars. The greater part of the omental surface was emulsified and suctioned within 12.4 ± 9.2 (mean ± SD) min. In the survival study, all animals survived for two weeks without clinically evident complications following UAL. Histological examinations confirmed a substantial reduction in omental fat in pigs subjected to UAL. In conclusion, the pilot animal study conducted here demonstrated the technical feasibility of omental liposuction. UAL thus has potential as a relatively non-invasive liposuction approach to treat MS by selectively reducing the visceral fat content of the greater omentum. PMID:21395461

  9. 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%.

  10. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.

    Science.gov (United States)

    Potash, Andrea E; Wallen, Tanner J; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; Stoltz, David A; Zabner, Joseph; Chang, Eugene H

    2013-05-01

    Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis. PMID:23511247

  11. Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead

    Science.gov (United States)

    Weymann, Alexander; Patil, Nikhil Prakash; Sabashnikov, Anton; Jungebluth, Philipp; Korkmaz, Sevil; Li, Shiliang; Veres, Gabor; Soos, Pal; Ishtok, Roland; Chaimow, Nicole; Pätzold, Ines; Czerny, Natalie; Schies, Carsten; Schmack, Bastian; Popov, Aron-Frederik; Simon, André Rüdiger; Karck, Matthias; Szabo, Gabor

    2014-01-01

    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. PMID:25365554

  12. 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.

  13. Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study.

    Science.gov (United States)

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E

    2016-01-01

    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson's trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation

  14. Chronic bacterial infection models for BRM screening.

    Science.gov (United States)

    Dickneite, G; Schorlemmer, H U; Sedlacek, H H

    1984-05-01

    Models of chronic infections have been established to test the therapeutic and prophylactic potency of biological response modifiers (BRM). As an example for a BRM the immunostimulating drug Bestatin was tested. It is of dipeptide nature and was purified from culture supernatants of Streptomyces olivoreticuli. In two chronic bacterial infection models, induced by the inoculation of NRMI mice with Salmonella typhimurium or with a nephropathogenic strain of Escherichia coli, Bestatin acted prophylactically as well as therapeutically. This could be seen from the reduction of bacterial organ colonization and the inhibition of organ lesion formation. Bestatin could be shown to stimulate macrophage activity and to potentiate delayed type hypersensitivity, but not be effective on the humoral immune response. PMID:6383323

  15. 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.

  16. Laparoendoscopic single-site simple nephrectomy using a magnetic anchoring system in a porcine model

    Science.gov (United States)

    Choi, Young Hyo; Lee, Hye Won; Lee, Seo Yeon; Han, Deok Hyun; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong

    2016-01-01

    Purpose Magnetic anchoring devices may reduce the number of port sites needed in laparoscopic surgery. In this study, we prospectively assessed the feasibility of using a magnetic anchoring and guidance system (MAGS) in laparoendoscopic single-site (LESS) surgery performed by novices. Materials and Methods A total of 10 LESS simple nephrectomies were performed with or without MAGS in a nonsurvival porcine model by 6 operators with no previous LESS surgery experience. After installation of the homemade single port, an intra-abdominal magnet was fixed to the renal parenchyma with suturing and stabilized by an external magnet placed on the flank so that the position of the kidney could be easily changed by moving the external handheld magnet. The length of the procedure and any intraoperative complications were evaluated. Results Operative time (mean±standard deviation) was shorter in the group using the magnetic anchoring device (M-LESS-N) than in the group with conventional LESS nephrectomy (C-LESS-N) (63±20.8 minutes vs. 82±40.7 minutes, respectively). Although all nephrectomies were completed uneventfully in the M-LESS-N group, renal vein injury occurred during dissection of the renal hilum in two cases of C-LESS-N and was resolved by simultaneous transection of the renal artery and vein with an Endo-GIA stapler. Conclusions LESS-N using MAGS is a feasible technique for surgeons with no LESS surgery experience. Taking into account the 2 cases of renal vein injury in the C-LESS-N group, the application of MAGS may be beneficial for overcoming the learning curve of LESS surgery. PMID:27195320

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

    International Nuclear Information System (INIS)

    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

  18. 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.

  19. Experimental laparoscopic and thoracoscopic discectomy and instrumented spinal fusion. A feasibility study using a porcine model.

    Science.gov (United States)

    Mühlbauer, M; Ferguson, J; Losert, U; Koos, W T

    1998-03-01

    To explore the safety and the effectiveness of laparoscopic and thoracoscopic spinal surgery, an acute/non-survival animal trial was performed in 5 pigs using rigid and flexible endoscopes, flouroscopy, a holmium-YAG laser, and prototype instruments and implants. Our study aimed to approach the intervertebral disc space and spinal canal using laparoscopic and thoracoscopic techniques and to explore the potential and limits for endoscopic anterior spinal decompression and fusion. In a lateral recumbency access was provided to the anterolateral aspect of the lumbar spine from L1/2 to L7/S1, the thoracic spine was accessible from T2/3 to the diaphragmatic insertion. Complete disc space emptying with penetration into the spinal canal could be performed, epidural bleeding could be controlled by a hemostatic sponge, however bleeding restricted visualization for further endoscopic manipulation in the spinal canal. Intervertebral fusion was accomplished at T6/7, L4/5 and L7/S1 using small fragment plates with 3.5 mm screws and iliac bone grafts or prototype carbon fiber cages. On post mortem examination we found no dural tears and no nerve root damage, all animals had stabilized fusion sites and good implant position. We conclude that minimally invasive thoracoscopic and laparoscopic approaches to the spine are feasible and safe to perform disc decompression and implant placement for spinal fusion. In addition to currently performed laparoscopic interbody fusion, also plate fixation to reestablish lordosis of the lumbar spine is feasible at least in the porcine model. Careful disc decompression must be performed prior to implant introduction to prevent iatrogenic disc protrusion and spinal cord or nerve root compression. However, further surgical exploration of the spinal canal using these techniques does not provide adequate visualization of epidural spaces and therefore must be regarded as unsafe. PMID:9565956

  20. 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

    OpenAIRE

    N'Djin, W. Apoutou; Chapelon, Jean-Yves; Melodelima, David

    2015-01-01

    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 ...

  1. Graft Flow Unaffected by Full Occlusion of Left Anterior Descending Artery during Coronary Artery Bypass Grafting in a Porcine Model

    DEFF Research Database (Denmark)

    Torstensson, Gustav Nils Johannes; Torp, Thomas Lee; Rasuli-Oskuii, Nader;

    2013-01-01

    Background: We investigated in a porcine model whether measuring both the flow distal to an anastomosis and the graft transit time flow (TTF) gives a more accurate picture of the true blood flow in the left anterior descending artery (LAD) than graft TTF measurement alone.Methods: We performed off-pump...... anastomosis, despite a fully occluded LAD. This result suggests that graft TTF measurement alone is not sufficient when performing CABG, and measurement of flow distal to the anastomosis is also necessary to determine the true blood flow in the LAD....

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

    OpenAIRE

    Wang Shuo; Wu Jun-Yuan; Li Chun-Sheng

    2012-01-01

    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 fibrill...

  3. Gastric pH and motility in a porcine model of acute lung injury using a wireless motility capsule

    OpenAIRE

    Rauch, Stefan; Muellenbach, Ralf M.; Johannes, Amélie; Zollhöfer, Bernd; Roewer, Norbert

    2011-01-01

    Summary Background Evaluation of gastric pH and motility in a porcine model of acute lung injury using a novel, wireless motility capsule. Material/Methods A motility capsule was applied into the stomach of 7 Pietrain pigs with acute lung injury induced by high volume saline lavage. Wireless transmission of pH, pressure and temperature data was performed by a recorder attached to the animal’s abdomen. Gastric motility was evaluated using pH and pressure values, and capsule location was confir...

  4. 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...

  5. 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...... completed the trial. 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...

  6. 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

  7. IN VITRO STUDY ON THE STEROIDOGENIC EFFECT OF USED VEGETABLE OILS IN PORCINE MODEL

    OpenAIRE

    Adriana Kolesárová; Nora Maruniaková; Marek Halenár; Marína Medveďová; Shubhadeep Roychoudhury

    2013-01-01

    Vegetable oils are extracted from seeds like rapeseed, soybean, corn, sunflower, safflower and are found in majority of processed foods. A study was conducted in western Slovakia to determine possible effect of used vegetable oils (100 µl/ml) after cooking in households, school canteens and fast food restaurants on secretion activity of steroid hormones progesterone and 17 β-estradiol on porcine ovarian granulosa cells in vitro. Progesterone and estradiol are essential for normal ovarian cycl...

  8. 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

    2016-01-01

    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 (SecPBMC), apoptotic PBMCs (Apo-SecPBMC), or controls. The wounds treated with Apo-SecPBMC had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-SecPBMC had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-SecPBMC significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting. PMID:27125302

  9. Simultaneous irrigation and negative pressure wound therapy enhances wound healing and reduces wound bioburden in a porcine model.

    Science.gov (United States)

    Davis, Kathryn; Bills, Jessica; Barker, Jenny; Kim, Paul; Lavery, Lawrence

    2013-01-01

    Infected foot wounds are one of the most common reasons for hospitalization and amputation among persons with diabetes. The objective of the study was to investigate a new wound therapy system that employs negative pressure wound therapy (NPWT) with simultaneous irrigation therapy. For this study, we used a porcine model with full-thickness excisional wounds, inoculated with Pseudomonas aeruginosa. Wounds were treated for 21 days of therapy with either NPWT, NPWT with simultaneous irrigation therapy using normal saline or polyhexanide biguanide (PHMB) at low or high flow rates, or control. Data show that NPWT with either irrigation condition improved wound healing rates over control-treated wounds, yet did not differ from NPWT alone. NPWT improved bioburden over control-treated wounds. NPWT with simultaneous irrigation further reduced bioburden over control and NPWT-treated wounds; however, flow rate did not affect these outcomes. Together, these data show that NPWT with simultaneous irrigation therapy with either normal saline or PHMB has a positive effect on bioburden in a porcine model, which may translate clinically to improved wound healing outcomes. PMID:24134060

  10. Even Four Minutes of Poor Quality of CPR Compromises Outcome in a Porcine Model of Prolonged Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Heng Li

    2013-01-01

    Full Text Available Objective. Untrained bystanders usually delivered suboptimal chest compression to victims who suffered from cardiac arrest in out-of-hospital settings. We therefore investigated the hemodynamics and resuscitation outcome of initial suboptimal quality of chest compressions compared to the optimal ones in a porcine model of cardiac arrest. Methods. Fourteen Yorkshire pigs weighted 30 ± 2 kg were randomized into good and poor cardiopulmonary resuscitation (CPR groups. Ventricular fibrillation was electrically induced and untreated for 6 mins. In good CPR group, animals received high quality manual chest compressions according to the Guidelines (25% of animal’s anterior-posterior thoracic diameter during first two minutes of CPR compared with poor (70% of the optimal depth compressions. After that, a 120-J biphasic shock was delivered. If the animal did not acquire return of spontaneous circulation, another 2 mins of CPR and shock followed. Four minutes later, both groups received optimal CPR until total 10 mins of CPR has been finished. Results. All seven animals in good CPR group were resuscitated compared with only two in poor CPR group (P<0.05. The delayed optimal compressions which followed 4 mins of suboptimal compressions failed to increase the lower coronary perfusion pressure of five non-survival animals in poor CPR group. Conclusions. In a porcine model of prolonged cardiac arrest, even four minutes of initial poor quality of CPR compromises the hemodynamics and survival outcome.

  11. 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

    2016-01-01

    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. PMID:27125302

  12. 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

  13. Vesicoureteral reflux in young children: a study of radiometric thermometry as detection modality using an ex vivo porcine model

    Science.gov (United States)

    Jacobsen, Svein; Klemetsen, Øystein; Birkelund, Yngve

    2012-09-01

    Microwave radiometry is evaluated for renal thermometry tailored to detect the pediatric condition of vesicoureteral urine reflux (VUR) from the bladder through the ureter into the kidney. Prior to a potential reflux event, the urine is heated within the bladder by an external body contacting a hyperthermia applicator to generate a fluidic contrast temperature relative to normal body temperature. A single band, miniaturized radiometer (operating at 3.5 GHz) is connected to an electromagnetic-interference-shielded and suction-coupled elliptical antenna to receive thermal radiation from an ex vivo porcine phantom model. Brightness (radiometric) and fiberoptic temperature data are recorded for varying urine phantom reflux volumes (20-40 mL) and contrast temperatures ranging from 2 to 10 °C within the kidney phantom. The kidney phantom itself is located at 40 mm depth (skin-to-kidney center distance) and surrounded by the porcine phantom. Radiometric step responses to injection of urine simulant by a syringe are shown to be highly correlated with in situ kidney temperatures measured by fiberoptic probes. Statistically, the performance of the VUR detecting scheme is evaluated by error probabilities of making a wrong decision. Laboratory testing of the radiometric system supports the feasibility of passive non-invasive kidney thermometry for the detection of VUR classified within the two highest grades

  14. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    Science.gov (United States)

    Hornblower, V. D. M.; Yu, E.; Fenster, A.; Battista, J. J.; Malthaner, R. A.

    2007-01-01

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo.

  15. Vesicoureteral reflux in young children: a study of radiometric thermometry as detection modality using an ex vivo porcine model

    International Nuclear Information System (INIS)

    Microwave radiometry is evaluated for renal thermometry tailored to detect the pediatric condition of vesicoureteral urine reflux (VUR) from the bladder through the ureter into the kidney. Prior to a potential reflux event, the urine is heated within the bladder by an external body contacting a hyperthermia applicator to generate a fluidic contrast temperature relative to normal body temperature. A single band, miniaturized radiometer (operating at 3.5 GHz) is connected to an electromagnetic-interference-shielded and suction-coupled elliptical antenna to receive thermal radiation from an ex vivo porcine phantom model. Brightness (radiometric) and fiberoptic temperature data are recorded for varying urine phantom reflux volumes (20–40 mL) and contrast temperatures ranging from 2 to 10 °C within the kidney phantom. The kidney phantom itself is located at 40 mm depth (skin-to-kidney center distance) and surrounded by the porcine phantom. Radiometric step responses to injection of urine simulant by a syringe are shown to be highly correlated with in situ kidney temperatures measured by fiberoptic probes. Statistically, the performance of the VUR detecting scheme is evaluated by error probabilities of making a wrong decision. Laboratory testing of the radiometric system supports the feasibility of passive non-invasive kidney thermometry for the detection of VUR classified within the two highest grades (paper)

  16. 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

  17. Dysregulation of IFNα and IL-10 in central nervous systém in transgenic porcine Huntington´s disease model

    Czech Academy of Sciences Publication Activity Database

    Jarkovská, Karla; Valeková, Ivona; Kotrčová, Eva; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    Lisabon : Bioscope, 2015. s. 1-1. [International Conference on Analytical Proteomics /4./. 04.09.2015-07.09.2015, Lisabon] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : porcine Huntington´s disease model * multiplexing * cerebrospinal fluid Subject RIV: EB - Genetics ; Molecular Biology

  18. 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......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......, blood samples, and hemodynamic and histological analyses. As controls, 5 pigs underwent surgery involving only LAD artery ligation without CVBG. CVBG with LAD ligation was performed in 16 pigs; 12 survived CVBG and were monitored for 2-2.5 hours while in sinus rhythm, a 75% salvage rate after an...

  19. 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 in...... HO-1 mRNA was observed in small recipients than in donors and size-matched recipients indicating cortical injury. Improvement in early graft perfusion may be a goal to improve short- and long-term GFR and avoid graft thrombosis in pediatric recipients....

  20. Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model

    Institute of Scientific and Technical Information of China (English)

    Katsumi Kobayashi; Koshi Matsurnoto; Izumi Takeyoshi; Kiyohiro Oshima; Masato Muraoka; Takahiko Akao; Osamu Totsuka; Hisashi Shimizu; Hiroaki Sato; Kazumi Tanaka; Kenjiro Konno

    2007-01-01

    AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model.METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood flow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study.Those results were compared between the two groups.RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 < 0.05,120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004< 0.01). No significant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant.A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.611 < 0.05).Histological tissue damage was milder in the ANP group than in the control group.CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.

  1. Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation

    International Nuclear Information System (INIS)

    A porcine skin model was developed to characterize the dose-dependent response to high-dose radiation. The dorsal skin of a mini pig was divided into four paraspinal sections, with 11 small irradiation fields (2 cm × 2 cm) in each section, and a single fraction of 15, 30, 50 or 75 Gy was delivered to each section using a 6 MeV electron beam. A spectrophotometer measured gross skin changes, and a biopsy for each radiation dose was performed in the 1st, 2nd, 4th, 6th and 9th weeks for histology, immunostaining with anti-CD31, and western blotting with IL-6 and TGF-β1 to determine the degree of skin damage. After a 4-week latency period, erythema and dry desquamation, moist desquamation, and ulceration appeared at 4, 6 and 9 weeks, respectively. Gross skin toxicity was more pronounced, occurred early and continued to progress with irradiation >50 Gy, whereas complete healing was observed 12 weeks after 15 Gy. Spectrophotometry showed erythema indices rapidly increased during the first 4 weeks after irradiation. The number of eosinophils began rising sharply at 4 weeks and normalized after reaching peaks at 7-8 weeks. Microvessel density showed a biphasic pattern with a transient peak at 1 week, a nadir at 4-6 weeks, and maximum recovery at 9 weeks. Increase in the levels of IL-6 and TGF-β1 was detected soon after irradiation. Most of these parameters indicated complete healing of the skin 12 weeks after 15 Gy. Our porcine skin model provides an effective platform for studying high-dose radiation-induced skin injury, in particular histologic and molecular changes, during the early latency period. (author)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Animal models for investigating chronic pancreatitis

    OpenAIRE

    Aghdassi Alexander A; Mayerle Julia; Christochowitz Sandra; Weiss Frank U; Sendler Matthias; Lerch Markus M

    2011-01-01

    Abstract Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in t...

  5. Chronic pain: Model of psychosomatic disorder (review

    Directory of Open Access Journals (Sweden)

    Chernus N.P.

    2011-12-01

    Full Text Available The article presents a detailed review on epidemiology, pathogenesis and interrelation of serotonin neuromedia-tor metabolism in the central nervous system in state of chronic pain and depression. It has been demonstrated that neurophysiological conditions serve as psychological defense of an individual. That mechanism has been proved to «transform» serious emotions onto the inner level (body and it assists in the development of psychosomatic disorders — chronic pain syndrome

  6. Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome

    OpenAIRE

    Henderson, William R.; Barnbrook, Julian; Dominelli, Paolo B.; Griesdale, Donald EG; Arndt, Tara; Molgat-Seon, Yannick; Foster, Glen; Ackland, Gareth L; Xu, James; Ayas, Najib T.; Sheel, Andrew W.

    2014-01-01

    Background The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). Methods The present study was performed at the Centre for Comparative Medicine, ...

  7. Reduction of IFNα and IL-10 in central nervous system and increase in peripheral IL-8 in transgenic porcine Huntington´s disease model

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Valeková, Ivona; Jarkovská, Karla; Kotrčová, Eva; Motlík, Jan; Gadher, S. J.

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 10-11. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : porcine Huntington´s disease model * IFNα * IL-10 Subject RIV: EB - Genetics ; Molecular Biology

  8. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    Science.gov (United States)

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H.S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for harvest of EPC in human cell therapy studies. In addition the therapeutic effects of paracrine factors secreted by these cells was evaluated in vitro and in vivo. Intracoronary injection of autologous porcine EPC was associated with increased infarct territory mass and improved regional ventricular systolic function at 2 months compared to control. Treatment with conditioned media derived from autologous EPC was associated with similar improved effects on infarct territory mass and function. Histologic analysis of the infarct territory revealed significantly increased cardiomyocyte size in EPC and conditioned media treated groups, when compared to controls. A paracrine EPC effect was also verified in a pure myocardial preparation in which cardiomyocytes devoid of fibroblast, neuronal and vascular elements directly responded by increasing cell mass when exposed to the same conditioned media. Analysis of conditioned media revealed elevated levels of TGFβ1 (human 267.3±11.8 pg/ml, porcine 57.1±6.1 pg/ml), a recognized mediator of hypertrophic signaling in the heart. Neutralizing antibodies to TGFβ1 attenuated the pro-hypertrophic effect of conditioned media, and use of recombinant TGFβ1 added to fresh media replicated the pro-hypertrophic effects of conditioned media in vitro. These data demonstrate the potential of paracrine factors secreted from endothelial progenitor cells to induce cardiomyocyte hypertrophy contributing to increased infarct territory LV mass, with

  9. Porcine retrovirus: hybridization studies

    International Nuclear Information System (INIS)

    Tritium-labeled porcine retrovirus (PoRV) was isolated and purified, and kinetics of hybridization of this RNA with DNA from various sources was determined. Results indicate that PoRV is an endogenous porcine virus

  10. 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...... 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...... associated with obesity 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...

  11. 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 the...... 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...... 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...

  12. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program

    Science.gov (United States)

    Sequeira, Sonia; Chavez, Amy Holmes

    2016-01-01

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs. PMID:27032986

  13. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program.

    Science.gov (United States)

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-01-01

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs. PMID:27032986

  14. The Effects of Negative Pressure by External Tissue Expansion Device on Epithelial Cell Proliferation, Neo-Vascularization and Hair Growth in a Porcine Model

    OpenAIRE

    Hsiao, Hui-Yi; Liu, Jia-Wei; Brey, Eric M; Cheng, Ming-Huei

    2016-01-01

    While pre-treating a fat transplant recipient site with negative pressure has shown promise for increasing the fat survival rate, the underlying mechanisms have not been investigated, partly due to challenges related to immobilization of vacuum domes on large animal subjects. The aim of this study was to examine the effect of negative pressure treatment by External Tissue Expansion Device (ETED) on fat grating recipient sites in a porcine model. The ETED was designed to provide negative press...

  15. Evaluation of feasibility, efficiency and safety of a pure NOTES gastrojejunal bypass with gastric outlet obstruction, in an in vivo porcine model

    OpenAIRE

    Gonzalez, J.-M.; Bonin, E. A.; Vanbiervliet, G; Garnier, E.; Berdah, S.; K. Matthes; Barthet, M

    2013-01-01

    Introduction: Natural orifice transluminal endoscopic surgery (NOTES) gastrojejunal anastomosis (GJA) is a less invasive surgery for bariatric procedures and gastric outlet obstruction. The aim of this study was to evaluate the feasibility, efficacy, and safety of a pure NOTES gastrojejunal bypass using an in vivo porcine model. Material and methods: A prospective study was performed on nine swine. A double-channel scope was used. The intervention steps were: (i) gastric incision; (ii) perito...

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

    OpenAIRE

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

    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 ove...

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

    OpenAIRE

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

    2015-01-01

    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 cardiop...

  18. Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes

    Science.gov (United States)

    Cain, Clarence P.; Polhamus, Garrett D.; Roach, William P.; Stolarski, David J.; Schuster, Kurt J.; Stockton, Kevin; Rockwell, Benjamin A.; Chen, Bo; Welch, Ashley J.

    2006-07-01

    With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 µs) at 24-h postexposure are measured to be 99 and 83 Jcm-2 for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 Jcm-2 for a 5-mm-diam top-hat laser pulse.

  19. Is intervertebral disc pressure linked to herniation?: An in-vitro study using a porcine model.

    Science.gov (United States)

    Noguchi, Mamiko; Gooyers, Chad E; Karakolis, Thomas; Noguchi, Kimihiro; Callaghan, Jack P

    2016-06-14

    Approximately 40% of low back pain cases have been attributed to internal disc disruption. This disruption mechanism may be linked to intradiscal pressure changes, since mechanical loading directly affects the pressure and the stresses that the inner annulus fibrosus experiences. The objective of this study was to characterize cycle-varying changes in four dependent measures (intradiscal pressure, flexion-extension moments, specimen height loss, and specimen rotation angle) using a cyclic flexion-extension (CFE) loading protocol known to induce internal disc disruption. A novel bore-screw pressure sensor system was used to instrument 14 porcine functional spinal units. The CFE loading protocol consisted of 3600 cycles of flexion-extension range of motion (average 18.30 (SD 3.76) degrees) at 1Hz with 1500N of compressive load. On average, intradiscal pressure and specimen height decreased by 47% and 62%, respectively, and peak moments increased by 102%. From 900 to 2100 cycles, all variables exhibited significant changes between successive time points, except for the specimen posture at maximum pressure, which demonstrated a significant shift towards flexion limit after 2700 cycles. There were no further changes in pressure range after 2100 cycles, whereas peak moments and height loss were significantly different from prior time points throughout the CFE protocol. Twelve of the 14 specimens showed partial herniation; however, injury type was not significantly correlated to any of the dependent measures. Although change in pressure was not predictive of damage type, the increase in pressure range seen during this protocol supports the premise that repetitive combined loading (i.e., radial compression, tension and shear) imposes damage to the inner annulus fibrosus, and its failure mechanism may be linked to fatigue. PMID:27157242

  20. A Model of Chronic Nutrient Infusion in the Rat

    OpenAIRE

    Fergusson, Grace; Ethier, Mélanie; Zarrouki, Bader; Fontés, Ghislaine; Poitout, Vincent

    2013-01-01

    Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of cathete...

  1. Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

    Directory of Open Access Journals (Sweden)

    Leonardo de Albuquerque dos Santos Abreu

    2011-10-01

    Full Text Available PURPOSE: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R injury. MATERIALS AND METHODS: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr and plasma iohexol clearance (CLioh were measured before surgery and on postoperative days (PODs 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant. RESULTS: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively. Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups. CONCLUSION: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model.

    Science.gov (United States)

    Lim, Kyung Seob; Park, Jun-Kyu; Jeong, Myung Ho; Bae, In-Ho; Nah, Jae-Woon; Park, Dae Sung; Kim, Jong Min; Kim, Jung Ha; Lee, So Youn; Jang, Eun Jae; Jang, Suyoung; Kim, Hyun Kuk; Sim, Doo Sun; Park, Keun-Ho; Hong, Young Joon; Ahn, Youngkeun; Kang, Jung Chaee

    2016-04-01

    The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78 % in BMS vs. 51.5 ± 12.20 % in AES vs. 34.7 ± 7.23 % in SES vs. 28.7 ± 7.30 % in SAS, P coating to suppress neointimal hyperplasia. PMID:26886814

  4. 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.

  5. 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.

  6. Predictive validity of behavioural animal models for chronic pain

    OpenAIRE

    Berge, Odd-Geir

    2011-01-01

    Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between precl...

  7. 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.

  8. Combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction in a porcine model of cardiac arrest.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group, which received central venous injection of either epinephrine combined with esmolol (EE group, epinephrine (EP group, or saline (SA group. Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC. Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output (P<0.05, and improved oxygen metabolism (oxygen delivery and oxygen consumption (P<0.05, which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium. CONCLUSIONS: Esmolol, a short-acting β₁-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.

  9. 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.)

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

    Directory of Open Access Journals (Sweden)

    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

  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. PMID:25025701

  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

    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. Models for Reactive and Chronic Depression in Infancy.

    Science.gov (United States)

    Field, Tiffany

    1986-01-01

    Presents studies on primates and human infants suggesting that maternal depression may predispose the infant to chronic depression. Findings also suggest that the effect of early separations from the mother may provide a model for reactive depression in the infant. (Author/BB)

  14. Modelling and simulating the dynamics of in-stent restenosis in porcine coronary arteries

    OpenAIRE

    Tahir, H.

    2013-01-01

    The results highlighted in this thesis show the importance of iterative model development in parallel with analysis and interpretation of biological data. It is clear that the mathematical models presented in this thesis that were used to model the process of in-stent restenosis (ISR) have been able to point to key aspects in the response for which little experimental data exists. Considering the initial response; does ISR initially start due to damage of the intima which activates the medial...

  15. Cost of post-weaning multi-systemic wasting syndrome and porcine circovirus type-2 subclinical infection in England – An economic disease model

    OpenAIRE

    Alarcon, Pablo; Rushton, Jonathan; Wieland, Barbara

    2013-01-01

    Post-weaning multi-systemic wasting syndrome (PMWS) is a multi-factorial disease with major economic implications for the pig industry worldwide. The present study aimed to assess the economic impact of PMWS and porcine circovirus type 2 (PCV2) subclinical infections (PCV2SI) for farrow-to-finish farms and to estimate the resulting cost to the English pig industry. A disease model was built to simulate the varying proportions of pigs in a batch that get infected with PCV2 and develop either P...

  16. Sonic hedgehog expression in a rat model of chronic pancreatitis

    Science.gov (United States)

    Wang, Luo-Wei; Lin, Han; Lu, Yi; Xia, Wei; Gao, Jun; Li, Zhao-Shen

    2014-01-01

    AIM: To analyze the activation of sonic hedgehog (SHh) signaling pathways in a rat model of chronic pancreatitis. METHODS: Forty Wistar rats were randomly divided into 2 groups: experimental group and control group (20 rats in each group). Dibutyltin dichloride was infused into the tail vein of the rats to induce chronic pancreatitis in the experimental group. The same volume of ethanol and glycerol mixture was infused in the control group. The expression of Ptch, Smo and Gli were analyzed using immunohistochemistry, and real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the control group, significant histological changes in terms of the areas of abnormal architecture, glandular atrophy, fibrosis, pseudo tubular complexes, and edema were observed at week 4 in the experimental group. The expression of Ptch1, Smo and Gli1 in the pancreatic tissue increased significantly in the experimental group. Using RT-PCR, mRNA levels of Ptch, Smo and Gli in the experimental group increased significantly compared with the control group. CONCLUSION: The SHh signaling pathway is aberrantly activated in rats with chronic pancreatitis. The SHh signaling pathway plays an important role in the development of chronic pancreatitis. These results may be helpful in studies focusing on the relationship between chronic pancreatitis and pancreatic cancer. PMID:24782623

  17. Evaluation of inflammatory cytokines and chemokines in porcine model of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Valeková, Ivona; Kupcová Skalníková, Helena; Klíma, Jiří; Juhás, Štefan; Motlík, Jan

    Mělník : IAPG, 2013. [Large Animal Models of Neurodegenerative Diseases /2./. 17.11.2013-19.11.2013, Liblice] Institutional support: RVO:67985904 Keywords : Huntington ´s Disease Subject RIV: FH - Neurology

  18. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

    Institute of Scientific and Technical Information of China (English)

    Yi Gao; Ning Mu; Xiao-Ping Xu; Yan Wang

    2005-01-01

    .CONCLUSION: The porcine ALF model established bytwo-phase devascularized surgery is valid and reproducible.The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.

  19. 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...... frequent complication was a neurological deficit in the lower limbs. ConclusionIn 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, it’s also a potential...

  20. 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...... 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...

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

    Directory of Open Access Journals (Sweden)

    Brian O. Kloster

    2015-03-01

    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, it's also a potential model for further studies of novel endovascular devices and their complications.

  2. Acute porcine model of huntington´s disease- a candidate for pre-clinical tests

    Czech Academy of Sciences Publication Activity Database

    Hruška-Plocháň, Marian; Juhás, Štefan; Juhásová, Jana; Galik, J.; Miyanohara, A.; Maršala, M.; Bjarkam, C. R.; Cattaneo, E.; Difiglia, M.

    Amsterdam : European Neuroscience Society, 2010. s. 109-109. [FENS Forum of European Neuroscience /7./. 03.07.2010-07.07.2010, Amsterdam] Institutional research plan: CEZ:AV0Z50450515 Keywords : Huntington ´s disease * Animal model * Neurodegeneration Subject RIV: FH - Neurology

  3. 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.

  4. Generating a Natural Porcine Model of Gastrointestinal Food Allergy to Peanut

    Science.gov (United States)

    The peanut (Arachis hypogaea) is an extremely potent allergen and is one of the most life-threatening food sensitivities known. Peanuts cause the majority of food-related anaphylaxis in children, adolescents, and adults. There is no good animal model currently in place to study peanut allergies. Exp...

  5. Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical model

    NARCIS (Netherlands)

    Schachtschneider, K.M.; Madsen, O.; Park, C.; Rund, L.A.; Groenen, M.A.M.; Schook, L.B.

    2015-01-01

    Background: Pigs (Sus scrofa) provide relevant biomedical models to dissect complex diseases due to their anatomical, genetic, and physiological similarities with humans. Aberrant DNA methylation has been linked to many of these diseases and is associated with gene expression; however, the functiona

  6. Cell-mediated anti-tumour immunity induced by devitalization in porcine malignant melanoma model

    Czech Academy of Sciences Publication Activity Database

    Horák, Vratislav; Soukupová, Pavla; Šinkora, J.; Řeháková, Z.; Málek, Ondřej; Hradecký, Jan; Klaudy, Jiří

    Praha: European School of Hematology, 2003. s. 1. [Euroconference on Animal Models of Human Diseases/3./. 16.05.2003-18.05.2003, Praha] R&D Projects: GA ČR GA524/01/0162; GA AV ČR IBS5045113 Institutional research plan: CEZ:AV0Z5045916 Keywords : devitalization Subject RIV: ED - Physiology

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

    Science.gov (United States)

    Egloff, Niklaus; Hirschi, Anna; von Känel, Roland

    2013-01-01

    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. PMID:24231792

  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. PMID:21741703

  9. Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

    Science.gov (United States)

    Wehman, Brody; Sharma, Sudhish; Pietris, Nicholas; Mishra, Rachana; Siddiqui, Osama T; Bigham, Grace; Li, Tieluo; Aiello, Emily; Murthi, Sarah; Pittenger, Mark; Griffith, Bartley; Kaushal, Sunjay

    2016-06-01

    Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P lesions. PMID:27106046

  10. Vasopressin improves survival in a porcine model of abdominal vascular injury

    OpenAIRE

    Stadlbauer, Karl H; Wagner-Berger, Horst G; Krismer, Anette C; Voelckel, Wolfgang G; Konigsrainer, Alfred; Lindner, Karl H; Wenzel, Volker

    2007-01-01

    Introduction We sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs. Methods During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rat...

  11. In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

    International Nuclear Information System (INIS)

    To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularity of the single-antenna ablation zones measured 0.64 ± 0.12, with a diameter of 35.7 ± 8.7 mm along the axis of the antenna and 32.7 ± 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 ± 7.7 along the axis of the antenna and 54.8 ± 8.5 mm perpendicular to the feeding point; circularity was 0.70 ± 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of ≤4 cm with no heat sink effect from vessels of ≤6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.

  12. Low-Shear Modelled Microgravity Environment Maintains Morphology and Differentiated Functionality of Primary Porcine Hepatocyte Cultures

    OpenAIRE

    Nelson, Leonard J; Walker, Simon W.; Peter C. Hayes; Plevris, John N

    2010-01-01

    Hepatocytes cultured in conventional static culture rapidly lose polarity and differentiated function. This could be explained by gravity-induced sedimentation, which prevents formation of complete three-dimensional (3D) cell-cell/cellmatrix interactions and disrupts integrin-mediated signals (including the most abundant hepatic integrin alpha(5)beta(1)), important for cellular polarity and differentiation. Cell culture in a low fluid shear modelled microgravity (about 10(-2) g) environment p...

  13. Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model

    OpenAIRE

    Jacquet-Lagrèze, Matthias; Allaouchiche, Bernard; Restagno, Damien; Paquet, Christian; Ayoub, Jean-Yves; Etienne, Jêrome; Vandenesch, François; Dauwalder, Olivier; Bonnet, Jeanne-Marie; Junot, Stéphane

    2015-01-01

    Introduction Esmolol may efficiently reduce heart rate (HR) and decrease mortality during septic shock. An improvement of microcirculation dissociated from its macrocirculatory effect may a role. The present study investigated the effect of esmolol on gut and sublingual microcirculation in a resuscitated piglet model of septic shock. Methods Fourteen piglets, anesthetized and mechanically ventilated, received a suspension of live Pseudomonas aeruginosa. They were randomly assigned to two grou...

  14. 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 < 0.7), and we found that flow

  15. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model

    OpenAIRE

    Wang, Jian; ZHOU, DA-QING; He, Meng; Li, Wen-Gang; PANG, XIANG; YU, XIAO-XIANG; Jiang, Bo

    2013-01-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as cont...

  16. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model.

    Science.gov (United States)

    Wang, Jian; Zhou, DA-Qing; He, Meng; Li, Wen-Gang; Pang, Xiang; Yu, Xiao-Xiang; Jiang, Bo

    2013-05-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  17. 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.

  18. The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

    DEFF Research Database (Denmark)

    Stenbøg, Elisabeth Vidstid; Steinbruchel, Daniel Andreas; Thomsen, Anne Bloch;

    2001-01-01

    models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls...... included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow....... By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These...

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

    International Nuclear Information System (INIS)

    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 R2 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

    Science.gov (United States)

    Sánchez-Margallo, F. M.; Latorre, R.; López-Albors, O.; Wise, R.; Malbrain, M. L. N. G.; Castellanos, G.

    2016-01-01

    Introduction 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. Materials and Methods 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. Results 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. Conclusion 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. PMID

  1. 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.)

  2. Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

    OpenAIRE

    Zoe eFonseca-Kelly; Mayssa eNassrallah; Jorge eUribe; Khan, Reas S.; Kimberly eDine; Mahasweta eDutt; Shindler, Kenneth S.

    2012-01-01

    Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current st...

  3. Establishing a cat model of chronic optic nerve compression injury

    Institute of Scientific and Technical Information of China (English)

    Feng Yu; Shaoji Yuan; Rongwei Zhang; Yicheng Lu; Meiqing Lou

    2009-01-01

    BACKGROUND:An animal model of chronic optic nerve injury is necessary to further understand the pathological mechanisms involved.OBJECTIVE:To establish a stabilized,chronic,optic nerve crush model,which is similar to the clinical situation to explore histopathological and optic electrophysiological changes involved in this injury.DESIGN,TIME AND SETTING:A randomized and controlled animal trial was performed at Shanghai Institute of Neurosurgery from May to October 2004.MATERIALS:A BAL3XRAY undetachable balloon and Magic-BD catheter were provided by BLAT,France;JX-2000 biological signal processing system by Second Military Medical University of Chinese PLA,China;inverted phase contrast microscopy by Olympus,Japan.METHODS:A total of twenty normal adult cats were randomly assigned to control (n = 5) and model (n = 15) groups,according to different doses of contrast agent injected through balloons as follows:0.2 mL injection,0.25 mL injection,and 0.35 mL injection,with each group containing 5 animals.Imitating the clinical pterion approach,the optic nerves were exposed using micro-surgical methods.An engorged undetachable balloon was implanted beneath the nerve and connected to a catheter.Balloon size was controlled with a contrast agent injection (0.1 mL/10 min) to form an occupying lesion model similar to sellar tumors.MAIN OUTCOME MEASURES:The visually evoked potential examination was used to study optical electrophysiology changes in pre-post chronic optical nerve injury.Ultrastructural pathological changes to the optic nerve were analyzed by electron microscopy.RESULTS:During the early period (day 11 after modeling),visually evoked potential demonstrated no significant changes.In the late period (day 51 after modeling),recorded VEP demonstrated that P1 wave latency was prolonged and P1 wave amplitude was obviously reduced.Following injury,the endoneurium,myelin sheath,lamella,axolemma,and axon appeared disordered.CONCLUSION:Results demonstrated that the chronic

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

    Science.gov (United States)

    Barington, Kristiane; Jensen, Henrik Elvang

    2016-05-01

    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 kept in anesthesia for 2, 4, 6 or 8 h, after which they were euthanized, and skin and muscle tissues were sampled for histology. As control, two pigs were included. The gross appearance of bruises developed similarly until 0.5 h after infliction at which time the visibility of the bruises depended on the force. The infiltration of subcutaneous neutrophils depended on the time and force used which was confirmed by both manual evaluation and image analysis of immunostained skin sections. In the muscle tissue, the number of macrophages was found useful for age determination in bruises inflicted 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. PMID:27085141

  5. 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

  6. Attitudes of Doctors and Nurses toward the Chronic Care Model

    Directory of Open Access Journals (Sweden)

    Rolando Bonal Ruiz

    2015-06-01

    Full Text Available Background: the fact that chronic diseases replace traditional causes of morbidity and mortality in a country, or are on a par with major common health problems, demands the development of new strategies to address them. Objective: to explore attitudes of doctors and nurses from the Rolando López Peña Polyclinic toward the Chronic Care Model. Methods: a quantitative and qualitative cross-sectional study was conducted including the 22 family physicians and 26 nurses who provide care to patients with chronic diseases and were at the polyclinic at the time of the study. All were administered a 5 point Likert scale and a focus group interview, which was taped, transcribed and analyzed. Results: the attitudinal results correspond with the actions assessed in each component of the model, being the most common barriers: the lack of awareness and training on the new approaches to care of these patients, work overload created by other programs such as the maternal-child and vector control programs, uncertainties on the effectiveness of patient education and ignorance of the practice guidelines. Conclusions: favorable attitudes toward the introduction of the model to the practice of the family physician and nurse predominated as long as organizational changes are made and the suggestions of these service providers are put into practice with the support of the decision makers of the health sector.

  7. Mathematical model of gas plasma applied to chronic wounds

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J. G.; Liu, X. Y.; Liu, D. W.; Lu, X. P. [State Key Lab of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, WuHan, HuBei 430074 (China); Zhang, Y. T. [Shandong Provincial Key Lab of UHV Technology and Gas Discharge Physics, School of Electrical Engineering, Shandong University, Jinan, Shandong Province 250061 (China)

    2013-11-15

    Chronic wounds are a major burden for worldwide health care systems, and patients suffer pain and discomfort from this type of wound. Recently gas plasmas have been shown to safely speed chronic wounds healing. In this paper, we develop a deterministic mathematical model formulated by eight-species reaction-diffusion equations, and use it to analyze the plasma treatment process. The model follows spatial and temporal concentration within the wound of oxygen, chemoattractants, capillary sprouts, blood vessels, fibroblasts, extracellular matrix material, nitric oxide (NO), and inflammatory cell. Two effects of plasma, increasing NO concentration and reducing bacteria load, are considered in this model. The plasma treatment decreases the complete healing time from 25 days (normal wound healing) to 17 days, and the contributions of increasing NO concentration and reducing bacteria load are about 1/4 and 3/4, respectively. Increasing plasma treatment frequency from twice to three times per day accelerates healing process. Finally, the response of chronic wounds of different etiologies to treatment with gas plasmas is analyzed.

  8. Biomechanical investigation of impact induced rib fractures of a porcine infant surrogate model.

    Science.gov (United States)

    Blackburne, William B; Waddell, J Neil; Swain, Michael V; Alves de Sousa, Ricardo J; Kieser, Jules A

    2016-09-01

    This study investigated the structural, biomechanical and fractographic features of rib fractures in a piglet model, to test the hypothesis that fist impact, apart from thoracic squeezing, may result in lateral costal fractures as observed in abused infants. A mechanical fist with an accelerometer was constructed and fixed to a custom jig. Twenty stillborn piglets in the supine position were impacted on the thoracic cage. The resultant force versus time curves from the accelerometer data showed a number of steps indicative of rib fracture. The correlation between impact force and number of fractures was statistically significant (Pearson׳s r=0.528). Of the fractures visualized, 15 completely pierced the parietal pleura of the thoracic wall, and 5 had butterfly fracture patterning. Scanning electron microscopy showed complete bone fractures, at the zone of impact, were normal to the axis of the ribs. Incomplete vertical fractures, with bifurcation, occurred on the periphery of the contact zone. This work suggests the mechanism of rib failure during a fist impact is typical of the transverse fracture pattern in the anterolateral region associated with cases of non-accidental rib injury. The impact events investigated have a velocity of ~2-3m/s, approximately 2×10(4) times faster than previous quasi-static axial and bending tests. While squeezing the infantile may induce buckle fractures in the anterior as well as posterior region of the highly flexible bones, a fist punch impact event may result in anterolateral transverse fractures. Hence, these findings suggest that the presence of anterolateral rib fractures may result from impact rather than manual compression. PMID:27310573

  9. 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

  10. 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.

  11. 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; Agerholm, Jørgen S.

    2015-01-01

    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...... 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......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...

  12. 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

  13. 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.

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

    OpenAIRE

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

    2013-01-01

    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 wer...

  15. Mortality model based on delays in progression of chronic diseases: alternative to cause elimination model.

    OpenAIRE

    Manton, K G; Patrick, C H; Stallard, E

    1980-01-01

    For the analysis of the impact of major chronic diseases on a population, a life table model is proposed in which the age at death due to specific cause (chronic disease) is postponed. Even though many of the major causes of death related to intrinsic aging processes are impossible to eliminate, these causes might be significantly delayed or retarded. To illustrate the use of this model, the effects of a delay of 5, 10, and 15 years in deaths due to three chronic degenerative diseases (cancer...

  16. A live-attenuated chimeric porcine circovirus type 2 (PCV2) vaccine is transmitted to contact pigs but is not upregulated by concurrent infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV) and is efficacious in a PCV2b-PRRSV-PPV challenge model

    OpenAIRE

    Opriessnig, T.; Shen, H. G.; Pal, N; Ramamoorthy, S.; Huang, Y. W.; Lager, K M; Beach, N. M.; Halbur, P G; Meng, X. J.

    2011-01-01

    The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine p...

  17. 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.

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

    International Nuclear Information System (INIS)

    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 (3H2O) 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 3H2O. 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 3H2O 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. • Surfactants increased penetration

  19. The Porcine Immunology and Nutrition Resource Database

    Science.gov (United States)

    Diverse genomics-based databases have been developed to facilitate research with human and rodent models. Current porcine gene databases, however, lack the nutritional and immunological orientation and robust annotation to design effective molecular tools to study relevant pig models. To address t...

  20. Lentiviral vector gene transfer to porcine airways.

    Science.gov (United States)

    Sinn, Patrick L; Cooney, Ashley L; Oakland, Mayumi; Dylla, Douglas E; Wallen, Tanner J; Pezzulo, Alejandro A; Chang, Eugene H; McCray, Paul B

    2012-01-01

    In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE) and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE). Interestingly, feline immunodeficiency virus (FIV)-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1-based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF).Molecular Therapy - Nucleic Acids (2012) 1, e56; doi:10.1038/mtna.2012.47; published online 27 November 2012. PMID:23187455

  1. Bioimpedance modeling to monitor astrocytic response to chronically implanted electrodes

    Science.gov (United States)

    McConnell, G. C.; Butera, R. J.; Bellamkonda, R. V.

    2009-10-01

    The widespread adoption of neural prosthetic devices is currently hindered by our inability to reliably record neural signals from chronically implanted electrodes. The extent to which the local tissue response to implanted electrodes influences recording failure is not well understood. To investigate this phenomenon, impedance spectroscopy has shown promise for use as a non-invasive tool to estimate the local tissue response to microelectrodes. Here, we model impedance spectra from chronically implanted rats using the well-established Cole model, and perform a correlation analysis of modeled parameters with histological markers of astroglial scar, including glial fibrillary acid protein (GFAP) and 4',6-diamidino-2- phenylindole (DAPI). Correlations between modeled parameters and GFAP were significant for three parameters studied: Py value, Ro and |Z|1 kHz, and in all cases were confined to the first 100 µm from the interface. Py value was the only parameter also correlated with DAPI in the first 100 µm. Our experimental results, along with computer simulations, suggest that astrocytes are a predominant cellular player affecting electrical impedance spectra. The results also suggest that the largest contribution from reactive astrocytes on impedance spectra occurs in the first 100 µm from the interface, where electrodes are most likely to record electrical signals. These results form the basis for future approaches where impedance spectroscopy can be used to evaluate neural implants, evaluate strategies to minimize scar and potentially develop closed-loop prosthetic devices.

  2. The Effects of Negative Pressure by External Tissue Expansion Device on Epithelial Cell Proliferation, Neo-Vascularization and Hair Growth in a Porcine Model

    Science.gov (United States)

    Hsiao, Hui-Yi; Liu, Jia-Wei; Brey, Eric M.; Cheng, Ming-Huei

    2016-01-01

    While pre-treating a fat transplant recipient site with negative pressure has shown promise for increasing the fat survival rate, the underlying mechanisms have not been investigated, partly due to challenges related to immobilization of vacuum domes on large animal subjects. The aim of this study was to examine the effect of negative pressure treatment by External Tissue Expansion Device (ETED) on fat grating recipient sites in a porcine model. The ETED was designed to provide negative pressure on the dorsum of swine. Pressure treatment (-70 mmHg) was applied for 1 or 3 hours every other day for 10 and 20 treatments. The treated areas (3.5 cm in diameter) were harvested and examined for histological changes, vessel density, cell proliferation (Ki67) and growth factor expression (FGF-1, VEGF and PDGB-bb). The application of the ETED increased epidermis thickness even after 1-hour treatments repeated 10 times. The results of Ki67 analysis suggested that the increasing thickness was due to cell proliferation in the epidermis. There was a more than two-fold increase in the vessel density, indicating that the ETED promotes vascularization. Unexpectedly, the treatment also increased the number of hair follicles. Negative pressure provided by the ETED increases the thickness of epidermis section of tissue, cell proliferation and vessel density. The porcine model provides a better representation of the effect of the ETED on skin tissue compared to small animal models and provides an environment for studying the mechanisms underlying the clinical benefits of negative pressure treatment. PMID:27128731

  3. The Effects of Negative Pressure by External Tissue Expansion Device on Epithelial Cell Proliferation, Neo-Vascularization and Hair Growth in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    Hui-Yi Hsiao

    Full Text Available While pre-treating a fat transplant recipient site with negative pressure has shown promise for increasing the fat survival rate, the underlying mechanisms have not been investigated, partly due to challenges related to immobilization of vacuum domes on large animal subjects. The aim of this study was to examine the effect of negative pressure treatment by External Tissue Expansion Device (ETED on fat grating recipient sites in a porcine model. The ETED was designed to provide negative pressure on the dorsum of swine. Pressure treatment (-70 mmHg was applied for 1 or 3 hours every other day for 10 and 20 treatments. The treated areas (3.5 cm in diameter were harvested and examined for histological changes, vessel density, cell proliferation (Ki67 and growth factor expression (FGF-1, VEGF and PDGB-bb. The application of the ETED increased epidermis thickness even after 1-hour treatments repeated 10 times. The results of Ki67 analysis suggested that the increasing thickness was due to cell proliferation in the epidermis. There was a more than two-fold increase in the vessel density, indicating that the ETED promotes vascularization. Unexpectedly, the treatment also increased the number of hair follicles. Negative pressure provided by the ETED increases the thickness of epidermis section of tissue, cell proliferation and vessel density. The porcine model provides a better representation of the effect of the ETED on skin tissue compared to small animal models and provides an environment for studying the mechanisms underlying the clinical benefits of negative pressure treatment.

  4. The Effects of Negative Pressure by External Tissue Expansion Device on Epithelial Cell Proliferation, Neo-Vascularization and Hair Growth in a Porcine Model.

    Science.gov (United States)

    Hsiao, Hui-Yi; Liu, Jia-Wei; Brey, Eric M; Cheng, Ming-Huei

    2016-01-01

    While pre-treating a fat transplant recipient site with negative pressure has shown promise for increasing the fat survival rate, the underlying mechanisms have not been investigated, partly due to challenges related to immobilization of vacuum domes on large animal subjects. The aim of this study was to examine the effect of negative pressure treatment by External Tissue Expansion Device (ETED) on fat grating recipient sites in a porcine model. The ETED was designed to provide negative pressure on the dorsum of swine. Pressure treatment (-70 mmHg) was applied for 1 or 3 hours every other day for 10 and 20 treatments. The treated areas (3.5 cm in diameter) were harvested and examined for histological changes, vessel density, cell proliferation (Ki67) and growth factor expression (FGF-1, VEGF and PDGB-bb). The application of the ETED increased epidermis thickness even after 1-hour treatments repeated 10 times. The results of Ki67 analysis suggested that the increasing thickness was due to cell proliferation in the epidermis. There was a more than two-fold increase in the vessel density, indicating that the ETED promotes vascularization. Unexpectedly, the treatment also increased the number of hair follicles. Negative pressure provided by the ETED increases the thickness of epidermis section of tissue, cell proliferation and vessel density. The porcine model provides a better representation of the effect of the ETED on skin tissue compared to small animal models and provides an environment for studying the mechanisms underlying the clinical benefits of negative pressure treatment. PMID:27128731

  5. Do telemonitoring projects of heart failure fit the Chronic Care Model?

    OpenAIRE

    Willemse, Evi; Adriaenssens, Jef; Dilles, Tinne; Remmen, Roy

    2014-01-01

    This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner.Background: The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation.Methods: This...

  6. 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.; Liu, Q.

    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...... piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations....... 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-gamma secreting cells, and cytotoxic T lymphocyte assays...

  7. PET Imaging of Serotonin Transporters With 4-[(18)F]-ADAM in a Parkinsonian Rat Model With Porcine Neural Xenografts.

    Science.gov (United States)

    Chiu, Chuang-Hsin; Li, I-Hsun; Weng, Shao-Ju; Huang, Yuahn-Sieh; Wu, Shinn-Chih; Chou, Ta-Kai; Huang, Wen-Sheng; Liao, Mei-Hsiu; Shiue, Chyng-Yann; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the nigrostriatal pathway. Apart from effective strategies to halt the underlying neuronal degeneration, cell replacement now offers novel prospects for PD therapy. Porcine embryonic neural tissue has been considered an alternative source to human fetal grafts in neurodegenerative disorders because its use avoids major practical and ethical issues. This study was undertaken to evaluate the effects of embryonic day 27 (E27) porcine mesencephalic tissue transplantation in a PD rat model using animal positron emission tomography (PET) coupled with 4-[(18)F]-ADAM, a serotonin transporter (SERT) imaging agent. The parkinsonian rat was induced by injecting 6-hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal pathway. The apomorphine-induced rotation behavioral test and 4-[(18)F]-ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the second week following 6-OHDA lesioning, the parkinsonian rat rotates substantially on apomorphine-induced contralateral turning. In addition, the mean striatal-specific uptake ratio (SUR) of 4-[(18)F]-ADAM decreased by 44%. After transplantation, the number of drug-induced rotations decreased markedly, and the mean SUR of 4-[(18)F]-ADAM and the level of SERT immunoreactivity (SERT-ir) in striatum were partially restored. The mean SUR level was restored to 71% compared to that for the contralateral intact side, which together with the abundant survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery at the fourth week postgraft. In regard to the extent of donor-derived cells, we found the neurons of the xenografts from E27 transgenic pigs harboring red fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted area. Thus, transplanted E27 porcine mesencephalic tissue may restore dopaminergic and serotonergic systems in the parkinsonian rat

  8. 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; Kiilgaard, Jens Folke; la Cour, Morten

    2010-01-01

    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 by...... perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  9. 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; Kiilgaard, Jens Folke; Dornonville de la Cour, Morten

    2010-01-01

    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 by...... perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  10. Quantification of iron in the presence of calcium with dual-energy computed tomography (DECT) in an ex vivo porcine plaque model

    Science.gov (United States)

    Wang, Jia; Garg, Nitin; Duan, Xinhui; Liu, Yu; Leng, Shuai; Yu, Lifeng; Ritman, Erik L.; Kantor, Birgit; McCollough, Cynthia H.

    2011-11-01

    Iron deposits secondary to microbleeds often co-exist with calcium in coronary plaques. The purpose of this study was to quantify iron in the presence of calcium in an ex vivo porcine arterial plaque model using a clinical dual-energy CT (DECT) scanner. A material decomposition method to quantify the mass fractions of iron and calcium within a mixture using DECT was developed. Mixture solutions of known iron and calcium concentrations were prepared to calibrate and validate the DECT-based algorithm. Simulated plaques with co-existing iron and calcium were created by injecting the mixture solutions into the vessel wall of porcine carotid arteries and aortas. These vessel regions were harvested and scanned using a clinical DECT system and iron mass fraction was calculated for each sample. Iron- and calcium-specific staining was conducted on 5 µm thick histological sections of vessel samples to confirm the co-existence of iron and calcium in the simulated plaques. The proposed algorithm accurately quantified iron and calcium amounts in mixture solutions. Maps of iron mass fraction of 60 artery segments were obtained from CT images at two energies. The sensitivity for detecting the presence of iron was 83% and the specificity was 92% using a threshold at an iron mass fraction of 0.25%. Histological analysis confirmed the co-localization of iron and calcium within the simulated plaques. Iron quantification in the presence of calcium was feasible in excised arteries at an iron mass fraction of around 1.5% or higher using current clinical DECT scanners.

  11. Comparison of ablation zones among different tissues using 2450-MHz cooled-shaft microwave antenna: results in ex vivo porcine models.

    Directory of Open Access Journals (Sweden)

    Wenbin Zhou

    Full Text Available BACKGROUND: For complete tumor ablation in different tissues, it is necessary to investigate the exact coagulation zone of microwave ablation in different tissues. The aim of this study was to compare the extent of microwave ablation zone in muscle, liver and adipose tissue in ex vivo porcine models and assess the shape of microwave coagulation zone among these tissues. MATERIALS AND METHODS: Microwave ablations were performed in ex vivo porcine muscle, liver and adipose tissue using 2450-MHz cooled-shaft microwave antenna. The content of water, fat and protein in these three tissues was determined. Two power increments (40 and 80 W and five time increments (1, 3, 5, 7, and 10 minutes were used in this study. Diameters and shapes of the ablation zones were assessed on gross specimens. RESULTS: The average percentages of water, fat and protein in these three tissues were significantly different (P 0.05. The coagulation zones were all elliptical in muscle, liver and adipose tissue. When microwave ablation was performed in the tissue containing both muscle and adipose tissue, the coagulation zone was also elliptical. Regardless of the output power, the ellipticity index (EI value of 1 minute treatment duration was higher than that of 10 minutes treatment duration (P 0.05. CONCLUSION: The extent of microwave ablation zones was not significantly different among completely different tissues. Microwave ablations with ≥ 5 minutes time duration can induce coagulation zones with clinical desirable shape. Future clinical studies are still required to determine the role of microwave ablation in different tissues.

  12. 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) . PMID:21590723

  13. 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.

  14. 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. PMID:23313919

  15. Automated medical diagnosis with fuzzy stochastic models: monitoring chronic diseases.

    Science.gov (United States)

    Jeanpierre, Laurent; Charpillet, François

    2004-01-01

    As the world population ages, the patients per physician ratio keeps on increasing. This is even more important in the domain of chronic pathologies where people are usually monitored for years and need regular consultations. To address this problem, we propose an automated system to monitor a patient population, detecting anomalies in instantaneous data and in their temporal evolution, so that it could alert physicians. By handling the population of healthy patients autonomously and by drawing the physicians' attention to the patients-at-risk, the system allows physicians to spend comparatively more time with patients who need their services. In such a system, the interaction between the patients, the diagnosis module, and the physicians is very important. We have based this system on a combination of stochastic models, fuzzy filters, and strong medical semantics. We particularly focused on a particular tele-medicine application: the Diatelic Project. Its objective is to monitor chronic kidney-insufficient patients and to detect hydration troubles. During two years, physicians from the ALTIR have conducted a prospective randomized study of the system. This experiment clearly shows that the proposed system is really beneficial to the patients' health. PMID:15520535

  16. Modeling of radiation doses from chronic aqueous releases

    International Nuclear Information System (INIS)

    A general model and corresponding computer code were developed to calculate personnel dose estimates from chronic releases via aqueous pathways. Potential internal dose pathways are consumption of water, fish, crustacean, and mollusk. Dose prediction from consumption of fish, crustacean, or mollusk is based on the calculated radionuclide content of the water and applicable bioaccumulation factor. 70-year dose commitments are calculated for whole body, bone, lower large intestine of the gastrointestinal tract, and six internal organs. In addition, the code identifies the largest dose contributor and the dose percentages for each organ-radionuclide combination in the source term. The 1974 radionuclide release data from the Savannah River Plant were used to evaluate the dose models. The dose predicted from the model was compared to the dose calculated from radiometric analysis of water and fish samples. The whole body dose from water consumption was 0.45 mrem calculated from monitoring data and 0.61 mrem predicted from the model. Tritium contributed 99 percent of this dose. The whole body dose from fish consumption was 0.20 mrem calculated from monitoring data and 0.14 mrem from the model. Cesium-134,137 was the principal contributor to the 70-year whole body dose from fish consumption

  17. 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.

  18. 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 intr...

  19. 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 in...

  20. CT-based liver volumetry in a porcine model: impact on clinical volumetry prior to living donated liver transplantation

    International Nuclear Information System (INIS)

    Purpose: Exact preoperative determination of the liver volume is of great importance prior to hepatobiliary surgery, especially in living donated liver transplantation (LDLT). In the current literature, a strong correlation between preoperatively calculated and intraoperatively measured liver volumes has been described. Such accuracy seems questionable, primarily due to a difference in the perfusion state of the liver in situ versus after explantation. Purpose of the study was to asses the influence of the perfusion state on liver volume and the validity of the preoperative liver volumetry prior to LDLT. Methods: In an experimental study, 20 porcine livers were examined. The livers were weighted and their volumes were determined by water displacement prior and after fluid infusion to achieve a pressure physiologically found in the liver veins. The liver volumes in the different perfusion states were calculated based on CT-data. The calculated values were compared with the volume measured by water displacement and the weight of the livers. Results: Assessment of calculated CT volumes and water displacements at identical perfusion states showed a tight correlation and differed on average by 4 ± 5%. However, livers before and after fluid infusion showed a 33 ± 8% (350 ± 150 ml) difference in volume. Conclusion: CT-volumetry acquires highly accurate data as confirmed by water displacement studies. However, the perfusion state has major impact on liver volume, which has to be accounted for in clinical use. (orig.)

  1. Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

    OpenAIRE

    Ahn, Joong Hyun; Kim, Chi Hong; Kim, Yong Hyun; Kim, Seung Joon; Lee, Sook-Young; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak; Kwon, Soon Seog

    2007-01-01

    Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twen...

  2. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    OpenAIRE

    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 ...

  3. Telomere reprogramming and maintenance in porcine iPS cells.

    Directory of Open Access Journals (Sweden)

    Guangzhen Ji

    Full Text Available 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.

  4. 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 ...... of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity....

  5. 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.

  6. Evaluation of adenosine preconditioning with 99mTc-His10-annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

    International Nuclear Information System (INIS)

    Purpose: The goal of this study was to evaluate the feasibility of 99mTc-His10-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: 99mTc-His10-annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of 99mTc-His10-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. 99mTc-His10-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 99mTc-MIBI was also performed 1 day after His10-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: 99mTc-His10-annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of 99mTc-His10-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 His10-annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of 99mTc-His10-annexin was found in the risk area which showed no defects in the 99mTc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly diminished the level of apoptosis. Uptake of His10-annexin V in RI correlated with TUNEL-positive nuclei

  7. Structural Determination and Daily Variations of Porcine Milk Oligosaccharides

    OpenAIRE

    Tao, Nannan; Ochonicky, Karen L.; German, J Bruce; Donovan, Sharon M.; Lebrilla, Carlito B.

    2010-01-01

    Free milk oligosaccharides (OS) is a major component of mammalian milk. Swine are important agricultural species and biomedical models. Despite their importance, little is known of the OS profile of porcine milk. Herein, the porcine milk glycome was elucidated and monitored over the entire lactation period by liquid chromatography profiling and structural determination with mass spectrometry. Milk was collected from second parity sows (n=3) at farrowing and on days 1, 4, 7 and 24 of lactation...

  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 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...

  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. Chronic Myeloid Leukemia (CML) Mouse Model in Translational Research.

    Science.gov (United States)

    Peng, Cong; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without the loss of their capability to differentiate. CML is a clonal disease, originated at the level of Hematopoietic Stem Cells with the Philadelphia chromosome resulting from a reciprocal translocation between the chromosomes 9 and 22t(9;22)-(q34;q11). This translocation produces a fusion gene known as BCR-ABL which acquires uncontrolled tyrosine kinase activity, constantly turning on its downstream signaling molecules/pathways, and promoting proliferation of leukemia cell through anti-apoptosis and acquisition of additional mutations. To evaluate the role of each critical downstream signaling molecule of BCR-ABL and test therapeutic drugs in vivo, it is important to use physiological mouse disease models. Here, we describe a mouse model of CML induced by BCR-ABL retrovirus (MSCV-BCR-ABL-GFP; MIG-BCR-ABL) and how to use this model in translational research.Moreover, to expand the application of this retrovirus induced CML model in a lot of conditional knockout mouse strain, we modified this vector to a triple gene coexpression vector in which we can co-express BCR-ABL, GFP, and a third gene which will be tested in different systems. To apply this triple gene system in conditional gene knockout strains, we can validate the CML development in the knockout mice and trace the leukemia cell following the GFP marker. In this protocol, we also describe how we utilize this triple gene system to prove the function of Pten as a tumor suppressor in leukemogenesis. Overall, this triple gene system expands our research spectrum in current conditional gene knockout strains and benefits our CML translational research. PMID:27150093

  11. 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

    International Nuclear Information System (INIS)

    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

  12. Value of myocardial perfusion imaging in evaluating effects of releasing base fibroblast growth factor stent on cardiac repair in a porcine myocardial infarction model

    International Nuclear Information System (INIS)

    Objective: Basic fibroblast growth factor (b-FGF) induces endothelial cell and smooth muscle cell proliferation and stimulates angiogenesis. The objective of this study was to evaluate the impact of intramyocardial administration of degradable releasing b-FGF stent on myocardial blood flow, angiogenesis and ventricular function in a porcine acute myocardial infarction model. Methods: Acute myocardial infarction was induced by ligating the left anterior descending artery (LAD) distal to its first diagonal branch in 12 minitype porcines. Mechanical transmyocardial revascularization (TMR) was performed by creating 3 transmural channels in the LAD infarct and peri-infarct zone. Twelve animals were divided into two groups: TMR+naked stent ( control group, n=6), TMR + b-FGF stent ( b-FGF group, n=6). In both groups, 3 naked stents and 3 b-FGF stents were implanted into TMR channels respectively. 99Tcm-methoxyisobutyli-sonitrile (MIBI) myocardial perfusion imaging was performed to evaluate the change in myocardial blood flow as baseline and at 6 weeks after the procedure. Echocardiography and immunohistochemical studies were also performed. All data were evaluated with SPSS 11.5. The differences of the two groups were analyzed with the independent-sample t-test. Results: Treatment with b-FGF decreased the magnitude of infarct mass [(34.33 ± 4.18) vs (24.33 ± 2.16) g, t=5.03, P<0.05] and per-segment reversibility score ( reflecting the magnitude of improved ischemia, 13.83 ± 2.86 vs 8.33 ± 1.37, t=5.06, P<0.05). There was also fraction shortening [FS, (31.13 ± 0.99) % vs ( 27.11 ± 0.71) %, t=8.12, P<0.05] and increased microvessel density in the peri-infarct zone and infarct zone respectively [(6201 ± 443) vs (2654 ± 373 ) pixel/high power field, t=15.01, P<0.05]. Conclusions: Intramyocardial administration of degradable releasing b-FGF stent increased the regional myocardial blood flow, reduced infarct size and improved ventricular function in acute myocardial

  13. 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

  14. Effects of β-radiation using a Holmium-166 coated balloon on neointimal hyperplasia in a porcine coronary stent restenosis model

    International Nuclear Information System (INIS)

    Brachytherapy is a promising method of preventing and treating coronary stent restenosis. The present study was designed to observe the therapeutic effects of a radioactive balloon loaded with Holmium-166 (166Ho) in a porcine coronary stent restenosis model. A radioisotope of 166Ho was coated onto the balloon surface using polyurethane (20 Gy at 0.5 mm depth). Stent overdilation injuries were induced in 2 coronary arteries in each pig (n=8). Four weeks after the injury, control balloon dilation was performed in one coronary artery (Group I) and radiation therapy using the 166Ho coated balloon in the other coronary artery (Group II) in each pig. Follow-up coronary angiography and histopathologic assessment were performed at 4 weeks after the radiation therapy or the control balloon dilations. With regard to complete blood cell counts, liver function tests, lipid profiles and coagulation tests, there were no differences between the baseline and after radiation. On quantitative coronary angiographic analysis, reference and target artery diameter showed no differences between the 2 groups before, or 4 and 8 weeks after stenting. On histopathologic analysis of groups I and II, the injury score was 1.34±0.09 and 1.32±0.10, the area of internal elastic lamina was 4.99±0.17 mm2 and 4.82±0.20 mm2, and the luminal area was 3.20±0.10 mm2 and 3.45±0.14 mm2, respectively (p=NS). The neointimal area was 1.78±0.11 mm2 in group I and 1.36±0.12 mm2 in group II (p=0.017), and the histopathologic area of stenosis was 35.1±1.6% in group I and 27.6±1.9% in group II (p=0.005). In conclusion, β-radiation of the stented porcine coronary artery using a radioactive 166Ho coated balloon inhibited stent restenosis without any side effects. (author)

  15. Enhanced itch elicited by capsaicin in a chronic itch model.

    Science.gov (United States)

    Yu, Guang; Yang, Niuniu; Li, Fengxian; Chen, Meijuan; Guo, Changxiong J; Wang, Changming; Hu, Danyou; Yang, Yan; Zhu, Chan; Wang, Zhongli; Shi, Hao; Gegen, Tana; Tang, Ming; He, Qian; Liu, Qin; Tang, Zongxiang

    2016-01-01

    Chronic itch (pruritus) is an important clinical problem. However, the underlying molecular basis has yet to be understood. The Transient Receptor Potential Vanilloid 1 channel is a heat-sensitive cation channel expressed in primary sensory neurons and involved in both thermosensation and pain, but its role in chronic itch remains elusive. Here, we for the first time revealed an increased innervation density of Transient Receptor Potential Vanilloid 1-expressing sensory fibers in the skin afflicted with chronic itch. Further analysis indicated that this phenomenon is due to an expansion of Transient Receptor Potential Vanilloid 1-expressing sensory neurons under chronic itch conditions. As a functional correlates of this neuronal expansion, we observed an enhanced neuronal responsiveness to capsaicin under the dry skin conditions. Importantly, the neuronal hypersensitivity to capsaicin results in itch, rather than pain sensation, suggesting that the up-regulated Transient Receptor Potential Vanilloid 1 underlies the pain-to-itch switch under chronic itchy conditions. The study shows that there are different mechanisms of chronic pain and itching, and Transient Receptor Potential Vanilloid 1 plays an important role in chronic itch. PMID:27118771

  16. Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation.

    Science.gov (United States)

    White, C W; Lillico, R; Sandha, J; Hasanally, D; Wang, F; Ambrose, E; Müller, A; Rachid, O; Li, Y; Xiang, B; Le, H; Messer, S; Ali, A; Large, S R; Lee, T W; Dixon, I M C; Lakowski, T M; Simons, K; Arora, R C; Tian, G; Nagendran, J; Hryshko, L V; Freed, D H

    2016-03-01

    Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation. PMID:26663659

  17. The effect of interspinous ligament integrity on adjacent segment instability after lumbar instrumentation and laminectomy--an experimental study in porcine model.

    Science.gov (United States)

    Chen, Lih-Huei; Lai, Po-Liang; Tai, Ching-Lung; Niu, Chi-Chien; Fu, Tsai-Sheng; Chen, Wen-Jer

    2006-01-01

    Eight fresh porcine lumbar spines received a posterior instrumentation at L4-L5 using pedicle screw-rod system. Each specimen was tested utilizing laminectomies of varying extent. Group A (Integrity) preserved the spinous process and interspinous ligament; Group B (Partial laminectomy) removed the inferior portion of L4 spinous process and preserved the interspinous ligament of L3-L4; Group C (Complete laminectomy) removed the entire L4 spinous process. Hydraulic testing machine was used to generate an increasing moment up to 8400 N mm in flexion and extension. The intervertebral displacement on the superior adjacent disc between L3-L4 was measured using an extensometer. Under extension, no significant difference in the intervertebral displacement was observed among three different models of laminectomy. However, under flexion, the intervertebral displacement on adjacent disc with complete laminectomy was statistically larger than those of integrity and partial laminectomies (P=0.000976 and P=0.0363, respectively). No difference was found between integrity and partial laminectomy groups (P>0.05). This study implies that an instrumented spine with integrity of posterior complex is less likely to develop adjacent instability than a spine with destruction of the anchoring point for supraspinous ligament. PMID:16971744

  18. 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. PMID:26060888

  19. A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model.

    Science.gov (United States)

    Patel, Ami; Tikoo, Suresh; Kobinger, Gary

    2010-01-01

    Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5. PMID:21179494

  20. 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.

  1. 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)

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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 of...... 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...

  4. 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.

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

    OpenAIRE

    Egloff, Niklaus

    2013-01-01

    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 be...

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

    OpenAIRE

    Egloff N; Hirschi A; von Känel R

    2013-01-01

    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 subj...

  7. Challenges of Change: A Qualitative Study of Chronic Care Model Implementation

    OpenAIRE

    Hroscikoski, Mary C.; Solberg, Leif I.; Sperl-Hillen, JoAnn M.; Harper, Peter G.; McGrail, Michael P.; Crabtree, Benjamin F.

    2006-01-01

    PURPOSE The Chronic Care Model (CCM) provides a conceptual framework for transforming health care for patients with chronic conditions; however, little is known about how to best design and implement its specifics. One large health care organization that tried to implement the CCM in primary care provided an opportunity to study these issues.

  8. Effects of intraperitoneal injection of microencapsulated Sertoli cells on chronic and presymptomatic dystrophic mice

    OpenAIRE

    Sara Chiappalupi; Giovanni De Luca; Francesca Mancuso; Luca Madaro; Francesca Fallarino; Carmine Nicoletti; Mario Calvitti; Iva Arato; Giulia Falabella; Laura Salvadori; Antonio Di Meo; Antonello Bufalari; Stefano Giovagnoli; Riccardo Calafiore; Rosario Donato

    2015-01-01

    We report data about the effects of intraperitoneal (i.p.) injection of specific pathogen-free (SPF) porcine Sertoli cells (SeC) encapsulated into clinical grade alginate-based microcapsules (SeC-MC) on muscles of chronic and presymptomatic dystrophic, mdx mice. Mdx mouse is the best characterized animal model of Duchenne muscular dystrophy (DMD), an X-linked lethal myopathy due to mutation in the gene of dystrophin, which is crucial for myofiber integrity during muscle contraction. Our data ...

  9. Recruitment bias in chronic pain research: whiplash as a model.

    Science.gov (United States)

    Nijs, Jo; Inghelbrecht, Els; Daenen, Liesbeth; Hachimi-Idrissi, Said; Hens, Luc; Willems, Bert; Roussel, Nathalie; Cras, Patrick; Wouters, Kristien; Bernheim, Jan

    2011-11-01

    In science findings which cannot be extrapolated to other settings are of little value. Recruitment methods vary widely across chronic whiplash studies, but it remains unclear whether this generates recruitment bias. The present study aimed to examine whether the recruitment method accounts for differences in health status, social support, and personality traits in patients with chronic whiplash-associated disorders (WAD). Two different recruitment methods were compared: recruiting patients through a local whiplash patient support group (group 1) and local hospital emergency department (group 2). The participants (n=118) filled in a set of questionnaires: the Neck Disability Index, Medical Outcome Study Short-Form General Health Survey, Anamnestic Comparative Self-Assessment measure of overall well-being, Symptom Checklist-90, Dutch Personality Questionnaire, and the Social Support List. The recruitment method (either through the local emergency department or patient support group) accounted for the differences in insufficiency, somatization, disability, quality of life, self-satisfaction, and dominance (all p values recruitment methods generated chronic WAD patients comparable for psychoneurotism, social support, self-sufficiency, (social) inadequacy, rigidity, and resentment (p>.01). The recruitment of chronic WAD patients solely through patient support groups generates bias with respect to the various aspects of health status and personality, but not social support. In order to enhance the external validity of study findings, chronic WAD studies should combine a variety of recruitment procedures. PMID:21853277

  10. The Use of Bovine Pericardial Buttress on Linear Stapler Fails to Reduce Pancreatic Fistula Incidence in a Porcine Pancreatic Transection Model

    Directory of Open Access Journals (Sweden)

    A. Maciver

    2011-01-01

    Full Text Available We investigate the effectiveness of buttressing the surgical stapler to reduce postoperative pancreatic fistulae in a porcine model. As a pilot study, pigs (n=6 underwent laparoscopic distal pancreatectomy using a standard stapler. Daily drain output and lipase were measured postoperative day 5 and 14. In a second study, pancreatic transection was performed to occlude the proximal and distal duct at the pancreatic neck using a standard stapler (n=6, or stapler with bovine pericardial strip buttress (n=6. Results. In pilot study, 3/6 animals had drain lipase greater than 3x serum on day 14. In the second series, drain volumes were not significantly different between buttressed and control groups on day 5 (55.3 ± 31.6 and 29.3 ± 14.2 cc, resp., nor on day 14 (9.5 ± 4.2 cc and 2.5 ± 0.8 cc, resp., P=0.13. Drain lipase was not statistically significant on day 5 (3,166 ± 1,433 and 6,063 ± 1,872 U/L, resp., P=0.25 or day 14 (924 ± 541 and 360 ± 250 U/L. By definition, 3/6 developed pancreatic fistula; only one (control demonstrating a contained collection arising from the staple line. Conclusion. Buttressed stapler failed to protect against pancreatic fistula in this rigorous surgical model.

  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. 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

  13. 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

  14. 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 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

  15. 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.

  16. Radiofrequency ablation in a porcine liver model: Effects of transcatheter arterial embolization with iodized oil on ablation time, maximum output, and coagulation diameter as well as angiographic characteristics

    Institute of Scientific and Technical Information of China (English)

    Motoki Nakai; Morio Sato; Shinya Sahara; Nobuyuki Kawai; Hirohiko Tanihata; Masashi Kimura; Masaki Terada

    2007-01-01

    AIM:To evaluate the effects of combined radiofrequency ablation and transcatheter arterial embolization with iodized oil on ablation time, maximum output, coagulation diameter, and portal angiography in a porcine liver model.METHODS: Radiofrequency ablation (RFA) was applied to in vivo livers of 10 normal pigs using a 17-gauge 3.0cm expandable LeVeen RF needle electrode with or without transcatheter arterial embolization (TAE) with iodized oil (n = 5). In each animal, 2 areas in the liver were ablated. Direct portography was performed before and after RFA. Ablation was initiated at an output of 30 W, and continued with an increase of 10 W per minute until rolloff occurred. Ablation time and maximum output until roll-off, and coagulated tissue diameter were compared between the 2 groups. Angiographic changes on portography before and after ablation were also reviewed.RESULTS: For groups with and without TAE with iodized oil, the ablation times until roll-off were 320.6 ± 30.9seconds and 445.1 ± 35.9 seconds, respectively, maximum outputs were 69.0 ± 7.38 W and 87.0 ± 4.83 Wand maximal diameters of coagulation were 41.7 ± 3.85mm and 33.2 ± 2.28 mm. Significant reductions of ablation time and maximum output, and significantly largercoagulation diameter were obtained with RFA following TAE with iodized oil compared to RFA alone. Portography after RFA following TAE with iodized oil revealed more occlusion of the larger portal branches than with RFA alone.CONCLUSION: RFA following TAE with iodized oil can increase the volume of coagulation necrosis with lower output and shorter ablation time than RFA alone in normal pig liver tissue.

  17. 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.

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

    International Nuclear Information System (INIS)

    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.

  19. 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.

  20. Chronic Low Back Pain: Toward an Integrated Psychosocial Assessment Model.

    Science.gov (United States)

    Strong, Jenny; And Others

    1994-01-01

    Integrated six dimensions of chronic low back pain (pain intensity, functional disability, attitudes toward pain, pain coping strategies, depression, illness behavior) to provide multidimensional patient profile. Data from 100 patients revealed presence of three distinct patient groups: patients who were in control, patients who were depressed and…

  1. Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs

    OpenAIRE

    Basel, Matthew T; Balivada, Sivasai; Beck, Amanda P; Kerrigan, Maureen A.; Pyle, Marla M; Dekkers, Jack C.M.; Wyatt, Carol R.; Rowland, Robert R. R.; Anderson, David E.; Bossmann, Stefan H; Troyer, Deryl L.

    2012-01-01

    Abstract Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodefici...

  2. Simulation of between-farm transmission of porcine reproductive and respiratory syndrome virus in Ontario, Canada using the North American Animal Disease Spread Model.

    Science.gov (United States)

    Thakur, Krishna K; Revie, Crawford W; Hurnik, Daniel; Poljak, Zvonimir; Sanchez, Javier

    2015-03-01

    Porcine reproductive and respiratory syndrome (PRRS), a viral disease of swine, has major economic impacts on the swine industry. The North American Animal Disease Spread Model (NAADSM) is a spatial, stochastic, farm level state-transition modeling framework originally developed to simulate highly contagious and foreign livestock diseases. The objectives of this study were to develop a model to simulate between-farm spread of a homologous strain of PRRS virus in Ontario swine farms via direct (animal movement) and indirect (sharing of trucks between farms) contacts using the NAADSM and to compare the patterns and extent of outbreak under different simulated conditions. A total of 2552 swine farms in Ontario province were allocated to each census division of Ontario and geo-locations of the farms were randomly generated within the agriculture land of each Census Division. Contact rates among different production types were obtained using pig movement information from four regions in Canada. A total of 24 scenarios were developed involving various direct (movement of infected animals) and indirect (pig transportation trucks) contact parameters in combination with alternating the production type of the farm in which the infection was seeded. Outbreaks were simulated for one year with 1000 replications. The median number of farms infected, proportion of farms with multiple outbreaks and time to reach the peak epidemic were used to compare the size, progression and extent of outbreaks. Scenarios involving spread only by direct contact between farms resulted in outbreaks where the median percentage of infected farms ranged from 31.5 to 37% of all farms. In scenarios with both direct and indirect contact, the median percentage of infected farms increased to a range from 41.6 to 48.6%. Furthermore, scenarios with both direct and indirect contact resulted in a 44% increase in median epidemic size when compared to the direct contact scenarios. Incorporation of both animal

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Le «Chronic care model» en médecine de famille en Suisse

    OpenAIRE

    Steurer-Stey, C.; Frei, A; Rosemann, T

    2010-01-01

    The Chronic care model in Swiss primary care The care of patients with chronic disease is one of the most urgent medical challenges of actual society. The chronic care model (CCM) is an organizational, proactive approach for chronic disease in primary care. The system creates practical, supportive, evidence-based interactions between an informed, activated patient and a proactive practice team. CCM identifies six essential elements of high-quality health care : community ; heal...

  5. Holistic interaction model for peoble living with a chronic disease

    OpenAIRE

    Villalba Mora, Elena

    2008-01-01

    Ambient Intelligence (AmI) allows the intelligent and natural interaction between the context and individuals. This paradigm will facilitate user support through novel medical protocol design for chronic disease treatment, based on the healthy lifestyle promotion. Cardiovascular Diseases (CVD) account for 45% of all deaths in the western world according to the 2004 World Health Organization statistic report. Heart Failure (HF), CVD’s primary paradigm, mainly affects people older than 65. The ...

  6. 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. PMID:25990367

  7. Laparo- and thoracoscopic aortic aneurysm neck optimization and treatment of potential endoleaks type IA and II in a porcine model

    Directory of Open Access Journals (Sweden)

    Brian O. Kloster

    2016-02-01

    Conclusion: Using these minimal invasive endoscopic approaches, it seems feasible to externally band aneurysm necks and ligate aortic side branches in a pig model. These procedures could potentially be considered as alternatives to OCs in controlling endoleaks and in improving the safety of endovascular interventions. As endoscopic aortic surgery is challenging a learning curve is expected. Practicing the described procedures using this model, can be used as a learning tool prior to similar interventions on humans.

  8. Fed State Prior to Hemorrhagic Shock and Polytrauma in a Porcine Model Results in Altered Liver Transcriptomic Response

    OpenAIRE

    Determan, Charles; Anderson, Rebecca; Becker, Aaron; Witowski, Nancy; Lusczek, Elizabeth; Mulier, Kristine; Beilman, Greg J.

    2014-01-01

    Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic re...

  9. 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.

  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

    genetics. Pigs, although not easily kept for laboratory research, are, however, readily available for biomedical research through the large scale industrial production of pigs produced for human consumption. Recent research has facilitated the biological experimentation with pigs, and helped develop the...... pig into a novel model organism for biomedical research. This toolbox includes the near completion of the pig genome, catalogues of genes and genetic variation in pigs, extensive characterization of pig proteomes and transcriptomes, as well as the development of transgenic disease models. The aim of...... this review is to highlight the current progress of these ongoing areas of research, which are mandatory for successful development of biomedical pig models that are in demand for understanding human biology in health and disease....

  11. 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

  12. 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

  13. Endovascular middle cerebral arterial occlusion in a nonhuman primate model of chronic stroke

    Institute of Scientific and Technical Information of China (English)

    Qiang Wang; Tong Zhang; Chunyu Zhao; Bin Du; Feng Gao; Mei Wen; Weijian Jiang

    2011-01-01

    No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.

  14. Facilitators and barriers of implementing the chronic care model in primary care: a systematic review

    OpenAIRE

    Kadu, Mudathira K; Stolee, Paul

    2015-01-01

    Background The Chronic Care Model (CCM) is a framework developed to redesign care delivery for individuals living with chronic diseases in primary care. The CCM and its various components have been widely adopted and evaluated, however, little is known about different primary care experiences with its implementation, and the factors that influence its successful uptake. The purpose of this review is to synthesize findings of studies that implemented the CCM in primary care, in order to identi...

  15. Using Mobile Health to Support the Chronic Care Model: Developing an Institutional Initiative

    OpenAIRE

    Shantanu Nundy; Jonathan J. Dick; Goddu, Anna P.; Patrick Hogan; Lu, Chen-Yuan E.; Solomon, Marla C; Arnell Bussie; Chin, Marshall H; Peek, Monica E.

    2012-01-01

    Background. Self-management support and team-based care are essential elements of the Chronic Care Model but are often limited by staff availability and reimbursement. Mobile phones are a promising platform for improving chronic care but there are few examples of successful health system implementation. Program Development. An iterative process of program design was built upon a pilot study and engaged multiple institutional stakeholders. Patients identified having a “human face” to the pilot...

  16. Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models

    OpenAIRE

    Setlow, Barry; Mendez, Ian A.; Mitchell, Marci R; Simon, Nicholas W.

    2009-01-01

    Drug addicted individuals demonstrate high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human dru...

  17. In vivo functional chronic imaging of a small animal model using optical-resolution photoacoustic microscopy

    OpenAIRE

    Hu, Song; Maslov, Konstantin; Wang, Lihong V.

    2009-01-01

    Optical-resolution photoacoustic microscopy (OR-PAM) has been validated as a valuable tool for label-free volumetric microvascular imaging. More importantly, the advantages of noninvasiveness and measurement consistency suggest the use of OR-PAM for chronic imaging of intact microcirculation. Here, such chronic imaging is demonstrated for the first time by monitoring the healing process of laser-induced microvascular lesions in a small animal model in vivo. The central part of a 1 mm by 1 mm ...

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

    OpenAIRE

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

    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 hypothal...

  19. Biological Analysis of Human CML Stem Cells; Xenograft Model of Chronic Phase Human Chronic Myeloid Leukemia.

    Science.gov (United States)

    Abraham, Sheela A

    2016-01-01

    Xenograft mouse models have been instrumental in expanding our knowledge of hematopoiesis and can provide a functional description of stem cells that possess engrafting potential. Here we describe methodology outlining one way of analyzing human malignant cells that are able to engraft immune compromised mice. Using models such as these will allow researchers to gain valuable insight into the primitive leukemic subtypes that evade current therapy regimes and are critical to understand, in order to eradicate malignancy. PMID:27581148

  20. 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...... provide novel insights that may further the current understanding of the molecular mechanisms underlying human obesity....

  1. Biomechanical comparison of lumbar spine instability between laminectomy and bilateral laminotomy for spinal stenosis syndrome – an experimental study in porcine model

    OpenAIRE

    Chen Lih-Huei; Chen Weng-Pin; Hsieh Pang-Hsing; Tai Ching-Lung; Chen Wen-Jer; Lai Po-Liang

    2008-01-01

    Abstract Background The association of lumbar spine instability between laminectomy and laminotomy has been clinically studied, but the corresponding in vitro biomechanical studies have not been reported. We investigated the hypothesis that the integrity of the posterior complex (spinous process-interspinous ligament-spinous process) plays an important role on the postoperative spinal stability in decompressive surgery. Methods Eight porcine lumbar spine specimens were studied. Each specimen ...

  2. 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

  3. 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

  4. 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.

  5. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    OpenAIRE

    Rothman, A.M.K.; Arnold, N D; Chang, W.; Watson, O.; Swift, A J; Condliffe, R; Elliot, C A; Kiely, D. G.; Suvarna, S K; Gunn, J.; Lawrie, A.

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to de...

  6. Development of a Porcine Delayed Wound-Healing Model and Its Use in Testing a Novel Cell-Based Therapy

    International Nuclear Information System (INIS)

    Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

  7. Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Gaurav Patki

    2009-12-01

    Full Text Available Mitochondrial oxidative stress and dysfunction has been implicated as a possible mechanism for the onset and progression of Parkinson-like neurodegeneration. However, long-term mitochondrial defects in chronic animal neurodegenerative models have not been demonstrated. In this study, we investigated the function of striatal mitochondria 6 weeks after the induction of a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson’s disease (MPD. Although severe depression of mitochondrial respiration was observed immediately after acute administrations of MPTP, we failed to detect a significant mitochondrial inhibition in presence of striatal dopamine deficit 6 weeks after the chronic MPD induction in young adult mice. In contrast, when aged mice were chronically treated with MPTP and at 6 weeks post-treatment, these animals suffered an inhibition of the basal (state 4 and ADP-stimulated (state 3 respiration and a fall in ATP level in the striatal mitochondria. The aged chronic MPD also brought about a sustained diminution of striatal anti-oxidant enzyme levels including that of superoxide dismutases and cytochrome c. The mitochondrial deficits in the striatum of aged chronic MPD 6 weeks after treatment were further correlated with significant losses of striatal dopamine, tyrosine hydroxylase, dopamine uptake transporter, and with impaired movement when tested on a challenging beam. Our findings suggest that MPTP may trigger the neurodegenerative process by obstructing the mitochondrial function; however, striatal mitochondria in young animals may potentially rejuvenate, whereas mitochondrial dysfunction is sustained in the aged chronic MPD. Therefore, the aged chronic MPD may serve as a suitable investigative model for further elucidating the integral relationship between mitochondrial dysfunction and neurodegenerative disorder, and for assessing the therapeutic efficacy of mitochondrial protective agents as potential

  8. 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.

  9. Evaluation of a dynamic in vitro model to simulate the porcine ileal digestion of diets differing in carbohydrate composition.

    Science.gov (United States)

    Meunier, J P; Manzanilla, E G; Anguita, M; Denis, S; Pérez, J F; Gasa, J; Cardot, J-M; Garcia, F; Moll, X; Alric, M

    2008-05-01

    The aim of the study was to assess the ability of a dynamic in vitro model to determine the digestibility of OM, CP, and starch compared with a validated, static, in vitro method and in vivo ileal digestibility obtained from growing pigs fitted with a T-cannula. Five experimental diets with different carbohydrate types and level were assessed: a standard corn-based diet (ST) or the same diet with coarse ground corn (CC), 8% sugar beet pulp (BP), 10% wheat bran (WB), or 8% sugar beet pulp and 10% wheat bran (HF). In the in vivo experiment, diets CC and HF reduced (P = 0.015) ileal digestibility of OM compared with the ST diet. The inclusion of sugar beet pulp reduced (P = 0.049) ileal CP digestibility of the BP diet. This reduction was not statistically significant when sugar beet pulp was combined with the wheat bran in the HF diet. No differences were shown for in vivo starch digestibility among diets. With the static in vitro method, the OM disappearance was greater than that observed in the in vivo experiment. In this static method, the BP and HF diets reduced (P = 0.004 and < 0.001, respectively) the disappearance of the OM compared with the ST diet. The coarse grinding of corn did not alter OM digestibility but decreased (P = 0.005) the starch digestibility. The R(2) between the in vivo results and the static in vitro methods for OM and starch digestibility was 0.99 when the CC diet was not considered. The dynamic in vitro model yielded OM and CP digestibility coefficients comparable with those obtained in vivo for the ST and CC diets. However, the values were considerably affected by the incorporation of the fibrous ingredients. Diets BP, WB, and HF had decreased (P = 0.009, 0.058, and 0.004, respectively) OM digestibility compared with the ST diet. Protein digestibility was also decreased (P < 0.001, P = 0.019, and P = 0.003, respectively) with the BP, WB, and HF diets compared with the ST diet. However, digestibility was decreased to a greater extent in the

  10. A Logic Model for the Integration of Mental Health Into Chronic Disease Prevention and Health Promotion

    Directory of Open Access Journals (Sweden)

    James Lando, MD, MPH

    2006-03-01

    Full Text Available Mental illnesses such as depression or anxiety affect an individual’s ability to undertake health-promoting behaviors. Chronic diseases can have a profound impact on an individual’s mental health; in turn, mental health status affects an individual’s ability to participate in treatment and recovery. A group of mental health and public health professionals convened to develop a logic model for addressing mental health as it relates to chronic disease prevention and health promotion. The model provides details on inputs, activities, and desired outcomes, and the designers of the model welcome input from other mental health and public health practitioners.

  11. The feasibility of imaging myocardial ischemic/reperfusion injury using 99mTc-labeled duramycin in a porcine model

    International Nuclear Information System (INIS)

    When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury. Methods: The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10–15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Results: Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post-injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post-injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3

  12. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis

    International Nuclear Information System (INIS)

    Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-α signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-α (rmTNF-α) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-α (10 μg/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model

  13. 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.

  14. Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne;

    2007-01-01

    BACKGROUND: We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role...... of angiotensin II (Ang II) receptor blocker telmisartan on chronic CsA nephrotoxicity in pigs. METHODS: Fourteen Göttingen minipigs aged 12-14 months were included: pigs received either CsA 10 mg/kg/day (n = 7) or CsA 10 mg/kg/day + telmisartan 40 mg/day (n = 7) orally for 12 months. At week 0, 12...

  15. Comparison of human and porcine skin for characterization of sunscreens

    Science.gov (United States)

    Weigmann, Hans-Jürgen; Schanzer, Sabine; Patzelt, Alexa; Bahaban, Virginie; Durat, Fabienne; Sterry, Wolfram; Lademann, Jürgen

    2009-03-01

    The universal sun protection factor (USPF) characterizing sunscreen efficacy based on spectroscopically determined data, which were obtained using the tape stripping procedure. The USPF takes into account the complete ultraviolet (UV) spectral range in contrast to the classical sun protection factor (SPF). Until now, the USPF determination has been evaluated only in human skin. However, investigating new filters not yet licensed excludes in vivo investigation on human skin but requires the utilization of a suitable skin model. The penetration behavior and the protection efficacy of 10 commercial sunscreens characterized by USPF were investigated, comparing human and porcine skin. The penetration behavior found for typical UV filter substances is nearly identical for both skin types. The comparison of the USPF obtained for human and porcine skin results in a linear relation between both USPF values with a correlation factor R2=0.98. The results demonstrate the possibility for the use of porcine skin to determine the protection efficacy of sunscreens.

  16. A Biopsychosocial Model of the Development of Chronic Conduct Problems in Adolescence.

    Science.gov (United States)

    Dodge, Kenneth A.; Pettit, Gregory S.

    2003-01-01

    A biopsychosocial model of the development of adolescent chronic conduct problems is presented and supported through a review of empirical findings. The model posits that biological dispositions and sociocultural contexts place certain children at risk in early life but that life experiences with parents, peers, and social institutions increment…

  17. Gender and genetic differences in bladder smooth muscle PPAR mRNA in a porcine model of the metabolic syndrome.

    Science.gov (United States)

    Mattern, Heather M; Lloyd, Pamela G; Sturek, Michael; Hardin, Christopher D

    2007-08-01

    The metabolic syndrome and diabetes are associated with bladder dysfunction in many people. Peroxisome proliferator-activated receptors (PPARs) may play a role in the effects of the metabolic syndrome on bladder smooth muscle (BSM). The purpose of this study was to determine if there are gender and genetic differences in PPAR levels in BSM. We measured PPAR levels using quantitative PCR in BSM from male Yucatan swine and male and female Ossabaw Island swine, which is a model for the metabolic syndrome. Male Ossabaw swine had 0.732 +/- 0.111 the amount of PPAR-alpha mRNA as male Yucatan swine (P delta mRNA was 2-fold higher in male Ossabaw swine than in female Ossabaw swine, with no significant differences in PPAR-alpha levels. However, PPAR-gamma mRNA was 4.067 +/- 0.134 times higher in female Ossabaw swine than in their male counterparts (P delta and PPAR-gamma mRNA levels in male and female Ossabaw swine BSM are not only different, but may also result in gender differences in lipid metabolism in bladder smooth muscle. We conclude that PPAR profiles in BSM may contribute to the susceptibility of BSM to lipotoxicity in the metabolic syndrome. PMID:17318406

  18. 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...

  19. Pulse Oximetry: A Non-Invasive, Novel Marker for the Quality of Chest Compressions in Porcine Models of Cardiac Arrest.

    Directory of Open Access Journals (Sweden)

    Jun Xu

    Full Text Available Pulse oximetry, which noninvasively detects the blood flow of peripheral tissue, has achieved widespread clinical use. We have noticed that the better the quality of cardiopulmonary resuscitation (CPR, the better the appearance of pulse oximetry plethysmographic waveform (POP. We investigated whether the area under the curve (AUC and/or the amplitude (Amp of POP could be used to monitor the quality of CPR.Prospective, randomized controlled study.Animal experimental center in Peking Union Medical Collage Hospital, Beijing, China.Healthy 3-month-old male domestic swine.34 local pigs were enrolled in this study. After 4 minutes of untreated ventricular fibrillation, animals were randomly assigned into two resuscitation groups: a "low quality" group (with a compression depth of 3cm and a "high quality" group (with a depth of 5cm. All treatments between the two groups were identical except for the depth of chest compressions. Hemodynamic parameters [coronary perfusion pressure (CPP, partial pressure of end-tidal carbon dioxide (PETCO2] as well as AUC and Amp of POP were all collected and analyzed.There were statistical differences between the "high quality" group and the "low quality" group in AUC, Amp, CPP and PETCO2 during CPR (P<0.05. AUC, Amp and CPP were positively correlated with PETCO2, respectively (P<0.01. There was no statistical difference between the heart rate calculated according to the POP (FCPR and the frequency of mechanical CPR at the 3rd minute of CPR. The FCPR was lower than the frequency of mechanical CPR at the 6th and the 9th minute of CPR.Both the AUC and Amp of POP correlated well with CPP and PETCO2 in animal models. The frequency of POP closely matched the CPR heart rate. AUC and Amp of POP might be potential noninvasive quality monitoring markers for CPR.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Chronic Intraventricular Administration of 1-Methyl-4-Phenylpyridinium as a Progressive Model of Parkinson’s Disease

    OpenAIRE

    Sonsalla, Patricia K.; Zeevalk, Gail D.; German, Dwight C.

    2008-01-01

    Animal models of Parkinson’s disease (PD) that more closely exhibit the chronic neuropathology seen in the human condition are needed in order to reveal processes involved with progressive neurodegeneration and for testing potential interventions for retarding dopamine (DA) neuronal loss. Here we describe the recently developed chronic rat model of PD in which 1-methyl-4-phenylpyridinium ion (MPP+) is infused chronically into the lateral cerebral ventricle. We review features of this model th...

  3. 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.

  4. A truncated diphtheria toxin based recombinant porcine CTLA-4 fusion toxin.

    Science.gov (United States)

    Peraino, Jaclyn Stromp; Schenk, Marian; Zhang, Huiping; Li, Guoying; Hermanrud, Christina E; Neville, David M; Sachs, David H; Huang, Christene A; Duran-Struuck, Raimon; Wang, Zhirui

    2013-05-31

    Targeted cell therapies are possible through the generation of recombinant fusion proteins that combine a toxin, such as diphtheria toxin (DT), with an antibody or other molecule that confers specificity. Upon binding of the fusion protein to the cell of interest, the diphtheria toxin is internalized which results in protein synthesis inhibition and subsequent cell death. We have recently expressed and purified the recombinant soluble porcine CTLA-4 both with and without N-glycosylation in yeast Pichia pastoris for in vivo use in our preclinical swine model. The glycosylated and non-N-glycosylated versions of this recombinant protein each bind to a porcine CD80 expressing B-cell lymphoma line (LCL13271) with equal affinity (K(D)=13 nM). In this study we have linked each of the glycosylated and non-N-glycosylated soluble porcine CTLA-4 proteins to the truncated diphtheria toxin DT390 through genetic engineering yielding three versions of the porcine CTLA-4 fusion toxins: 1) monovalent glycosylated soluble porcine CTLA-4 fusion toxin; 2) monovalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin and 3) bivalent non-N-glycosylated soluble porcine CTLA-4 fusion toxin. Protein synthesis inhibition analysis demonstrated that while all three fusion toxins are capable of inhibiting protein synthesis in vitro, the non-N-glycosylated porcine CTLA-4 isoforms function most efficiently. Binding analysis using flow cytometry of the porcine CTLA-4 fusion toxins to LCL13271 cells also demonstrated that the non-N-glycosylated porcine CTLA-4 isoforms bind to these cells with higher affinity compared to the glycosylated fusion toxin. The monovalent non-N-glycosylated porcine CTLA-4 fusion toxin was tested in vivo. NSG (NOD/SCID IL-2 receptor γ(-)/(-)) mice were injected with porcine CD80(+) LCL13271 tumor cells. All animals succumbed to tumors and those treated with the monovalent non-N-glycosylated porcine CTLA-4 fusion toxin survived longer based on a symptomatic scoring

  5. The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

    Directory of Open Access Journals (Sweden)

    Patel Uptal D

    2011-06-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is the focus of recent national policy efforts; however, decision makers must account for multiple therapeutic options, comorbidities and complications. The objective of the Chronic Kidney Disease model is to provide guidance to decision makers. We describe this model and give an example of how it can inform clinical and policy decisions. Methods Monte Carlo simulation of CKD natural history and treatment. Health states include myocardial infarction, stroke with and without disability, congestive heart failure, CKD stages 1-5, bone disease, dialysis, transplant and death. Each cycle is 1 month. Projections account for race, age, gender, diabetes, proteinuria, hypertension, cardiac disease, and CKD stage. Treatment strategies include hypertension control, diabetes control, use of HMG-CoA reductase inhibitors, use of angiotensin converting enzyme inhibitors, nephrology specialty care, CKD screening, and a combination of these. The model architecture is flexible permitting updates as new data become available. The primary outcome is quality adjusted life years (QALYs. Secondary outcomes include health state events and CKD progression rate. Results The model was validated for GFR change/year -3.0 ± 1.9 vs. -1.7 ± 3.4 (in the AASK trial, and annual myocardial infarction and mortality rates 3.6 ± 0.9% and 1.6 ± 0.5% vs. 4.4% and 1.6% in the Go study. To illustrate the model's utility we estimated lifetime impact of a hypothetical treatment for primary prevention of vascular disease. As vascular risk declined, QALY improved but risk of dialysis increased. At baseline, 20% and 60% reduction: QALYs = 17.6, 18.2, and 19.0 and dialysis = 7.7%, 8.1%, and 10.4%, respectively. Conclusions The CKD Model is a valid, general purpose model intended as a resource to inform clinical and policy decisions improving CKD care. Its value as a tool is illustrated in our example which projects a relationship between

  6. 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...

  7. Unique Hippocampal Changes and Allodynia in a Model of Chronic Stress

    OpenAIRE

    Kim, Seong-Ho; Moon, Il Soo; Park, In-Sick

    2013-01-01

    Sustained stress can have numerous pathologic effects. There have been several animal models for chronic stress. We tried to identify the changes of pain threshold and hippocampus in a model of chronic stress. Male Sprague-Dawley rats were kept in a cage filled with 23℃ water to a height of 2.2 cm for 7 days. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer. Golgi staining was used to identify hippocampal changes. To demonstrate how long allodyni...

  8. Gender differences in a Drosophila transcriptomic model of chronic pentylenetetrazole induced behavioral deficit.

    Directory of Open Access Journals (Sweden)

    Abhay Sharma

    Full Text Available A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ, a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK, TGF-beta, JAK-STAT, Cell communication, and Dorso-Ventral axis formation pathways in downregulated genes was previously described. Of these, female genes showed enrichment only for Dorso-Ventral axis formation. Surprisingly, the ribosomal pathway was uniquely overrepresented in genes downregulated in females. Gender differences thus exist in the Drosophila model. Gender neutral, the developmental pathway Dorso-Ventral axis formation may be considered as the candidate causal pathway in chronic pentylenetetrazole induced behavioral deficit. Prior evidence of developmental mechanisms in epileptogenesis may support potential usefulness of the fly model. Given this, gender specific pathways identified here may provide a lead for further understanding brain dimorphism in neuropsychiatric disorders.

  9. The Quest to Model Chronic Traumatic Encephalopathy: A Multiple Model & Injury Paradigm Experience

    Directory of Open Access Journals (Sweden)

    Ryan C. Turner

    2015-10-01

    Full Text Available Chronic neurodegeneration following a history of neurotrauma is frequently associated with neuropsychiatric and cognitive symptoms. In order to enhance understanding about the underlying pathophysiology linking neurotrauma to neurodegeneration, a multi-model pre-clinical approach must be established to account for the different injury paradigms and pathophysiologic mechanisms. We investigated the development of tau pathology and behavioral changes using a multi-model and multi-institutional approach, comparing the pre-clinical results to tauopathy patterns seen in post-mortem human samples from athletes diagnosed with chronic traumatic encephalopathy (CTE. We utilized a scaled and validated blast-induced traumatic brain injury model in rats and a modified pneumatic closed-head impact model in mice. Tau hyperphosphorylation was evaluated by western blot and immunohistochemistry. Elevated plus maze and Morris water maze were employed to measure impulsive-like behavior and cognitive deficits respectively. Animals exposed to single blast (~50 PSI reflected peak overpressure exhibited elevated AT8 immunoreactivity in the contralateral hippocampus at 1 month compared to controls (q = 3.96, p < 0.05. Animals exposed to repeat blast (6 blasts over 2 weeks had increased AT8 (q = 8.12, p < 0.001 and AT270 (q = 4.03, p < 0.05 in the contralateral hippocampus at 1 month post-injury compared to controls. In the modified controlled closed-head impact mouse model, no significant difference in AT8 was seen at 7 days, however a significant elevation was detected at 1 month following injury in the ipsilateral hippocampus compared to control (q = 4.34, p < 0.05. Elevated plus maze data revealed that rats exposed to single blast (q = 3.53, p < 0.05 and repeat blast (q = 4.21, p < 0.05 spent more time in seconds exploring the open arms compared to controls. Morris water maze testing revealed a significant difference between groups in acquisition times on days 22

  10. 慢性咽炎模型探讨%To explore the model of chronic pharyngitis

    Institute of Scientific and Technical Information of China (English)

    涂小红; 黄玉婷; 蔡粤川; 何跃; 彭顺林

    2013-01-01

    慢性咽炎是耳鼻喉科的一种常见病,多发病,对于慢性咽炎的发病机理、临床症状及治疗等研究较多,但实验动物的选择及造模方法却很少,导师彭顺林教授所创彭氏造模法成为慢性咽炎的经典造模方法,其后的研究者们大多沿用此法。%Chronic pharyngitis is a common disease ,frequently occurring in the Department of ENT , research the pathogenesis ,clinical symptoms and treatment of chronic pharyngitis ,but few and modeling methods of the choice of the experimental animal ,Professor Peng Shunlin created the Peng's molding become chronic pharyngitis of the classical modeling methods ,the most researchers use this method .

  11. A porcine model of orthotopic left lung transplantation%猪同种异体原位左肺移植模型的建立

    Institute of Scientific and Technical Information of China (English)

    曹浩; 周文勇; 康乐; 占贞贞; 王竹林; 汪波; 丁海燕; 范慧敏; 刘中民

    2015-01-01

    目的:建立接近于人的猪同种异体左肺原位移植动物模型。方法环江香猪12只作为供体,巴马香猪12只作为受体,左侧第4肋间开胸,完成左肺原位移植。术后1、2、4、6、12 h开胸测左、右肺动脉的压力,同时取左、右肺静脉血进行血气分析,取左、右肺组织,观察含水量及病理学改变。结果动物术后均存活,随着术后时间延长,供肺静脉血氧合指数( PaO2/FiO2)下降和肺动脉压( PAP)上升,与受体正常肺比较,差异有显著性( P<0.05)。随着时间的推移,移植肺组织出现水肿、炎性细胞浸润、红细胞渗出,肺泡壁增厚明显,部分肺泡腔完全闭塞,部分肺组织实变等变化,与受体肺组织比较,含水量增加显著( P<0.05)。结论为研究肺移植缺血再灌注损伤及免疫排斥反应研究机制提供了理想的动物模型。%Objective To establish a porcine allogeneic left lung orthotopic transplantation model to closely simu-late human lung transplantation.Methods Twelve Huanjiang mini-pigs were used as donors and 12 Bama mini-pigs as recipients.The left lung orthotopic transplantation was completed by the left fourth intercostal thoracotomy.At 1 h, 2 h, 4 h, 6 h, 12 h after transplantation, the left and right pulmonary artery pressure were measured, the left and right pulmonary vein blood gas was analyzed, and samples of the left and right lung tissues were taken to determine the water content and for pathological examination.Results All animals survived, and the transplanted pulmonary vein blood PaO2/FiO2 and PAP were rised along with the prolonged postoperative time, compared with those of the recipient normal lung showing a signifi-cant difference (P<0.05).With the pass of time, there were increasing edema, inflammatory cell infiltration, RBC ooze, thickening of alveolar wall in the transplanted lung tissue, and some alveolar lumen occlusion and lung tissue

  12. 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...... and the effects of substance P and neurokinin A infusion on insulin, glucagon, somatostatin, and exocrine secretion were studied using the isolated perfused porcine pancreas with intact vagal innervation. NK-1 and NK-2 receptor antagonists were used to investigate receptor involvement. Substance P immunoreactive...

  13. 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.

  14. Cardiometabolic Effects of Chronic Hyperandrogenemia in a New Model of Postmenopausal Polycystic Ovary Syndrome.

    Science.gov (United States)

    Dalmasso, Carolina; Maranon, Rodrigo; Patil, Chetan; Bui, Elizabeth; Moulana, Mohadetheh; Zhang, Howei; Smith, Andrew; Yanes Cardozo, Licy L; Reckelhoff, Jane F

    2016-07-01

    Postmenopausal women who have had polycystic ovary syndrome (PCOS) and chronic hyperandrogenemia may be at a greater risk for cardiovascular disease than normoandrogenemic postmenopausal women. The cardiometabolic effect of chronic hyperandrogenemia in women with PCOS after menopause is unclear. The present study was performed to test the hypothesis that chronic hyperandrogenemia in aging female rats would have more deleterious effects on metabolic function, blood pressure, and renal function than in normoandrogenemic age-matched females. Female Sprague Dawley were implanted continuously, beginning at 4-5 weeks, with dihydrotestosterone (postmenopausal hyperandrogenemic female [PMHAF]) or placebo pellets (controls), and were studied at 13 months of age. Plasma DHT was 3-fold higher, and estradiol was 90% lower in PMHAF than controls. Body weights were higher; EchoMRI showed greater fat and lean mass; and computed tomography showed more sc and visceral adiposity in PMHAF, but with similar femur length compared with controls. Insulin resistance was present in PMHAF with higher plasma insulin, normal fasting blood glucose, abnormal oral glucose tolerance test, and higher nonfasting blood glucose. Blood pressure (radiotelemetry) was significantly higher and heart rate was lower, and renal function (glomerular filtration rate) was reduced by 40% in PMHAF. Thus the aging chronically hyperandrogenemic female rat is a new model of postmenopausal PCOS, which exhibits insulin resistance and visceral obesity, hypertension, and impairment in renal function. This new model provides a unique tool to study the deleterious effects of chronic androgen excess in postmenopausal females rats. PMID:27145003

  15. Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration

    OpenAIRE

    Lau, Yuen-Sum; Patki, Gaurav; Das-Panja, Kaberi; Le, Wei-dong; Ahmad, S. Omar

    2011-01-01

    The protective impact of exercise on neurodegenerative processes has not been confirmed, and the mechanisms underlying the benefit of exercise have not been determined in human Parkinson’s disease or in chronic animal disease models. This research examined the long-term neurological, behavioral, and mechanistic consequences of endurance exercise in experimental chronic parkinsonism. We used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease with ...

  16. Group Medical Visits Using an Empowerment-based Model as Treatment for Women With Chronic Pain in an Underserved Community

    OpenAIRE

    Geller, Jeffrey S.; Kulla, Jill; Shoemaker, Alena

    2015-01-01

    Background: Over the past decade, group medical visits have become more prevalent. Group medical visits may have some advantages in treating chronic illnesses such as chronic pain as they can be more patient centered. The empowerment model is a novel approach used to provide support, education, and healthy activities guided by participants. Objective: To evaluate the early stages of a chronic pain group medical visit program based on the empowerment model. Methods: This prospective cohort stu...

  17. Research Advancements in Porcine Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton's jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases. PMID:26201864

  18. Stress in adolescents with a chronically ill parent: inspiration from Rolland's Family Systems-Illness model

    NARCIS (Netherlands)

    D.S. Sieh; A.L.C. Dikkers; J.M.A. Visser-Meily; A.M. Meijer

    2012-01-01

    This article was inspired by Rolland’s Family Systems-Illness (FSI) model, aiming to predict adolescent stress as a function of parental illness type. Ninety-nine parents with a chronic medical condition, 82 partners, and 158 adolescent children (51 % girls; mean age = 15.1 years) participated in th

  19. Disease management projects and the Chronic CareModel in action: Baseline qualitative research

    NARCIS (Netherlands)

    B. Hipple-Walters (Bethany); S.A. Adams (Samantha); A.P. Nieboer (Anna); R.A. Bal (Roland)

    2012-01-01

    textabstractBackground: Disease management programs, especially those based on the Chronic Care Model (CCM),are increasingly common in the Netherlands. While disease management programs have beenwell-researched quantitatively and economically, less qualitative research has been done. Theoverall aim

  20. Pedicle Screw Fixation Study in Immature Porcine Spines to Improve Pullout Resistance during Animal Testing

    OpenAIRE

    Le Cann, Sophie; Cachon, Thibaut; Viguier, Eric; MILADI, Lotfi; Odent, Thierry; Rossi, Jean-Marie; Chabrand, Patrick

    2015-01-01

    The porcine model is frequently used during development and validation of new spinal devices, because of its likeness to the human spine. These spinal devices are frequently composed of pedicle screws with a reputation for stable fixation but which can suffer pull-outs during preclinical implantation on young animals, leading to high morbidity. With a view to identifying the best choices to optimize pedicle screw fixation in the porcine model, this study evaluates ex vivo the impact of weight...

  1. 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.

  2. Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

    OpenAIRE

    Jung, Yang-Hee; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; lee, Ju-hyun; Seo, Jee-Yeon; Lee, Seok-Yong; Jang, Choon-Gon

    2014-01-01

    Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 a...

  3. 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.

  4. One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation

    International Nuclear Information System (INIS)

    One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation

  5. Diffusion-weighted MRI and quantitative biophysical modeling of hippocampal neurite loss in chronic stress.

    Directory of Open Access Journals (Sweden)

    Peter Vestergaard-Poulsen

    Full Text Available Chronic stress has detrimental effects on physiology, learning and memory and is involved in the development of anxiety and depressive disorders. Besides changes in synaptic formation and neurogenesis, chronic stress also induces dendritic remodeling in the hippocampus, amygdala and the prefrontal cortex. Investigations of dendritic remodeling during development and treatment of stress are currently limited by the invasive nature of histological and stereological methods. Here we show that high field diffusion-weighted MRI combined with quantitative biophysical modeling of the hippocampal dendritic loss in 21 day restraint stressed rats highly correlates with former histological findings. Our study strongly indicates that diffusion-weighted MRI is sensitive to regional dendritic loss and thus a promising candidate for non-invasive studies of dendritic plasticity in chronic stress and stress-related disorders.

  6. Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model

    OpenAIRE

    Chandan Kishor; Raghvendra Raman Mishra; Saraf, Shyam K.; Mohan Kumar; Arvind K Srivastav; Gopal Nath

    2016-01-01

    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; g...

  7. Program Implementation in the Prison System: An Organizational Study of the Chronic Care Model Program

    OpenAIRE

    Robinson, Greg

    2013-01-01

    This study provides evidence of a successful implementation of a not-for-profit operational model within a public setting. The federal government placed a receiver in charge of improving health care within the California Department of Corrections and Rehabilitation. To achieve the receivership's goals, a chronic care model from the not-for-profit sector was selected and implemented to improve the delivery of health care to inmates. The data suggest that operational programs developed outsi...

  8. Diet-related chronic disease in the northeastern United States: a model-based clustering approach

    OpenAIRE

    Flynt, Abby; Daepp, Madeleine I. G.

    2015-01-01

    Background Obesity and diabetes are global public health concerns. Studies indicate a relationship between socioeconomic, demographic and environmental variables and the spatial patterns of diet-related chronic disease. In this paper, we propose a methodology using model-based clustering and variable selection to predict rates of obesity and diabetes. We test this method through an application in the northeastern United States. Methods We use model-based clustering, an unsupervised learning a...

  9. Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

    OpenAIRE

    Jennifer Louten,; Mattson, Jeanine D.; Maria-Christina Malinao; Ying Li; Claire Emson; Felix Vega; Robert L. Wardle; Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; Rene de Waal Malefyt; Maribel Beaumont

    2012-01-01

    Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The tot...

  10. Validation of two prediction models of undiagnosed chronic kidney disease in mixed-ancestry South Africans

    OpenAIRE

    Mogueo, Amelie; Echouffo-Tcheugui, Justin B; Matsha, Tandi E.; Erasmus, Rajiv T; Kengne, Andre P.

    2015-01-01

    Background Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. Methods Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as ‘estimated glomerular filtration rate (eGFR)

  11. Stochastic modelling to evaluate the economic efficiency of treatment of chronic subclinical mastitis

    OpenAIRE

    Steeneveld, W.; Hogeveen, H; Borne, van den, D Dirk; Swinkels, J.M.

    2006-01-01

    Treatment of subclinical mastitis is traditionally no common practice. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model include, amongst others, the probability of spontaneous cure, probability of the cow becoming clinically diseased, trans...

  12. Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α) and Toll-Like Receptor 4 (TLR4) Overexpression in a Porcine Model

    Science.gov (United States)

    Zhang, Zhiyong; Haimovich, Beatrice; Kwon, Young Suk; Lu, Tyler; Fyfe-Kirschner, Billie; Olweny, Ephrem Odoy

    2016-01-01

    Purpose Ischemia/reperfusion (I/R) during partial nephrectomy (PN) contributes to acute kidney injury (AKI), which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α) and toll-like receptor 4 (TLR4), within kidney tissue and peripheral blood leukocytes (PBL) in a porcine model of PN. Materials and Methods Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0), every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed. Results Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30–60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation. Conclusions In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted. PMID:27149666

  13. 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.

  14. Modelling the effects of ionizing radiation on survival of animal population: acute versus chronic exposure.

    Science.gov (United States)

    Kryshev, A I; Sazykina, T G

    2015-03-01

    The objective of the present paper was application of a model, which was originally developed to simulate chronic ionizing radiation effects in a generic isolated population, to the case of acute exposure, and comparison of the dynamic features of radiation effects on the population survival in cases of acute and chronic exposure. Two modes of exposure were considered: acute exposure (2-35 Gy) and chronic lifetime exposure with the same integrated dose. Calculations were made for a generic mice population; however, the model can be applied for other animals with proper selection of parameter values. In case of acute exposure, in the range 2-11 Gy, the population response was in two phases. During a first phase, there was a depletion in population survival; the second phase was a recovery period due to reparation of damage and biosynthesis of new biomass. Model predictions indicate that a generic mice population, living in ideal conditions, has the potential for recovery (within a mouse lifetime period) from acute exposure with dose up to 10-11 Gy, i.e., the population may recover from doses above an LD50 (6.2 Gy). Following acute doses above 14 Gy, however, the mice population went to extinction without recovery. In contrast, under chronic lifetime exposures (500 days), radiation had little effect on population survival up to integrated doses of 14-15 Gy, so the survival of a population subjected to chronic exposure was much better compared with that after an acute exposure with the same dose. Due to the effect of "wasted radiation", the integrated dose of chronic exposure could be about two times higher than acute dose, producing the same effect on survival. It is concluded that the developed generic population model including the repair of radiation damage can be applied both to acute and chronic modes of exposure; results of calculations for generic mice population are in qualitative agreement with published data on radiation effects in mice. PMID

  15. A model of hemo-immunopoietic system adaptation to chronic low and intermediate radiation doses

    International Nuclear Information System (INIS)

    In this paper radiobiological conformities to natural laws of mice's hemoimmunopoiesis systems (lines CBA and C57 Bl/6) were investigated upon chronic internal with lowering power doses of β- irradiation 90Sr and external γ-irradiation with constant power. It was shown that determinative effects of long chronic irradiation become apparent upon development of chronic radioactive effect for experimental animals were observed upon γ-irradiation with power 6 cGy/day and more or under internal with lowering power dose of β-irradiation 90Sr introduced in concentration above 1.1 c Bq/g, that is correlated with appreciations of other author's made before, concerning 'critical' level of power doses for hemopoietic system. It was shown that reduction of medium length of animals' life correlates with dis-balance into a system and between systems' links of immuno- and hemopoiesis. Physiological balance of those systems was supplied genetically by determinative systems of sanogenesis, responded for forming adaptive processes in organism. Characteristics of positive and negative inter and outward systems' links, induced by additional radiation exposure and noticeably modified constitutive regulative mechanisms being before were made more exact. A model for adaptation of hemoimmunopoiesis system to chronic radiation exposure in a rate of low and intermediate power doses was modeled. A possibility of full or part regeneration of hemopoiesis depending on power dose and kind of irradiation was experimentally substantiated. (author)

  16. 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.

  17. 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.

  18. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  19. 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.

  20. 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.

  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. 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...... infection remains to be elucidated, and may be relevant to the pathogenesis of novel diseases such as postweaning multisystemic wasting syndrome (PMWS), which may be triggered by coinfection with PPV and porcine circovirus type 2 (PCV2). To investigate whether pigs infected with PPV generate a cell...... isolated, and virus-specific lymphoproliferative responses and the cytolytic activities of cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells were examined. Cytolytic assays were performed by the chromium release method, using as targets a syngeneic porcine kidney cell line established for the...

  3. 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

    Directory of Open Access Journals (Sweden)

    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

  4. Magnetic resonance Elastography of the Lung parenchyma in an in situ porcine model with a non-invasive 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

    2011-01-01

    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 (MRE) 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 1H based MRE 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 (Pao) in 10 adult pigs. In all animals, shear stiffness was successfully quantified at four different Pao 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 Pao values of 5, 10, 15 and 20 cm H2O respectively. Shear stiffness increased with increasing Pao, in agreement with the literature. It is concluded that in an in situ porcine lung shear stiffness can be quantitated with 1H MRE using a noninvasive mechanical driver, and that it is feasible to measure the change in shear stiffness due to change in Pao. PMID:21590723

  5. Effects of Porcine Pancreatic Enzymes on the Pancreas of Hamsters. Part 2: Carcinogenesis Studies

    OpenAIRE

    Fumiaki Nozawa; Mehmet Yalniz; Murat Saruc; Jens Standop; Hiroshi Egami; Pour, Parviz M.

    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...

  6. The interferon sensitivity of selected porcine viruses.

    OpenAIRE

    Derbyshire, J. B.

    1989-01-01

    The objective of this study was to compare the sensitivity of 11 porcine viruses to the antiviral effects of porcine interferon-alpha in serum from piglets which had been infected 19 h previously with transmissible gastroenteritis virus, and of porcine interferon-beta prepared in PK-15 cells by induction with polyinosinic:polycytidylic acid, in yield reduction assays in pig kidney cells which were treated with interferon before virus challenge, and both before and after virus challenge. The m...

  7. 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...

  8. 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

    2014-01-01

    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. PMID:24410937

  9. Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome.

    Science.gov (United States)

    Bennike, Tue Bjerg; Barnaby, Omar; Steen, Hanno; Stensballe, Allan

    2015-12-01

    Synovial fluid is present in all joint cavities, and protects the articular cartilage surfaces in large by lubricating the joint, thus reducing friction. Several studies have described changes in the protein composition of synovial fluid in patients with joint disease. However, the protein concentration, content, and synovial fluid volume change dramatically during active joint diseases and inflammation, and the proteome composition of healthy synovial fluid is incompletely characterized. We performed a normative proteomics analysis of porcine synovial fluid, and report data from optimizing proteomic methods to investigate the proteome of healthy porcine synovial fluid (Bennike et al., 2014 [1]). We included an evaluation of different proteolytic sample preparation techniques, and an analysis of posttranslational modifications with a focus on glycosylation. We used pig (Sus Scrofa) as a model organism, as the porcine immune system is highly similar to human and the pig genome is sequenced. Furthermore, porcine model systems are commonly used large animal models to study several human diseases. In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935. PMID:26543887

  10. Economic evaluation in chronic pain: a systematic review and de novo flexible economic model.

    Science.gov (United States)

    Sullivan, W; Hirst, M; Beard, S; Gladwell, D; Fagnani, F; López Bastida, J; Phillips, C; Dunlop, W C N

    2016-07-01

    There is unmet need in patients suffering from chronic pain, yet innovation may be impeded by the difficulty of justifying economic value in a field beset by data limitations and methodological variability. A systematic review was conducted to identify and summarise the key areas of variability and limitations in modelling approaches in the economic evaluation of treatments for chronic pain. The results of the literature review were then used to support the development of a fully flexible open-source economic model structure, designed to test structural and data assumptions and act as a reference for future modelling practice. The key model design themes identified from the systematic review included: time horizon; titration and stabilisation; number of treatment lines; choice/ordering of treatment; and the impact of parameter uncertainty (given reliance on expert opinion). Exploratory analyses using the model to compare a hypothetical novel therapy versus morphine as first-line treatments showed cost-effectiveness results to be sensitive to structural and data assumptions. Assumptions about the treatment pathway and choice of time horizon were key model drivers. Our results suggest structural model design and data assumptions may have driven previous cost-effectiveness results and ultimately decisions based on economic value. We therefore conclude that it is vital that future economic models in chronic pain are designed to be fully transparent and hope our open-source code is useful in order to aspire to a common approach to modelling pain that includes robust sensitivity analyses to test structural and parameter uncertainty. PMID:26377997

  11. Comparable constitutive expression and activity of cytochrome P450 between the lobes of the porcine liver.

    Science.gov (United States)

    Rasmussen, Martin Krøyer; Zamaratskaia, Galia; Ekstrand, Bo

    2014-10-01

    Due to limited availability of human liver tissue for the study of cytochrome P450 (CYP450), porcine liver tissue has been suggested as an alternative source to prepare microsomes and hepatocytes. The porcine liver is made by four different lobes. The present study investigated the expression and activity of specific CYP450 isoforms in the four lobes, with the purpose to examine if one lobe of the porcine liver resembles the human more than others. Samples from the four major lobes were taken from female pigs and mRNA expression and activity of CYP1A, 2A, 2C, 2D, 2E and 3A determined. The results showed no differences in specific mRNA expression and activity of any of the investigated CYP450 isoforms. In conclusion, the study shows that all parts of the porcine liver are equally useful as model tissue. PMID:24952075

  12. The p47phox mouse knock-out model of chronic granulomatous disease

    OpenAIRE

    1995-01-01

    Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice pr...

  13. The Chronic Care Model and Diabetes Management in US Primary Care Settings: A Systematic Review

    OpenAIRE

    Stellefson, Michael; Dipnarine, Krishna; Stopka, Christine

    2013-01-01

    Introduction The Chronic Care Model (CCM) uses a systematic approach to restructuring medical care to create partnerships between health systems and communities. The objective of this study was to describe how researchers have applied CCM in US primary care settings to provide care for people who have diabetes and to describe outcomes of CCM implementation. Methods We conducted a literature review by using the Cochrane database of systematic reviews, CINAHL, and Health Source: Nursing/Academi...

  14. Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer’s disease

    OpenAIRE

    Siedlak, Sandra L.; Casadesus, Gemma; Webber, Kate M; Pappolla, Miguel A.; Atwood, Craig S.; Smith, Mark A.; Perry, George

    2009-01-01

    Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer’s, Parkinson’s and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha...

  15. Quantitative Modeling of Microbial Population Responses to Chronic Irradiation Combined with Other Stressors

    OpenAIRE

    Shuryak, Igor; Dadachova, Ekaterina

    2016-01-01

    Microbial population responses to combined effects of chronic irradiation and other stressors (chemical contaminants, other sub-optimal conditions) are important for ecosystem functioning and bioremediation in radionuclide-contaminated areas. Quantitative mathematical modeling can improve our understanding of these phenomena. To identify general patterns of microbial responses to multiple stressors in radioactive environments, we analyzed three data sets on: (1) bacteria isolated from soil co...

  16. Degeneration in Arousal Neurons in Chronic Sleep Disruption Modeling Sleep Apnea

    OpenAIRE

    Zhu, Yan; Fenik, Polina; Zhan, Guanxia; Xin, Ryan; Veasey, Sigrid C.

    2015-01-01

    Chronic sleep disruption (CSD) is a cardinal feature of sleep apnea that predicts impaired wakefulness. Despite effective treatment of apneas and sleep disruption, patients with sleep apnea may have persistent somnolence. Lasting wake disturbances in treated sleep apnea raise the possibility that CSD may induce sufficient degeneration in wake-activated neurons (WAN) to cause irreversible wake impairments. Implementing a stereological approach in a murine model of CSD, we found reduced neurona...

  17. Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol

    OpenAIRE

    Meredith, Gloria E.; Totterdell, Susan; Potashkin, Judith A.; Surmeier, D. James

    2008-01-01

    Formidable challenges for Parkinson's disease (PD) research are to understand the processes underlying nigrostriatal degeneration and how to protect the dopamine neurons. Fundamental research relies on good animal models that demonstrate the pathological hallmarks and motor deficits of PD. Using a chronic regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) in mice, dopamine cell loss exceeds 60%, extracellular glutamate is elevated, cytoplasmic inclusions are forme...

  18. An animal model of panic vulnerability with chronic disinhibition of the dorsomedial/perifornical hypothalamus

    OpenAIRE

    Johnson, Philip L.; Shekhar, Anantha

    2012-01-01

    Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium lactate infusions or hypercapnia induction. Here we review a model of panic vulnerability in rats involving chronic inhibition of GABAergic tone in the dorsomedial/ perifornical hypothalamic (DMH/PeF) region that produces enhanced anxiety and freezing responses in fearful situations, as well as a vulnerability to displaying acute p...

  19. The Biopsychosocial Model of Treatment the Patients with Inflammatory Chronic Bowel Disease

    OpenAIRE

    Rakovec-Felser, Zlatka

    2011-01-01

    We present the organised psychological group interventions for persons with inflammatory bowel disease (ulcerose colitis, Morbus Crohn). The actual bio-psychosocial model of health and illness is used to explain the situation of chronically ill patient as stressful life position and their ways of coping with such, health-related problems. Considering that numerous psychological factors can lead to insufficient illness adaptation and (non) adherence to treatment – and all those – t...

  20. Care production for tuberculosis cases:analysis according to the elements of the Chronic Care Model

    OpenAIRE

    Daiane Medeiros da Silva; Hérika Brito Gomes de Farias; Tereza Cristina Scatena Villa; Lenilde Duarte de Sá; Maria Eugênia Firmino Brunello; Jordana Almeida Nogueira

    2016-01-01

    Abstract OBJECTIVE: To analyze the care provided to tuberculosis cases in primary health care services according to the elements of the Chronic Care Model. METHOD: Cross-sectional study conducted in a capital city of the northeastern region of Brazil involving 83 Family Health Strategy professionals.A structured tool adapted to tuberculosis-related care in Brazil was applied.Analysis was based on the development of indicators with capacity to produce care varying between limited and optimum...

  1. Disease management projects and the Chronic CareModel in action: Baseline qualitative research

    OpenAIRE

    Hipple-Walters, Bethany; Adams, Samantha; Nieboer, Anna; Bal, Roland

    2012-01-01

    textabstractBackground: Disease management programs, especially those based on the Chronic Care Model (CCM),are increasingly common in the Netherlands. While disease management programs have beenwell-researched quantitatively and economically, less qualitative research has been done. Theoverall aim of the study is to explore how disease management programs are implementedwithin primary care settings in the Netherlands; this paper focuses on the early developmentand implementation stages of fi...

  2. Disease management projects and the Chronic Care Model in action: baseline qualitative research

    OpenAIRE

    Walters Bethany; Adams Samantha A; Nieboer Anna P; Bal Roland

    2012-01-01

    Abstract Background Disease management programs, especially those based on the Chronic Care Model (CCM), are increasingly common in the Netherlands. While disease management programs have been well-researched quantitatively and economically, less qualitative research has been done. The overall aim of the study is to explore how disease management programs are implemented within primary care settings in the Netherlands; this paper focuses on the early development and implementation stages of f...

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

    Science.gov (United States)

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

    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 treated with cerulein or ethanol alone. Material and methods Thirty-two male C57BL/6 mice were randomly selected, divided into four groups, and treated intraperitoneally with saline (10 ml/kg, control group), ethanol (3 g/kg; 30% v/v), cerulein (50 µg/kg), or ethanol + cerulein, for six weeks. Histopathological and immunohistochemical assays for chronic pancreatitis index along with real-time PCR assessments for mRNA levels of inflammatory cytokines and fibrogenic markers were conducted to verify the CP induction. Results The results indicated that CP index (CPI) was significantly increased in ethanol-cerulein mice compared to the saline, ethanol, and cerulein groups (p < 0.001). Interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), α-smooth muscle actin (α-SMA), and myeloperoxidase activity were also significantly greater in both cerulein and ethanol-cerulein groups than in the saline treated animals (p < 0.001). Immunohistochemical analysis revealed enhanced expression of TGF-β and α-SMA in ethanol-cerulein mice compared to the saline group. Conclusions Intraperitoneal (IP) injections of ethanol and cerulein could successfully induce CP in mice. IP injections of ethanol provide higher reproducibility compared to ethanol feeding. The model is simple, non-invasive, reproducible, and time-saving. Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing

  4. Hemodynamic and Histologic Characterization of a Swine (Sus scrofa domestica) Model of Chronic Pulmonary Arterial Hypertension

    OpenAIRE

    Rothman, Abraham; Wiencek, Robert G; Davidson, Stephanie; William N. Evans; Restrepo, Humberto; Sarukhanov, Valeri; Rivera-Begeman, Amanda; Mann, David

    2011-01-01

    The purpose of this work was to develop and characterize an aortopulmonary shunt model of chronic pulmonary hypertension in swine and provide sequential hemodynamic, angiographic, and histologic data by using an experimental endoarterial biopsy catheter. Nine Yucatan female microswine (Sus scrofa domestica) underwent surgical anastomosis of the left pulmonary artery to the descending aorta. Sequential hemodynamic, angiographic, and pulmonary vascular samples were obtained. Six pigs (mean weig...

  5. Imaging evaluation of a porcine model with acute myocardial infarction%综合影像学评价猪急性心肌梗死模型的实验研究

    Institute of Scientific and Technical Information of China (English)

    毛庆; 梁秀琳; 成益; 周学中; 刘亚平; 程亚敏

    2013-01-01

    目的:应用开胸结扎冠状动脉前降支法,探索构建中国小型猪急性心肌梗死(AMI)模型的可行性及有效性. 方法:选取中国小型猪52只,应用开胸法结扎冠状动脉左前降支第二对角支开口远端,构建AMI模型.分别于造模前、造模后3d、28 d,行超声心动图检查.造模后28 d行单电子发射型计算机断层显像(SPECT)检查、正电子发射型计算机断层显像(PET)检查,并行病理检查,评价模型的稳定性、有效性和可靠性. 结果:共39只猪成功造模.造模后28 d,左室射血分数(LVEF)明显减低,左室舒张末径(LVEDD)及左室收缩末径(LVESD)明显增大(P<0.05).SPECT提示静息及药物负荷状态下,心肌灌注缺损面积分别占左心室面积的(31.3±2.5)%和(39.3±3.8)%.PET提示心肌灌注缺损主要集中在左室局限前壁、心尖部和室间隔. 结论:应用开胸结扎冠状动脉法建立的AMI模型,效果确切可靠,可为相关研究提供可靠的动物模型.%Objective:To investigate the feasibility of a porcine model of acute myocardial infarction (AMI) by ligating distal left anterior descending artery using a midline sternotomy. Methods: Fifty-two pigs were used in this study. A porcine model of AMI was created by ligating distal left anterior descending artery using a midline sternotomy. To evaluate the cardiac function, echocardiogram was performed before, 3 days, and 28 days after modeling. To evaluate the cardiac perfusion, single photon emission computed tomography (SPECT), and positron emission tomography (PET) were performed 28 days after the procedure. Histological analysis was made using hematoxylin &. eosin stainin (HE) and fibrosis was analyzed by Masson' s trichrome. Results: A total of thirty-nine pigs were modeled successfully. Twenty-eight days after modeling, ejection fraction was significantly decreased, left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly increased

  6. A microsimulation model for the development and progression of chronic obstructive pulmonary disease.

    Science.gov (United States)

    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. PMID:26499910

  7. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

    Directory of Open Access Journals (Sweden)

    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.

  8. Application of transtheoretical model to assess the compliance of chronic periodontitis patients to periodontal therapy

    Directory of Open Access Journals (Sweden)

    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.

  9. Application of transtheoretical model to assess the compliance of chronic periodontitis patients to periodontal therapy

    Science.gov (United States)

    Emani, Shilpa; Thomas, Raison; Shah, Rucha; Mehta, Dhoom Singh

    2016-01-01

    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. PMID:27307663

  10. Renal Artery Embolization Combined With Radiofrequency Ablation in a Porcine Kidney Model: Effect of Small and Narrowly Calibrated Microparticles as Embolization Material on Coagulation Diameter, Volume, and Shape

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effect of renal artery embolization with small and narrowly calibrated microparticles on the coagulation diameter, volume, and shape of radiofrequency ablations (RFAs) in porcine kidneys. Forty-eight RFAs were performed in 24 kidneys of 12 pigs. In 6 animals, bilateral renal artery embolization was performed with small and narrowly calibrated microparticles. Upper and lower kidney poles were ablated with identical system parameters. Applying three-dimensional segmentation software, RFAs were segmented on registered 2 mm-thin macroscopic slices. Length, depth, width, volumesegmented, and volumecalculated were determined to describe the size of the RFAs. To evaluate the shape of the RFAs, depth-to-width ratio (perfect symmetry-to-lesion length was indicated by a ratio of 1), sphericity ratio (perfect sphere was indicated by a sphericity ratio of 1), eccentricity (perfect sphere was indicated by an eccentricity of 0), and circularity (perfect circle was indicated by a circularity of 1) were determined. Embolized compared with nonembolized RFAs showed significantly greater depth (23.4 ± 3.6 vs. 17.2 ± 1.8 mm; p segmented (8.6 ± 3.2 vs. 3.0 ± 0.7 ml; p calculated (8.4 ± 3.0 ml vs. 3.3 ± 1.1 ml; p < 0.001); significantly lower depth-to-width (1.17 ± 0.10 vs. 1.48 ± 0.44; p < 0.05), sphericity (1.55 ± 0.44 vs. 1.96 ± 0.43; p < 0.01), and eccentricity (0.84 ± 0.61 vs. 1.73 ± 0.91; p < 0.01) ratios; and significantly greater circularity (0.62 ± 0.14 vs. 0.45 ± 0.16; p < 0.01). Renal artery embolization with small and narrowly calibrated microparticles affected the coagulation diameter, volume, and shape of RFAs in porcine kidneys. Embolized RFAs were significantly larger and more spherical compared with nonembolized RFAs.

  11. 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 pharmaceu......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...... pharmaceutical therapy is needed, and can only be tested in a suitable animal model. The porcine model is promising and the mfERG is well validated in this model. RD was induced in 18 pigs by vitrectomy and healon injection of various concentrations. Preoperatively and 6 weeks postoperatively eight animals were...... examined by mfERG. The major component P1 was analyzed statistically. Indirect ophthalmoscopy and bilateral color fundus photography (FP) were performed. Selected animals underwent high-resolution optical coherence tomography (OCT). Examination by ophthalmoscopy and FP showed that the RDs remained detached...

  12. Development and validation of a chronic copper biotic ligand model for Ceriodaphnia dubia

    International Nuclear Information System (INIS)

    A biotic ligand model (BLM) to predict chronic Cu toxicity to Ceriodaphnia dubia was developed and tested. The effect of cationic competition, pH and natural organic matter complexation of Cu was examined to develop the model. There was no effect of cationic competition using increasing Ca and Na concentrations in our exposures. However, we did see a significant regression of decreasing toxicity (measured as the IC25; concentration at which there was a 25% inhibition of reproduction) as Mg concentration increased. However, taking into account the actual variability of the IC25 and since the relative increase in IC25 due to additional Mg was small (1.5-fold) Mg competition was not included in the model. Changes in pH had a significant effect on Cu IC25, which is consistent with proton competition as often suggested for acute BLMs. Finally, natural organic matter (NOM) was added to exposures resulting in significant decreases in toxicity. Therefore, our predictive model for chronic Cu toxicity to C. dubia includes the effect of pH and NOM complexation. The model was validated with Cu IC25 data generated in six natural surface waters collected from across Canada. Using WHAM VI, we calculated Cu speciation in each natural water and using our model, we generated 'predicted' IC25 data. We successfully predicted all Cu IC25 within a factor of 3 for the six waters used for validation

  13. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants.

    Science.gov (United States)

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    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. PMID:27589798

  14. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

    Science.gov (United States)

    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. PMID:21439399

  15. Complementary therapy in chronic wound management: a holistic caring case study and praxis model.

    Science.gov (United States)

    Popoola, Mercy Mammah

    2003-01-01

    Holistic caring consists of providing care to each aspect of a patient's life through the use of therapeutic caring and complementary or alternative healing modalities. Since nursing consists of caring for the whole person and not just the disease process, consideration of a patient's physical, emotional, social, economic, spiritual, and cultural needs is necessary in dealing with any chronic health problem such as chronic wounds. In this model case studies presentation, the purpose of this article is to discuss the importance of the holistic caring approach and the use of complementary and alternative medicine or therapeutic modalities in chronic wound management. The use or role of theory in practice will also be discussed to emphasize the holistic caring praxis model used in the holistic assessment and holistic plan of care for the cases presented. This article also presents a framework that will help wound care and holistic nurses move from simply the positivist-modernist philosophy to begin to embrace the postmodernist philosophy. PMID:12784899

  16. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    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. PMID:27029428

  17. Review of the chronic exposure pathways models in MACCS [MELCOR Accident Consequence Code System] and several other well-known probabilistic risk assessment models

    International Nuclear Information System (INIS)

    The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above

  18. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

    OpenAIRE

    Patrícia Garrido; Sandra Ribeiro; João Fernandes; Helena Vala; Petronila Rocha-Pereira; Elsa Bronze-da-Rocha; Luís Belo; Elísio Costa; Alice Santos-Silva; Flávio Reis

    2016-01-01

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue ...

  19. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    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.

  20. 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. PMID:27254279

  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. Intracoronary optical coherence tomography and histology at 1 month and 2, 3, and 4 years after implantation of everolimus-eluting bioresorbable vascular scaffolds in a porcine coronary artery model: An attempt to decipher the human optical coherence tomography images in the ABSORB trial

    OpenAIRE

    Onuma, Yosinobu; Serruys, Patrick; Perkins, Laura; Okamura, Takayuki; Gonzalo, Nieves; Garcia-Garcia, Hector; Regar, Eveline; Kamberi, Marika; Powers, Jennifer C.; Rapoza, Richard; Beusekom, Heleen; Giessen, Wim; Virmani, Renu

    2010-01-01

    textabstractBackground-: With the use of optical coherence tomography (OCT), alterations of the reflectance characteristics of everolimus-eluting bioresorbable vascular scaffold (BVS) struts have been reported in humans. In the absence of histology, the interpretation of the appearances of the struts by OCT remains speculative. We therefore report OCT findings with corresponding histology in the porcine coronary artery model immediately after and at 28 days and 2, 3, and 4 years after BVS imp...

  3. SPONTANEOUS TRANSFORMATION OF CULTURED PORCINE BONE MARROW STROMAL CELLS

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Li, Haisheng;

    -term culture are transformed into malignant cells. MATERIAL AND METHODS BMSC from 6 pigs were isolated and propagated continuously. Cell morphology was observed. Transformation properties were evaluated by means of serum dependence assay, Ki- 67 immunostaining, soft agar colony assay, karyotyping, telomerase...... was increased and TGF‚ signaling pathway was upregulated. However, telomerase activity maintained negative during culture. CONCLUSION Porcine BMSC can undergo spontaneous transformation, which provides a useful model to study the mechanisms associated with the tumorigenic potential of adult stem cells....

  4. Porcine parvovirus removal using trimer and biased hexamer peptides

    OpenAIRE

    Heldt, Caryn L.; Gurgel, Patrick V.; Jaykus, Lee-Ann; Carbonell, Ruben G.

    2011-01-01

    Assuring the microbiological safety of biological therapeutics remains an important concern. Our group has recently reported small trimeric peptides that have the ability to bind and remove a model non-enveloped virus, porcine parvovirus (PPV), from complex solutions containing human blood plasma. In an effort to improve the removal efficiency of these small peptides, we created a biased library of hexamer peptides that contain two previously reported trimeric peptides designated WRW and KYY....

  5. Disease management projects and the Chronic Care Model in action: baseline qualitative research

    Directory of Open Access Journals (Sweden)

    Walters Bethany

    2012-05-01

    Full Text Available Abstract Background Disease management programs, especially those based on the Chronic Care Model (CCM, are increasingly common in the Netherlands. While disease management programs have been well-researched quantitatively and economically, less qualitative research has been done. The overall aim of the study is to explore how disease management programs are implemented within primary care settings in the Netherlands; this paper focuses on the early development and implementation stages of five disease management programs in the primary care setting, based on interviews with project leadership teams. Methods Eleven semi-structured interviews were conducted at the five selected sites with sixteen professionals interviewed; all project directors and managers were interviewed. The interviews focused on each project’s chosen chronic illness (diabetes, eating disorders, COPD, multi-morbidity, CVRM and project plan, barriers to development and implementation, the project leaders’ action and reactions, as well as their roles and responsibilities, and disease management strategies. Analysis was inductive and interpretive, based on the content of the interviews. After analysis, the results of this research on disease management programs and the Chronic Care Model are viewed from a traveling technology framework. Results This analysis uncovered four themes that can be mapped to disease management and the Chronic Care Model: (1 changing the health care system, (2 patient-centered care, (3 technological systems and barriers, and (4 integrating projects into the larger system. Project leaders discussed the paths, both direct and indirect, for transforming the health care system to one that addresses chronic illness. Patient-centered care was highlighted as needed and a paradigm shift for many. Challenges with technological systems were pervasive. Project leaders managed the expenses of a traveling technology, including the social, financial, and

  6. Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.

    Science.gov (United States)

    Varga-Szemes, Akos; Simor, Tamas; Lenkey, Zsofia; van der Geest, Rob J; Kirschner, Robert; Toth, Levente; Brott, Brigitta C; Elgavish, Ada; Elgavish, Gabriel A

    2014-06-01

    To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure. PMID:24718787

  7. 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

    for continuous intramuscular MPTP delivery (2-24 mg MPTP/day). Six pigs served as normal controls. During 11 weeks the general behavior and motor performance of the animals were observed and scored. All animals underwent digital gait analysis preoperatively, 4 and 11 weeks postoperatively using an......-related decrease in gait velocity for the intoxicated animals. This decrease could be reversed completely with apomorphine. For dosages of 2-12 mg MPTP/day, the symptoms failed to progress from the initial state of mild Parkinsonism, and some recovery was observed. Animals receiving 18 mg/day progressed to...... moderate parkinsonism, 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...

  8. Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in a Male Rat Chronic Stress Model.

    Science.gov (United States)

    Franco, Alier J; Chen, Chun; Scullen, Tyler; Zsombok, Andrea; Salahudeen, Ahmed A; Di, Shi; Herman, James P; Tasker, Jeffrey G

    2016-06-01

    Stress activation of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by rapid glucocorticoid negative feedback. Chronic unpredictable stress animal models recapitulate certain aspects of major depression in humans, which have been attributed to impaired glucocorticoid negative feedback. We tested for an attenuated HPA sensitivity to fast glucocorticoid feedback inhibition in male rats exposed to a chronic variable stress (CVS) paradigm. In vitro, parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus recorded in slices from CVS rats showed an increase in basal excitatory synaptic inputs and a decrease in basal inhibitory synaptic inputs compared with neurons from control rats. There was no difference between control and CVS-treated rats in the rapid glucocorticoid suppression of excitatory synaptic inputs, a fast feedback mechanism. In vivo, CVS-treated rats showed an increase in ACTH secretion at baseline and after both iv CRH and acute stress and no impairment of the corticosterone suppression of the ACTH response, compared with controls. In an in vitro pituitary preparation, an increase in basal ACTH release, a small increase in CRH-induced ACTH release, and no decrement in the glucocorticoid suppression of ACTH release were seen in pituitaries from CVS rats. Thus, CVS does not suppress rapid glucocorticoid negative feedback at the hypothalamus or pituitary, but increases the synaptic excitability of paraventricular nucleus CRH neurons and the CRH sensitivity of the pituitary. Therefore, increased HPA activity in chronically stressed male rats is due to sensitization of the HPA axis, rather than to desensitization to rapid glucocorticoid feedback. PMID:27054552

  9. Neural Stem Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy

    Science.gov (United States)

    Hattiangady, Bharathi; Shetty, Ashok K.

    2016-01-01

    Neural stem cell (NSC) transplantation into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts ~30% of mesial temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs). However, to provide a comprehensive methodology involved in testing the efficacy of transplantation of NSCs in a rat model of chronic TLE, NSCs derived from the embryonic medial ganglionic eminence (MGE) are taken as an example in this article. The topics comprise description of the required materials, reagents and equipment, and protocols for expanding MGE-NSCs in culture, generating chronically epileptic rats, the intrahippocampal grafting, the post-grafting evaluation of the effects of NSC grafts on spontaneous recurrent seizures and cognitive impairments, analyses of the yield and the fate of graft-derived cells, and the effects of NSC grafts on the host hippocampus. PMID:21913169

  10. Montelukast versus Dexamethasone Treatment in a Guinea Pig Model of Chronic Pulmonary Neutrophilic Inflammation.

    Science.gov (United States)

    Abdel Kawy, Hala S

    2016-08-01

    Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours apart with or without treatment with Montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids. PMID:26751767

  11. Modeling methodology for the accurate and prompt prediction of symptomatic events in chronic diseases.

    Science.gov (United States)

    Pagán, Josué; Risco-Martín, José L; Moya, José M; Ayala, José L

    2016-08-01

    Prediction of symptomatic crises in chronic diseases allows to take decisions before the symptoms occur, such as the intake of drugs to avoid the symptoms or the activation of medical alarms. The prediction horizon is in this case an important parameter in order to fulfill the pharmacokinetics of medications, or the time response of medical services. This paper presents a study about the prediction limits of a chronic disease with symptomatic crises: the migraine. For that purpose, this work develops a methodology to build predictive migraine models and to improve these predictions beyond the limits of the initial models. The maximum prediction horizon is analyzed, and its dependency on the selected features is studied. A strategy for model selection is proposed to tackle the trade off between conservative but robust predictive models, with respect to less accurate predictions with higher horizons. The obtained results show a prediction horizon close to 40min, which is in the time range of the drug pharmacokinetics. Experiments have been performed in a realistic scenario where input data have been acquired in an ambulatory clinical study by the deployment of a non-intrusive Wireless Body Sensor Network. Our results provide an effective methodology for the selection of the future horizon in the development of prediction algorithms for diseases experiencing symptomatic crises. PMID:27260782

  12. Caring, chronicity and community: an emergent model of community health services provision for people living with chronic illness

    OpenAIRE

    Ryan, Denis

    2008-01-01

    Purpose An evaluation of an Integrated Care approach with the aim of exploring the components of the service which contributed to its functioning. Theory There is growing recognition internationally that conventional approaches to the management of chronic illness are not adequately meeting the needs of people with such conditions. This concern is also shared in Ireland and a pilot programme to provide an alternative community based approach was established in Callan, Co. Kilkennny, Ireland f...

  13. Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice.

    Science.gov (United States)

    Curtis, Lauren M; Datiles, Manuel B; Steinberg, Seth M; Mitchell, Sandra A; Bishop, Rachel J; Cowen, Edward W; Mays, Jacqueline; McCarty, John M; Kuzmina, Zoya; Pirsl, Filip; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2015-09-01

    Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist. There are no currently accepted definitions of ocular chronic graft-versus-host disease activity. The goal of this study was to identify predictive models of diagnosis and activity for use in clinical transplant practice. A total of 210 patients with moderate or severe chronic graft-versus-host disease were enrolled in a prospective, cross-sectional, observational study (clinicaltrials.gov identifier: 00092235). Experienced ophthalmologists determined presence of ocular chronic graft-versus-host disease, diagnosis and activity. Measures gathered by the transplant clinician included Schirmer's tear test and National Institutes of Health 0-3 Eye Score. Patient-reported outcome measures were the ocular subscale of the Lee Chronic Graft-versus-Host Disease Symptom Scale and Chief Eye Symptom Intensity Score. Altogether, 157 (75%) patients were diagnosed with ocular chronic graft-versus-host disease; 133 of 157 patients (85%) had active disease. In a multivariable model, the National Institutes of Health Eye Score (Pscore (P=0.027). These results support the use of selected transplant clinician- and patient-reported outcome measures for ocular chronic graft-versus-host disease screening when providing care to allogeneic hematopoietic stem cell transplantation survivors with moderate to severe chronic graft-versus-host disease. Prospective studies are needed to determine if the Lee ocular subscale demonstrates adequate responsiveness as a disease activity outcome measure. PMID:26088932

  14. 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.

  15. 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...

  16. Biomechanical comparison of lumbar spine instability between laminectomy and bilateral laminotomy for spinal stenosis syndrome – an experimental study in porcine model

    Directory of Open Access Journals (Sweden)

    Chen Lih-Huei

    2008-06-01

    Full Text Available Abstract Background The association of lumbar spine instability between laminectomy and laminotomy has been clinically studied, but the corresponding in vitro biomechanical studies have not been reported. We investigated the hypothesis that the integrity of the posterior complex (spinous process-interspinous ligament-spinous process plays an important role on the postoperative spinal stability in decompressive surgery. Methods Eight porcine lumbar spine specimens were studied. Each specimen was tested intact and after two decompression procedures. All posterior components were preserved in Group A (Intact. In Group B (Bilateral laminotomy, the inferior margin of L4 lamina and superior margin of L5 lamina were removed, but the L4–L5 supraspinous ligament was preserved. Fenestrations were made on both sides. In Group C (Laminectomy the lamina and spinous processes of lower L4 and upper L5 were removed. Ligamentum flavum and supraspinous ligament of L4–L5 were removed. A hydraulic testing machine was used to generate an increasing moment up to 8400 N-mm in flexion and extension. Intervertebral displacement at decompressive level L4–L5 was measured by extensometer Results The results indicated that, under extension motion, intervertebral displacement between the specimen in intact form and at two different decompression levels did not significantly differ (P > 0.05. However, under flexion motion, intervertebral displacement of the laminectomy specimens at decompression level L4–L5 was statistically greater than in intact or bilateral laminotomy specimens (P = 0.0000963 and P = 0.000418, respectively. No difference was found between intact and bilateral laminotomy groups. (P > 0.05. Conclusion We concluded that a lumbar spine with posterior complex integrity is less likely to develop segment instability than a lumbar spine with a destroyed anchoring point for supraspinous ligament.

  17. Interleukins in chronic liver disease: lessons learned from experimental mouse models

    Directory of Open Access Journals (Sweden)

    Hammerich L

    2014-09-01

    Full Text Available Linda Hammerich, Frank Tacke Department of Medicine III, University Hospital Aachen, Aachen, Germany Abstract: Interleukins represent a class of immunomodulatory cytokines, small intercellular signaling proteins, that are critically involved in the regulation of immune responses. They are produced in large amounts by various cell types during inflammatory reactions, and the balance of cytokines determines the outcome of an immune response. Therefore, cytokines are regarded as interesting therapeutic targets for the treatment of patients with liver diseases. Mouse models provide a good tool for in vivo studies on cytokine function, as human and mouse cytokines share many homologies. Sophisticated mouse models either mimicking distinct pathological conditions or targeting cytokines and cytokine-signaling pathways in the liver or even in distinct cellular compartments have provided enormous insight into the different functions of interleukins during hepatic inflammation. Interleukins may have pro- as well as anti-inflammatory functions in chronic liver diseases, some interleukins even both, dependent on the inflammatory stimulus, the producing and the responding cell type. IL-17, for example, promotes hepatic fibrogenesis through activation of hepatic stellate cells and facilitates development of liver cancer through recruitment of myeloid-derived suppressor cells. IL-22, on the other hand, protects from development of fibrosis or steatohepatitis. IL-12 balances T-helper (Th-1 and Th2 cell responses in infectious disease models. IL-13 and IL-33, two cytokines related to Th2 cells and innate lymphoid cells, promote fibrotic responses in the liver. IL-10 is the prototypic anti-inflammatory interleukin with tissue-protective functions during chronic liver injury and fibrogenesis. Despite its critical role for inducing the acute-phase response in the liver, IL-6 signaling is protective during fibrosis progression, but promotes hepatocellular carcinoma

  18. 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.

  19. 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...

  20. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    OpenAIRE

    Tae Young Jang; Ah-Yeoun Jung; Young Hyo Kim

    2016-01-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during ...

  1. 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......-dependent hyperpolarization-like response) was reduced in anhedonic rats (p < .001). This was associated with decreased transcription of intermediate-conductance Ca-activated K channels. CONCLUSIONS: Our findings demonstrate that depression-like symptoms are associated with reduced endothelium-dependent relaxation due to...

  2. The model of rat lipid metabolism disorder induced by chronic stress accompanying high-fat-diet

    OpenAIRE

    Shaodong Chen; Jing Li; Haihong Zhou; Manting Lin; Yihua Liu

    2011-01-01

    Abstract Objective To develop an animal model of Lipid Metabolism Disorder, which conforms to human clinical characteristic. Methods: There were 24 male Wistar rats that were randomly divided into 3 groups with 8 rats in each. They were group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat-diet). Group A was fed with normal diet, while group B and C were fed with high-fat-diet, going on for 55 days. From the 35th day, group B and C received one time of daily chroni...

  3. Differential effects of Smad3 targeting in a murine model of chronic kidney disease

    DEFF Research Database (Denmark)

    Kellenberger, Terese; Krag, Søren; Danielsen, Carl Christian;

    2013-01-01

    genes involved in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that blockade of Smad3 attenuates the development of TGF-β1-driven renal fibrosis. This was examined in vivo in a transgenic model of TGF-β1-induced chronic kidney disease with Smad3 or without Smad3 expression......Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role in transcriptional regulation of target...... in the kidney....

  4. Use of an ex-vivo porcine kidney model to compare the blood loss of different size of nephrostomy tracts%经皮肾镜术大小通道出血量的比较

    Institute of Scientific and Technical Information of China (English)

    雷华; 王德娟; 罗建斌; 邱剑光

    2011-01-01

    目的 比较经皮肾镜术大小通道出血量.方法 采用离体的生理盐水持续灌注的猪肾脏模型.在猪肾上建立穿刺通道后,先后建立16、18、22、24、30F5组通道,每组10个通道,分别测量失血量.结果 5组通道的出血量分别为(5.84±0.98)、(5.99±0.85)、(9.76±1.05)、(11.90±1.49)、(14.48±1.30) g/min,通道越大,出血量越多,差异有统计学意义(P<0.05).16 F与18F通道出血量之间比较差异无统计学意义(P>0.05).结论 在经皮肾镜手术中,通道越大,出血量越多,小通道经皮肾镜术可减少术中出血量.%Objective To compare the blood loss of different size of nephrostomy tracts in percutaneous nephrolithotomy (PCNL).Methods The model of isolated normal saline ( NS)-perfused porcine kidney was used to determine the blood loss of different size of nephrostomy tracts.By applying the technique of percutaneous nephrostomy,five groups of different size of nephrostomy tracts ( 16,18,22,24,30 F) were established on the porcine kidney gradually,with 10 tracts in every group,then the blood loss of each group was measured respectively.Results The blood loss of the five tracts ( 16,18,22,24,30 F)was (5.84±0.98),(5.99±0.85),(9.76±1.05),(11.90±1.49),(14.48±1.30) g/min,respectively.The blood loss was increased with the size of the tract diameter ( P < 0.05 ).There was no significant difference between 16 F and 18 F groups ( P > 0.05 ).Conclusion The blood loss of PCNL was increased with the size of the nephrostomy tracts.Mini-PCNL could cause less bleeding than standard-PCNL.

  5. 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

  6. 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.

  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. PMID:26335781

  8. 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...

  9. 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...

  10. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  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. PMID:26925597

  12. The Neuron-Astrocyte-Microglia Triad in a Rat Model of Chronic Cerebral Hypoperfusion: Protective Effect of Dipyridamole

    OpenAIRE

    Daniele Lana; Felicita Pedata; Maria Grazia Giovannini

    2014-01-01

    Chronic cerebral hypoperfusion during aging may cause progressive neurodegeneration as ischemic conditions persist. Proper functioning of the interplay between neurons and glia is fundamental for the functional organization of the brain. The aim of our research was to study the pathophysiological mechanisms, and particularly the derangement of the interplay between neurons and astrocytes-microglia with the formation of “triads,” in a model of chronic cerebral hypoperfusion induced by the two-...

  13. Effects of Ginseng Treatment on Neutrophil Chemiluminescence and Immunoglobulin G Subclasses in a Rat Model of Chronic Pseudomonas aeruginosa Pneumonia

    OpenAIRE

    Song, Zhijun; Kharazmi, Arsalan; Wu,Hong; Faber, Viggo; Moser, Claus; Krogh Johansen, Helle; Rygaard, Jørgen; Høiby, Niels

    1998-01-01

    Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is almost impossible to eradicate with antibiotic treatment. In the present study, the effects of treatment with the Chinese herbal medicine ginseng on blood polymorphonuclear leukocyte (PMN) chemiluminescence and serum specific antibody responses were studied in a rat model of chronic P. aeruginosa pneumonia mimicking CF. An aqueous extract of ginseng was administered by subcutaneous injection at a dosage of 25 mg...

  14. Detection of porcine circovirus type 1 in commercial porcine vaccines by loop-mediated isothermal amplification

    OpenAIRE

    Wang, Chun; Pang, Victor Fei; Jeng, Chian-Ren; LEE, Fan; Huang, Yu-Wen; Lin, Yeou-Liang; Hsiao, Shih-Hsuan; Lai, Shiow-Suey

    2011-01-01

    A loop-mediated isothermal amplification (LAMP) method with a real-time monitoring system was developed for the detection of porcine circovirus type 1 (PCV1) in commercial swine vaccines. This method was highly specific for PCV1. No cross-reaction to porcine circovirus type 2, porcine parvovirus, pseudorabies virus, classical swine fever virus, and porcine reproductive and respiratory syndrome virus was observed. The analytical sensitivity of the LAMP for PCV1 DNA was 10 copies/μl in the case...

  15. Structural Equation Modeling Highlights the Potential of Kim-1 as a Biomarker for Chronic Kidney Disease

    Science.gov (United States)

    Gardiner, Lesley; Akintola, Adebayo; Chen, Gang; Catania, Jeffrey M.; Vaidya, Vishal; Burghardt, Robert C.; Bonventre, Joseph V.; Trzeciakowski, Jerome; Parrish, Alan R.

    2012-01-01

    Background Chronic kidney disease (CKD) is a major public health problem, and despite continued research in the field, there is still a need to identify both biomarkers of risk and progression, as well as potential therapeutic targets. Structural equation modeling (SEM) is a family of statistical techniques that has been utilized in the fields of sociology and psychology for many years; however, its utilization in the biological sciences is relatively novel. SEM's ability to investigate complex relationships in an efficient, single model could be utilized to understand the progression of CKD, as well as to develop a predictive model to assess kidney status in the patient. Methods Fischer 344 rats were fed either an ad libitum diet or a calorically restricted diet, and a time-course study of kidney structure and function was performed. EQS, a SEM software package, was utilized to generate five CKD models of the Fisher 344 rat and identify relationships between measured variables and estimates of kidney damage and kidney function. Results All models identified strong relationships between a biomarker for CKD, kidney injury molecule-1 (Kim-1) and kidney damage, in the Fischer 344 rat CKD model. Models also indicate a strong relationship between age and renal damage and dysfunction. Conclusion SEM can be used to model CKD and could be useful to examine biomarkers in CKD patients. PMID:22269876

  16. An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors

    Directory of Open Access Journals (Sweden)

    Sherman Larry S

    2011-07-01

    Full Text Available Abstract Background CNS myelination disturbances commonly occur in chronic white matter lesions in neurodevelopmental and adult neurological disorders. Recent studies support that myelination failure can involve a disrupted cellular repair mechanism where oligodendrocyte (OL progenitor cells (OPCs proliferate in lesions with diffuse astrogliosis, but fail to fully differentiate to mature myelinating OLs. There are no in vitro models that reproduce these features of myelination failure. Results Forebrain coronal slices from postnatal day (P 0.5/1 rat pups were cultured for 1, 5, or 9 days in vitro (DIV. Slices rapidly exhibited diffuse astrogliosis and accumulation of the extracellular matrix glycosaminoglycan hyaluronan (HA, an inhibitor of OPC differentiation and re-myelination. At 1 DIV ~1.5% of Olig2+ OLs displayed caspase-3 activation, which increased to ~11.5% by 9 DIV. At 1 DIV the density of PDGFRα+ and PDGFRα+/Ki67+ OPCs were significantly elevated compared to 0 DIV (P P + OLs at 9 DIV compared to controls (217 ± 16 vs. 328 ± 17 cells/mm2, respectively; P = 0.0003, supporting an inhibitory role of HA in OL lineage progression in chronic lesions. Conclusions Diffuse white matter astrogliosis and early OPC proliferation with impaired OL maturation were reproduced in this model of myelination failure. This system may be used to define mechanisms of OPC maturation arrest and myelination failure related to astrogliosis and HA accumulation.

  17. 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.

  18. Biaxial tensile tests of the porcine ascending aorta.

    Science.gov (United States)

    Deplano, Valérie; Boufi, Mourad; Boiron, Olivier; Guivier-Curien, Carine; Alimi, Yves; Bertrand, Eric

    2016-07-01

    One of the aims of this work is to develop an original custom built biaxial set-up to assess mechanical behavior of soft tissues. Stretch controlled biaxial tensile tests are performed and stereoscopic digital image correlation (SDIC) is implemented to measure the 3D components of the generated displacements. Using this experimental device, the main goal is to investigate the mechanical behavior of porcine ascending aorta in the more general context of human ascending aorta pathologies. The results highlight that (i) SDIC arrangement allows accurate assessment of displacements and so stress strain curves, (ii) porcine ascending aorta has a nearly linear and anisotropic mechanical behavior until 30% of strain, (iii) porcine ascending aorta is stiffer in the circumferential direction than in the longitudinal one, (iv) the material coefficient representing the interaction between the two loading directions is thickness dependent, (v) taking into account the variability of the samples the stress values are independent of the stretch rate in the range of values from 10(-3) to 10(-1)s(-1) and finally, (vi) unlike other segments of the aorta, 4-month-old pigs ascending aorta is definitely not a relevant model to investigate the mechanical behavior of the human ascending aorta. PMID:27211783

  19. A STUDY OF ANTI - INFLAMMATORY ACTIVITY OF PLANT “TRIANTHEMA PORTULACASTRUM” IN CHRONIC MODELS OF INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Suresh. S

    2015-06-01

    Full Text Available BACKGROUND: Trianthema portulacastrum is being used in Ayurveda since centuries for its medicinal values , hence this study was done to know if it has got anti - inflammatory activity in chronic models of inflammation, MATERIALS AND METHODS: Wistar albino rats were treated with whole plant ethanolic extract of trianthema portulacastrum 100mg \\ kg orally with 2% gum acacia , as suspending agent and indomethacin 20mg \\ kg as standard. And the effects were observed in chronic model of inflammation namely, rexin pellet induced granuloma model, RESULT: This study demon - strated that trianthema portulacastrum reduced significantly the dry weight of granuloma that was formed after rexin pellet implantation, CONCLUSION: Trianthema po rtulacastrum has got significant anti - inflammatory activity in chronic models of inflammation.

  20. Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease.

    Science.gov (United States)

    Takeuchi, Yasuo; Takeuchi, Emiko; Ishida, Takashi; Onodera, Masafumi; Nakauchi, Hiromitsu; Otsu, Makoto

    2015-07-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by defective microbial killing in phagocytes. Long-term prognosis for CGD patients is generally poor, highlighting the need to develop minimally toxic, curative therapeutic approaches. We here describe the establishment of a mouse model in which X-linked CGD can be cured by allogeneic bone marrow transplantation. Using a combination of non-myeloablative-dose total body irradiation and a single injection of anti-CD40 ligand monoclonal antibody, transplantation of whole bone marrow cells achieved long-lasting mixed chimerism in X-linked CGD mice in a haploidentical transplantation setting. Stable mixed chimerism was maintained for up to 1 year even at a low range (CGD models. These results warrant future development of a simplified allogeneic hematopoietic cell transplantation regimen that would benefit CGD patients by allowing the use of haploidentical donor grafts without serious concerns of severe treatment-related toxicity. PMID:25921405

  1. 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.

  2. Psychosocial Adaptation to Chronic Illness and Disability: A Virtue Based Model.

    Science.gov (United States)

    Kim, Jeong Han; McMahon, Brian T; Hawley, Carolyn; Brickham, Dana; Gonzalez, Rene; Lee, Dong-Hun

    2016-03-01

    Purpose Psychosocial adaptation to chronic illness and disability (CID) is an area of study where a positive psychology perspective, especially the study of virtues and character strengths, can be implemented within the rehabilitation framework. A carefully developed theory to guide future interdisciplinary research is now timely. Methods A traditional literature review between philosophy and rehabilitation psychology was conducted in order to develop a virtue-based psychosocial adaptation theory, merging important perspectives from the fields of rehabilitation and positive psychology. Results The virtue-based psychosocial adaptation model (V-PAM) to CID is proposed in the present study. Conclusions The model involves five qualities or constructs: courage, practical wisdom, commitment to action, integrity and emotional transcendence. Each of these components of virtue contributes to an understanding of psychosocial adaptation. The present study addresses the implications and applications of V-PAM that will advance this understanding. PMID:26781509

  3. 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 with...... 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...

  4. Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models

    Science.gov (United States)

    Matsui, Mariko; Roche, Louise; Geroult, Sophie; Soupé-Gilbert, Marie-Estelle; Monchy, Didier; Huerre, Michel; Goarant, Cyrille

    2016-01-01

    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. PMID:27219334

  5. 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.)

  6. Micturition in rats: a chronic model for study of bladder function and effect of anesthetics.

    Science.gov (United States)

    Yaksh, T L; Durant, P A; Brent, C R

    1986-12-01

    The volume-evoked micturition reflex (VEMR) and the effects of anesthetics on the VEMR were studied in a chronic unanesthetized rat model. The bladder catheter was implanted chronically through a laparotomy and externalized percutaneously. An intrathecal (IT) catheter was implanted chronically in animals scheduled for an IT injection. By 2 days after implantation, infusion of saline (200 microliter/min) in the bladder reliably resulted in a low base-line pressure (BP) followed by a transient increase in bladder pressure, an opening of the sphincter (bladder opening pressure, BOP) corresponding to expression of urine (volume of urination, V), then a further rise in pressure (peak pressure, PP) and a subsequent return to base line. Seven days after implantation, values (means +/- SE) for BP, BOP, PP, and V were 10 +/- 0.3, 30 +/- 2, 67 +/- 6 cmH2O, and 1.0 +/- 0.1 ml, respectively. Residual volumes were reliably less than 2-4% of the expressed volume. The VEMR was reliably evoked up to 28 days after implantation. V values in unimplanted and implanted animals were not different. In implanted animals, VEMR parameters were not different during infusion or during spontaneous urination after oral fluid load. Administration of pentobarbital sodium (50 mg/kg ip), alpha-chloralose (130 mg/kg ip), ketamine (100 mg/kg im), halothane (in air 2%), and local anesthetics (2-chloroprocaine 3% or bupivacaine 0.75%, 10 microliter IT) produced a complete blockade of the VEMR and overflow incontinence at pressures significantly higher than BOP values. To compare overflow pressures and passive compliance of the bladder, unanesthetized animals were decapitated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3789199

  7. Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models.

    Science.gov (United States)

    Matsui, Mariko; Roche, Louise; Geroult, Sophie; Soupé-Gilbert, Marie-Estelle; Monchy, Didier; Huerre, Michel; Goarant, Cyrille

    2016-01-01

    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. PMID:27219334

  8. 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

  9. Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications

    Science.gov (United States)

    Chang, Chia Wei; Petrie, Tye; Clark, Alycia; Lin, Xin; Sondergaard, Claus S.; Griffiths, Leigh G.

    2016-01-01

    In this study, we investigate the translational potential of a novel combined construct using an FDA-approved decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) seeded with human or porcine mesenchymal stem cells (MSCs) for cardiovascular indications. With the emerging success of individual component in various clinical applications, the combination of SIS-ECM with MSCs could provide additional therapeutic potential compared to individual components alone for cardiovascular repair. We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes. Additionally, we evaluated the ability of porcine MSCs to modulate recipient graft-specific response towards SIS-ECM in a porcine cardiac patch in vivo model. Specifically, we determined: 1) in vitro loading-capacity of human MSCs on SIS-ECM, 2) effect of cell seeding on SIS-ECM structure, compositions and mechanical properties, 3) effect of SIS-ECM seeding on human MSC phenotypes and differentiation potential, and 4) optimal orientation and dose of porcine MSCs seeded SIS-ECM for an in vivo cardiac application. In this study, histological structure, biochemical compositions and mechanical properties of the FDA-approved SIS-ECM biomaterial were retained following MSCs repopulation in vitro. Similarly, the cellular phenotypes and differentiation potential of MSCs were preserved following seeding on SIS-ECM. In a porcine in vivo patch study, the presence of porcine MSCs on SIS-ECM significantly reduced adaptive T cell response regardless of cell dose and orientation compared to SIS-ECM alone. These findings substantiate the clinical translational potential of combined SIS-ECM seeded with MSCs as a promising therapeutic candidate for cardiac applications. PMID:27070546

  10. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J;

    2013-01-01

    Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...... model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without...... PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group (p <0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed...

  11. Characterization of an antigenically distinct porcine rotavirus.

    OpenAIRE

    Bridger, J C; Clarke, I. N.; McCrae, M A

    1982-01-01

    A porcine virus with rotavirus morphology, which was antigenically unrelated to previously described rotaviruses, is described. Particles with an outer capsid layer measured 75 nm and those lacking the outer layer were 63 nm in diameter. Particles which resembled cores were also identified. The virus was shown to be antigenically distinct from other rotaviruses as judged by immunofluorescence and immune electron microscopy, and it failed to protect piglets from challenge with porcine rotaviru...

  12. 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.

  13. Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

    International Nuclear Information System (INIS)

    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.

  14. Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium-dependent relaxants

    OpenAIRE

    Lawrence, R N; Clelland, C; Beggs, D.; Salama, F. D.; Dunn, W. R.; Wilson, V G

    1998-01-01

    The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the effects of two endothelium-dependent vasorelaxants, acetylcholine (ACh) and the Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary arter...

  15. Structure of Porcine Pancreatic Phospholipase A2 at 2.6 Å Resolution and Comparison with Bovine Phospholipase A2

    OpenAIRE

    Dijkstra, Bauke W.; Renetseder, Roland; Kalk, Kor H.; Hol, Wim G. J.; Drenth, Jan

    1983-01-01

    The previously published three-dimensional structure of porcine pancreatic prophospholipase A2 at 3 Å resolution was found to be incompatible with the structures of bovine phospholipase A2 and bovine prophospholipase A2. This was unexpected because of the very homologous amino acid sequences of these enzymes. Therefore, the crystal structure of the porcine enzyme was redetermined using molecular replacement methods with bovine phospholipase as the parent model. The structure was crystallograp...

  16. Social and economic determinants of pediatric health inequalities: the model of chronic kidney disease.

    Science.gov (United States)

    Sereni, Fabio; Edefonti, Alberto; Lepore, Marta; Agostoni, Carlo; Sandoval Diaz, Mabel; Silva Galan, Yajaira; Montini, Giovanni; Tognoni, Gianni

    2016-01-01

    Purpose of this review is to deal with priorities and strategies to significantly tackle inequalities in the management of pediatric diseases in low-middle-income countries. This issue has become a focal point of epidemiological and public health, with special reference to chronic nontransmissible diseases. We will provide our readership with an essential overview of the cultural, institutional, and political events, which have occurred over the last 20 y and which have produced the current general framework for epidemiology and public health. Then the most recent epidemiological data will be evaluated, in order to quantify the interaction between the medical components of the disease profiles and their socioeconomic determinants. Finally, a focus will be added on models of pediatric chronic kidney diseases, which are in our opinion amongst the most sensitive markers of the interplay between health and society. Collaborative, pediatrician-initiated, multicentre projects in these fields should be given priority in calls for grants supported by public agencies. The involvement of a critical mass of those working in the "fringes" of pediatric care is a final, essential mean by which significant results can be produced under the sole responsibility and research interest of centers of excellence. PMID:26466076

  17. Evaluation of protective effect of Aegle marmelos Corr. in an animal model of chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Vanphawng Lalremruta

    2012-01-01

    Full Text Available Objective: To evaluate ethanolic extract of leaves of Aegle marmelos in an experimental animal model of chronic fatigue syndrome for potential therapeutic benefit. Materials and Methods: Age/weight-matched female Wistar albino rats were grouped into five groups. (Group I- V (n = 8. Group I served as naïve control and II served as stress control. Except for group I animals, other group animals were subjected to forced swimming every day for 15 minutes to induce a state of chronic fatigue and simultaneously treated with ethanolic extract of Aegle marmelos (EEAM 150 and 250 mg/kg b.w. and Imipramine (20 mg.kg b.w., respectively. Duration of immobility, anxiety level and locomotor activity were assessed on day 1, 7, 14 and 21 followed by biochemical estimation of oxidative biomarkers at the end of the study. Results: Treatment with EEAM (150 and 250 mg/kg b.w. resulted in a statistically significant and dose dependent reduction (P <0.001 in the duration of immobility, reduction in anxiety and increase in locomotor activity. Dose dependent and significant reduction in LPO level and increase in CAT and SOD was observed in extract treated animals. Conclusion: The results are suggestive of potential protective effect of A. marmelos against experimentally induced CFS.

  18. Using Mobile Health to Support the Chronic Care Model: Developing an Institutional Initiative

    Directory of Open Access Journals (Sweden)

    Shantanu Nundy

    2012-01-01

    Full Text Available Background. Self-management support and team-based care are essential elements of the Chronic Care Model but are often limited by staff availability and reimbursement. Mobile phones are a promising platform for improving chronic care but there are few examples of successful health system implementation. Program Development. An iterative process of program design was built upon a pilot study and engaged multiple institutional stakeholders. Patients identified having a “human face” to the pilot program as essential. Stakeholders recognized the need to integrate the program with primary and specialty care but voiced concerns about competing demands on clinician time. Program Description. Nurse administrators at a university-affiliated health plan use automated text messaging to provide personalized self-management support for member patients with diabetes and facilitate care coordination with the primary care team. For example, when a patient texts a request to meet with a dietitian, a nurse-administrator coordinates with the primary care team to provide a referral. Conclusion. Our innovative program enables the existing health system to support a de novo care management program by leveraging mobile technology. The program supports self-management and team-based care in a way that we believe engages patients yet meets the limited availability of providers and needs of health plan administrators.

  19. Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain.

    Science.gov (United States)

    de Araujo, Aline Dantas; Mobli, Mehdi; Castro, Joel; Harrington, Andrea M; Vetter, Irina; Dekan, Zoltan; Muttenthaler, Markus; Wan, JingJing; Lewis, Richard J; King, Glenn F; Brierley, Stuart M; Alewood, Paul F

    2014-01-01

    Poor oral availability and susceptibility to reduction and protease degradation is a major hurdle in peptide drug development. However, drugable receptors in the gut present an attractive niche for peptide therapeutics. Here we demonstrate, in a mouse model of chronic abdominal pain, that oxytocin receptors are significantly upregulated in nociceptors innervating the colon. Correspondingly, we develop chemical strategies to engineer non-reducible and therefore more stable oxytocin analogues. Chemoselective selenide macrocyclization yields stabilized analogues equipotent to native oxytocin. Ultra-high-field nuclear magnetic resonance structural analysis of native oxytocin and the seleno-oxytocin derivatives reveals that oxytocin has a pre-organized structure in solution, in marked contrast to earlier X-ray crystallography studies. Finally, we show that these seleno-oxytocin analogues potently inhibit colonic nociceptors both in vitro and in vivo in mice with chronic visceral hypersensitivity. Our findings have potentially important implications for clinical use of oxytocin analogues and disulphide-rich peptides in general. PMID:24476666

  20. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    Science.gov (United States)

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass. PMID:25465889

  1. Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of tuberous sclerosis complex.

    Science.gov (United States)

    Cambiaghi, Marco; Cursi, Marco; Magri, Laura; Castoldi, Valerio; Comi, Giancarlo; Minicucci, Fabio; Galli, Rossella; Leocani, Letizia

    2013-04-01

    Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism, anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and its efficacy in treating epilepsy and neurological symptoms remains elusive. In a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem cells, we analyzed anxiety- and depression-like behaviour by elevated-plus maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test (TST), after chronic administration of rapamycin. In addition, spectral analysis of background EEG was performed. Rapamycin-treated mutant mice displayed a reduction in anxiety- and depression-like phenotype, as shown by the EPM/OFT and FST, respectively. These results were inline with EEG power spectra outcomes. The same effects of rapamycin were observed in wild-type mice. Notably, in heterozygous animals we did not observe any EEG and/or behavioural variation after rapamycin treatment. Together these results suggest that both TSC1 deletion and chronic rapamycin treatment might have a role in modulating behaviour and brain activity, and point out to the potential usefulness of background EEG analysis in tracking brain dysfunction in parallel with behavioural testing. PMID:23159330

  2. Optic neuritis and retinal ganglion cell loss in a chronic murine model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    KennethS.Shindler

    2011-08-01

    Full Text Available Multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE are neurodegenerative diseases with characteristic inflammatory demyelination in the central nervous system, including the optic nerve. Neuronal and axonal damage is considered to be the main cause of long-term disability in patients with MS. Neuronal loss, including retinal ganglion cell (RGC apoptosis in eyes with optic neuritis, also occurs in EAE. However, there is significant variability in the clinical course and level of neuronal damage in MS and EAE. The current studies examine the mechanisms and kinetics of RGC loss in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein to induce a chronic EAE disease. Clinical progression of EAE was scored daily and vision was assessed by optokinetic responses. At various time points, RGCs were counted and optic nerves were examined for inflammatory cell infiltration. Almost all EAE mice develop optic neuritis by day 15 post-immunization; however, RGC loss is delayed in these mice. No RGC loss is detected 25 days post-immunization, whereas RGC numbers in EAE mice significantly and progressively decrease compared to controls from 35-50 days post-immunization. The delayed time course of RGC loss is in stark contrast to that reported in relapsing EAE, as well as in rats with chronic EAE. Results suggest that different clinical disease courses of optic nerve inflammation may trigger distinct mechanisms of neuronal damage, or RGCs in different rodent strains may have variable resistance to neuronal degeneration.

  3. Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model

    Directory of Open Access Journals (Sweden)

    Shuzhen Kong

    2014-01-01

    Full Text Available Cyclothiazide (CTZ has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future.

  4. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    Science.gov (United States)

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-06-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

  5. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

    Science.gov (United States)

    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  6. Interlaboratory testing of porcine sera for antibodies to porcine circovirus type 2

    DEFF Research Database (Denmark)

    McNair, I.; Marshall, M.; McNeilly, F.; Bøtner, Anette; Ladekjær-Mikkelsen, A.S.; Vincent, I.; Herrmann, Brigitte; Sanchez, R.; Rhodes, C.

    2004-01-01

    A panel of 20 porcine sera was distributed to 5 laboratories across Europe and Canada. Each center was requested to test the sera for the presence of porcine circovirus type 2 antibodies using the routine assays, indirect immunofluorescence assay (IFA) and indirect immunoperoxidase monolayer assay...

  7. New Mouse Models to Investigate the Efficacy of Drug Combinations in Human Chronic Myeloid Leukemia.

    Science.gov (United States)

    Lin, Hanyang; Woolfson, Adrian; Jiang, Xiaoyan

    2016-01-01

    Chronic myeloid leukemia (CML) comprises a simple and effective paradigm for generating new insights into the cellular origin, pathogenesis, and treatment of many types of human cancer. In particular, mouse models of CML have greatly facilitated the understanding of the underlying molecular mechanisms and pathogenesis of this disease and have led to the identification of new drug targets that in some cases offer the possibility of functional cure. There are currently three established CML mouse models: the BCR-ABL transgenic model, the BCR-ABL retroviral transduction/transplantation model, and the xenotransplant immunodeficient model. Each has its own unique advantages and disadvantages. Depending on the question of interest, some models may be more appropriate than others. In this chapter, we describe a newly developed xenotransplant mouse model to determine the efficacy of novel therapeutic agents, either alone or in combination. The model facilitates the evaluation of the frequency of leukemic stem cells with long-term leukemia-initiating activity, a critical subcellular population that causes disease relapse and progression, through the utilization of primary CD34(+) CML stem/progenitor cells obtained from CML patients at diagnosis and prior to drug treatment. We have also investigated the effectiveness of new combination treatment strategies designed to prevent the development of leukemia in vivo using BCR-ABL (+) blast crisis cells as a model system. These types of in vivo studies are important for the prediction of individual patient responses to drug therapy, and have the potential to facilitate the design of personalized combination therapy strategies. PMID:27581149

  8. The Beltsville Human Nutrition Research Center's Porcine Immunology and Nutrition Resource Database

    Science.gov (United States)

    Several diverse genomics-based databases have developed to facilitate research with human and rodent models. Current porcine gene databases, however, lack the nutritional and immunological orientation and robust annotation to design effective molecular tools to study relevant pig models. To address ...

  9. 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; Mogensen, Poul; Doudet, Doris J; Sørensen, Jens Christian Hedemann; Bjarkam, C.R.

    2011-01-01

    stems including the SN were paraffin embedded and immunohistochemically stained for tyrosine hydroxylase (TH) and alpha-synuclein. Stereological examination of the SN showed progressive nigral neuron loss with increased MPTP dosages. Occasional neuronal staining confined to the cytoplasm and cell....../day, n=12) or acute MPTP intoxication for 11 days (24 mg MPTP/day, n=2) and 9 weeks of recovery. Four pigs served as normal controls. Animals were euthanized with intracardial pentobarbital injections, transcardially perfused with 5 L 4% paraformaldehyde and the brains removed. The striatae and brain...... membrane was observed in the SN but no neuronal inclusions. In the striatum, alpha-synuclein positive staining occurred in the acutely intoxicated animals and increased in intensity with increasing doses of chronic MPTP infusion. The 12 and 18 mg animals showed swollen TH-positive terminals in the striatum...

  10. Chronic Diarrhea

    Science.gov (United States)

    ... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

  11. Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model

    OpenAIRE

    Hasenfuss Gerd; Unsöld Bernhard; Michels Hellmuth; Raupach Tobias; Lüthje Lars; Kögler Harald; Andreas Stefan

    2009-01-01

    Abstract Background Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease. Methods Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmi...

  12. Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model

    DEFF Research Database (Denmark)

    Gerharz, E.W.; Gasser, J.A.; Mosekilde, Li.;

    2003-01-01

    differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P < 0.01). There was no hyperchloraemic metabolic acidosis or gross impairment of renal function. Hypomagnesaemia, hypocalcaemia and decreased......OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment...... significant loss of bone mass when combined with resection of the ileocaecal segment. Rarefaction of the trabecular network is confined to the metabolically highly active cancellous compartment, most likely as a consequence of intestinal malabsorption....

  13. Genetic design of pigs as experimental models in the combat between chronic diseases and healthy aging

    DEFF Research Database (Denmark)

    Bolund, Lars

    2012-01-01

    necessary. The pig is an excellent model for medical research as well as for testing of new methods and drugs for disease prevention and treatment. Its size and longevity makes it especially useful for the study of chronic disease processes that can be monitored and repeatedly biopsied for long periods with...... and without intervention. The genome of different pig breeds have been sequenced, revealing that the pig is genetically more similar to man than conventional laboratory animals - in agreement with the similarities in organ development, physiology and metabolism. Genetically designed minipigs...... (Göttingen and Yucatan) are obtained by genetic engineering of somatic cells and animal cloning by somatic cell nuclear transfer. Primary minipig fibroblasts are genetically modified in culture by transposon-based transgenesis and/or homologous recombination with AAV-transduced constructs. The designed pig...

  14. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis.

    Science.gov (United States)

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders. PMID:27251783

  15. In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia

    Science.gov (United States)

    Bruins, Maaike J; Lamers, Wouter H; Meijer, Alfred J; Soeters, Peter B; Deutz, Nicolaas E P

    2002-01-01

    During prolonged endotoxaemia, an increase in arginine catabolism may result in limiting substrate availability for nitric oxide (NO) production. These effects were quantitated in a chronically instrumented porcine endotoxaemia model. Ten days prior to the beginning of the experiments, pigs were catheterized. On day 0, pigs received a continuous infusion of endotoxin (3 μg kg−1 h−1) over 24 h and were saline resuscitated. Blood was drawn from the catheters at 0 and 24 h during primed-infusion of 15N2-arginine and P-aminohippurate to assess 15N2-arginine to 15N-citrulline conversion and plasma flow rates, respectively, across the portal-drained viscera, liver and hindquarter. During endotoxin infusion a hyperdynamic circulation with elevated heart rate, cardiac index and decreased mean arterial pressure was achieved, characteristic of the human septic condition. Endotoxin induced NO production by the portal-drained viscera and the liver. The increased NO production was quantitatively matched by an increase in arginine disposal. Nitrite/nitrate levels remained unchanged during endotoxaemia. Despite an increased arginine production from the hindquarter and an increased whole-body arginine appearance rate during endotoxin infusion, the plasma arginine concentration was lower in endotoxin-treated animals than in controls. On a whole-body level, the muscle was found to serve as a major arginine supplier and, considering the lowered arginine plasma levels, seems critical in providing arginine as precursor for NO synthesis in the splanchnic region. PMID:12466232

  16. Cross-reactivity of cell-selective CRRETAWAC peptide with human and porcine endothelial cells.

    Science.gov (United States)

    Dudash, Lynn A; Kligman, Faina L; Bastijanic, Jennifer M; Kottke-Marchant, Kandice; Marchant, Roger E

    2014-08-01

    We report on the cross-reactivity of the cell adhesive peptide CRRETAWAC between human and porcine endothelial cells (ECs). CRRETAWAC is a phage display derived peptide which has been shown to bind the α5 β1 receptor on human ECs, but does not bind platelets and thus could be incorporated into a coating for cardiovascular biomaterials that resists platelet adhesion and thrombosis, while allowing for endothelialization. To determine the cross-reactivity of the peptide, attachment and growth of human and porcine ECs on CRRETAWAC fluorosurfactant polymer (FSP) coated surfaces was explored. CRRETAWAC FSP was synthesized and characterized by mass spectrometry, NMR, and IR spectroscopy. pEC attachment and growth on CRRETAWAC FSP was similar to the positive controls, human fibronectin and RGD FSP, achieving confluence in 72 h. Initial adhesion on CRRETAWAC FSP was also similar for porcine and human ECs. Blocking with soluble CRRETAWAC peptide reduced adhesion to CRRETAWAC coated surfaces by over 50%, indicating that the pECs specifically bind CRRETAWAC peptide. With this study, we have demonstrated that CRRETAWAC peptide coated surfaces are capable of binding porcine ECs in a specific manner and supporting a confluent layer of pECs. In vitro validation of the porcine model was critical for ensuring the best chance of success for the in vivo testing of CRRETAWAC coated ePTFE vascular grafts. PMID:24123752

  17. L-Tetrahydropalmatine alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice.

    Science.gov (United States)

    Zhou, Hai-Hui; Wu, Dan-Lian; Gao, Li-Yan; Fang, Yun; Ge, Wei-Hong

    2016-05-01

    Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund's adjuvant. To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund's adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg). Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor-mediated dopaminergic transmission. PMID:26981712

  18. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model

    Science.gov (United States)

    Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P.; Leopold, Jane A.; Hajjar, Roger J.

    2014-01-01

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca2+-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  19. Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations

    Energy Technology Data Exchange (ETDEWEB)

    Alonzo, F. [Laboratory of Environmental Modelling, DEI/SECRE/LME, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache, Building 159, BP3, 13115 St-Paul-lez-Durance Cedex (France); Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)], E-mail: frederic.alonzo@irsn.fr; Hertel-Aas, T. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Gilek, M. [School of Life Sciences, Soedertoern University College, 14189 Huddinge (Sweden); Gilbin, R. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Oughton, D.H. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Garnier-Laplace, J. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)

    2008-09-15

    This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h{sup -1}). Population extinction was predicted at 43 mGy h{sup -1}. In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h{sup -1}), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.

  20. Modeled concentrations in rice and ingestion doses from chronic atmospheric releases of tritium

    International Nuclear Information System (INIS)

    The expansion of nuclear power programs in Asia has stimulated interest in the improved modeling of concentrations of tritium in rice, a staple crop grown throughout the far east. Normally, the specific activity model is used to calculate concentrations of tritium in the tissue water of edible plants to assess ingestion dose from chronic releases. However, because rice, like other grains, has much lower water content than most crops, the calculation must also account for organically bound tritium. This paper reviews ways to calculate steady-state concentrations of tritium in rice, including the methods of Canadian and US regulatory models, and the assumptions behind them. Concentrations in rice and resulting ingestion doses are compared for the various methods, and equations for calculating concentrations are recommended. The regulatory models underestimate doses received from ingestion of rice contaminated with tritium since they do not account explicitly for organically bound tritium. The importance of including organically bound tritium is illustrated in a comparison of doses from rice, leafy vegetables and milk for an Asian diet. Dose factors from tritium for these foods are estimated to be 135, 47, and 20 nSv y-1/(Bq m-3), respectively. Assuming known air concentrations, tritium concentrations in rice, calculated with the recommended equations, are uncertain by less than a factor 2 when tritium concentrations in the rice paddy water are known, and by less than a factor of 2.3 when concentrations in paddy water are unknown

  1. Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

    OpenAIRE

    Liu Chi-Ming; Chou Pesus; Shih Hui-Chuan; Tung Tao-Hsin

    2007-01-01

    Abstract Background We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model. Methods Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening. Results Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed m...

  2. Excisional wound healing is delayed in a murine model of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Akhil K Seth

    Full Text Available BACKGROUND: Approximately 15% of the United States population suffers from chronic kidney disease (CKD, often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment. METHODS: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR. RESULTS: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU and angiogenesis (CD31, with a concurrent increase in inflammation (CD45 as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS on qPCR. CONCLUSIONS: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

  3. Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

    Institute of Scientific and Technical Information of China (English)

    FANG Ya; Hein Putter

    2005-01-01

    In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or afterrelapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

  4. Ultrafast laser machining of porcine sclera

    Science.gov (United States)

    Góra, W. S.; Carter, R. M.; Dhillon, B.; Hand, D. P.; Shephard, J. D.

    2015-07-01

    The use of ultrafast lasers (pulsed lasers with pulse lengths of a few picoseconds or less) offers the possibility for minimally invasive removal of soft ophthalmic tissue. The potential for using pico- and femtosecond pulses for modification of scleral tissue has been reported elsewhere [1-6] and has resulted in the introduction of new, minimally invasive, procedures into clinical practice [3, 5-10]. Our research is focused on finding optimal parameters for picosecond laser machining of scleral tissue without introducing any unwanted collateral damage to the tissue. Experiments were carried out on hydrated porcine sclera in vitro, which has similar collagen organization, histology and water content (~70%) to human tissue. In this paper we present a 2D finite element ablation model which employs a one-step heating process. It is assumed that the incident laser radiation that is not reflected is absorbed in the tissue according to the Beer-Lambert law and transformed into heat energy. The experimental setup uses an industrial picosecond laser (TRUMPF TruMicro 5x50) with 5.9 ps pulses at 1030 nm, with pulse energies up to 125 μJ and a focused spot diameter of 35 μm. The use of a scan head allows flexibility in designing various scanning patterns. We show that picosecond pulses are capable of modifying scleral tissue without introducing collateral damage. This offers a possible route for minimally invasive sclerostomy. Many scanning patterns including single line ablation, square and circular cavity removal were tested.

  5. Characterization of porcine MMP-2 and its association with immune traits

    DEFF Research Database (Denmark)

    Huang, Honggang; Zhao, Weimin; Tang, Zhonglin;

    2009-01-01

    Matrix metalloproteinase-2 (MMP-2) plays important roles in inflammation and immunity besides its basic role in degrading and remodelling extracellular matrix (ECM). The expression of MMP-2 is up-regulated in many human as well as animal models of inflammatory and immune diseases. In this study, we...... cloned the 5'-upstream sequence, 3'-downstream sequence as well as other missed genomic sequences of porcine MMP-2, the genomic structure and the promotor sequence were analyzed and found to share high similarity with those of human MMP-2. Porcine MMP-2 was assigned to SSC6p14-p15, and closely linked to...

  6. 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.

  7. Tissue healing response following hyperthermic vapor ablation in the porcine longissimus muscle

    Science.gov (United States)

    Grantham, John T.; Grisez, Brian T.; Famoso, Justin; Hoey, Michael; Dixon, Chris; Coad, James E.

    2015-03-01

    As the use of hyperthermic ablation technologies has increased, so too has the need to understand their effects on tissue and their healing responses. This study was designed to characterize tissue injury and healing following hyperthermic vapor ablation in the in vivo porcine longissimus muscle model. The individual ablations were performed using the NxThera Vapor Delivery System (NxThera Inc., Minneapolis, MN). To assess the vapor ablation's evolution, the swine were euthanized post-treatment on Day 0, Day 3, Day 7, Day 14, Day 28, Day 45 and Day 90. Triphenyltetrazolium chloride viability staining (TTC staining) was used to macroscopically assess the extent of each vapor ablation within the tissue. The ablation associated healing responses were then histologically evaluated for acute inflammation, chronic inflammation, foreign body reaction and fibrosis. Two zones of tissue injury were initially identified in the ablations: 1) a central zone of complete coagulative necrosis and 2) an outer "transition zone" of viable and non-viable cells. The ablations initially increased in size from Day 0 to Day 7 and then progressively decreased in size though Day 45. The initial Day 3 healing changes originated in the transition zone with minimal acute and chronic inflammation. As time progressed, granulation tissue began to form by Day 7 and peaked around Day 14. Collagen formation, deposition and remodeling began in the adjacent healthy tissue by Day 28, replaced the ablation site by Day 45 and reorganized by Day 90. In conclusion, this vapor ablation technology provided a non-desiccating form of hyperthermic ablation that resulted in coagulative necrosis without a central thermally/heat-fixed tissue component, followed a classical wound healing pathway, and healed with minimal associated inflammation.

  8. Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

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    Correa-Muñoz Elsa

    2009-08-01

    Full Text Available Abstract Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i therapeutic adherence; (ii the incidence of the main chronic diseases in old age; (iii life expectancy without chronic diseases at 60 years of age; (iv disability adjusted life years lost; (v years of life lost due to premature mortality, and (vi years lived with disability. Discussion We propose that the

  9. Cytosolic caspases mediate mislocalised SOD2 depletion in an in vitro model of chronic prion infection

    Directory of Open Access Journals (Sweden)

    Layla Sinclair

    2013-07-01

    Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage markers accumulate in the brain during the course of this disease. The normal cellular substrate of the causative agent, the prion protein, is also linked with protective functions against oxidative stress. Our previous work has found that, in chronic prion infection, an apoptotic subpopulation of cells exhibit oxidative stress and the accumulation of oxidised lipid and protein aggregates with caspase recruitment. Given the likely failure of antioxidant defence mechanisms within apoptotic prion-infected cells, we aimed to investigate the role of the crucial antioxidant pathway components, superoxide dismutases (SOD 1 and 2, in an in vitro model of chronic prion infection. Increased total SOD activity, attributable to SOD1, was found in the overall population coincident with a decrease in SOD2 protein levels. When apoptotic cells were separated from the total population, the induction of SOD activity in the infected apoptotic cells was lost, with activity reduced back to levels seen in mock-infected control cells. In addition, mitochondrial superoxide production was increased and mitochondrial numbers decreased in the infected apoptotic subpopulation. Furthermore, a pan-caspase probe colocalised with SOD2 outside of mitochondria within cytosolic aggregates in infected cells and inhibition of caspase activity was able to restore cellular levels of SOD2 in the whole unseparated infected population to those of mock-infected control cells. Our results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalisation of SOD2 to cytosolic caspases, permitting its degradation. Eventually, cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.

  10. EFFECTS OF RADIX ANGELICAE SINENSIS AND SHUANGHUANGLIAN ON A RAT MODEL OF CHRONIC PSEUDOMONAS AERUGINOSA PNEUMONIA

    Institute of Scientific and Technical Information of China (English)

    H.K.Johansen; C.Moser; V.Faber; A.Khamzmi; J.Rygaard; N.Hφiby; Z.J.Song

    2000-01-01

    Objective. To study the effects of two kinds of Chinese herbal medicine, Radix angelicae sinensis(RAS) (当归)and Shuanghuanglian(SHL)(双黄连) on chronic Pseudomortas aerug/nosa(PA)lung infection in a rat model mimicking cystic fibrosis(CF).Methods. Rats were divided into RAS, SIlL and control groups. All rats were challenged intratracheally with alginate embedded PA and the trealments with herbal medicine started on the same day of challenge. The drugs were administered subcutaneously once a day for ten days and the control group was treated with sterile saline. The rats were sacrificed two weeks after challenge. Results. Significantly improved lung bacterial clearance(P <0.05, P < 0.01) and milder macroecopic lung pathology (P<0.005) were found in the two treated groups compared to the control group. In tbe SHL treated group, the neutrophil percent in the peripheral blood leukocytes(P < 0.05), the anti-PA IgG level in serum (P < 0.05), the incidence of lung abscesses(P < 0.005) and the incidence of acnte lung inflammafion(P < 0.05) were signitlcanfly lower than in the control group. The RAS treatment reduced fever(P < 0.05), decreased the incidence of lung abscesses(P <0.005) and lung mast cell number (P< 0.05), and lowered anti-PA IgG1 level in serum(P< 0.05) when compared to the control group. The anti-PA bacterial activity test in SHL was weakly positive whereas in RAS it was negative. Conclusion. The treatment with both herbal medicines could increase the resistance of the rats against PA lung infection and they therefore might be potential premising drugs for stimulation of the immtme system in CF patients with chronic PA lung infection.

  11. A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

    Science.gov (United States)

    Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K

    2014-01-01

    We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. PMID:25224310

  12. Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease

    OpenAIRE

    Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella

    2009-01-01

    Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.

  13. Assessment of a primary and tertiary care integrated management model for chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Peiro Meritxell

    2009-02-01

    Full Text Available Abstract Background The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care. This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD. The new model will be evaluated in terms of 1 improvement in the rational utilization of health-care services and 2 benefits reflected in improved health status and quality of life for patients. Methods/Design A quasi-experimental study of the effectiveness of a COPD management model called COPD PROCESS. The patients in the study cohorts will be residents of neighborhoods served by two referral hospitals in Barcelona, Spain. One area comprises the intervention group (n = 32,248 patients and the other the control group (n = 32,114 patients. The study will include pre- and post-intervention assessment 18 months after the program goes into effect. Analyses will be on two datasets: clinical and administrative data available for all patients, and clinical assessment information for a cohort of 440 patients sampled randomly from the intervention and control areas. The main endpoints will be the hospitalization rates in the two health-care areas and quality-of-life measures in the two cohorts. Discussion The COPD PROCESS model foresees the integrated multidisciplinary management of interventions at different levels of the health-care system through coordinated routine clinical practice. It will put into practice diagnostic and treatment procedures that are based on current evidence, multidisciplinary consensus, and efficient use of available resources. Care pathways in this model are defined in terms of patient characteristics, level of disease severity and the presence or absence of exacerbation. The protocol covers the full range of care from primary prevention to treatment of

  14. Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model

    Directory of Open Access Journals (Sweden)

    Schmitt Timothy

    2011-06-01

    Full Text Available Abstract Background Fully covered Self-Expanding metal stents (FCSEMS have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct. Methods Ten mini pigs underwent endoscopic placement of a FCSEMS (Wallflex, Boston Scientific. FCSEMS were kept in place for three months. At the end of the 3 months, FCSEMS were removed endoscopically. Five pigs were euthanized and their bile ducts harvested. The other five were kept alive for another month post removal. A single pathologist, created a scoring system (to determine degree of inflammation, fibrosis, and epithelial injury, examined all specimens in a blinded fashion. Results Four FCSEMS spontaneously migrated in the duodenum. On post mortem examination, mild mucosal thickness was noted in three bile duct specimens while superficial inflammation of the bile duct was noted in five animals. Histologic examination of the bile duct revealed focal acute inflammation in both groups. For the 5 animals euthanized immediately after stent removal, there was a tendency to have superficial mucosal erosion and fibrosis. In contrast, increased chronic inflammation was more commonly seen in the animals 1 month post stent removal, with all animals in this group showing moderate degrees of mononuclear inflammatory cell mucosal infiltrates. No severe inflammatory or fibrotic duct injury was observed in any of the study animals, with degree of injury graded as mild to moderate. Conclusion FCSEMS appear to induce minimal tissue overgrowth or fibrosis post placement. Ease of removability and no significant histologic injury are advantages noted with FCSEMS., however, further studies are needed to evaluate treating benign biliary strictures with FCSEMS in humans.

  15. 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.

  16. Protective effects of triptolide on retinal ganglion cells in a rat model of chronic glaucoma

    Directory of Open Access Journals (Sweden)

    Yang F

    2015-11-01

    Full Text Available Fan Yang, Dongmei Wang, Lingling Wu, Ying Li Ophthalmology Department, Peking University Third Hospital, Beijing, People’s Republic of China Purpose: To study the effects of triptolide, a Chinese herb extract, on retinal ganglion cells (RGCs in a rat model of chronic glaucoma.Methods: Eighty Wistar rats were randomly divided into triptolide group (n=40 and normal saline (NS group (n=40. Angle photocoagulation was used to establish the model of glaucoma, with right eye as laser treated eye and left eye as control eye. Triptolide group received triptolide intraperitoneally daily, while NS group received NS. Intraocular pressure (IOP, anti-CD11b immunofluorescent stain in retina and optic nerve, RGCs count with Nissel stain and microglia count with anti-CD11b immunofluorescence stain in retina flat mounts, retinal tumor necrosis factor (TNF-α mRNA detection by reverse transcription–polymerase chain reaction, and double immunofluorescent labeling with anti-TNF-α and anti-CD11b in retinal frozen section were performed.Results: Mean IOP of the laser treated eyes significantly increased 3 weeks after photocoagulation (P<0.05, with no statistical difference between the two groups (P>0.05. RGCs survival in the laser treated eyes was significantly improved in the triptolide group than the NS group (P<0.05. Microglia count in superficial retina of the laser treated eyes was significantly less in the triptolide group (30.40±4.90 than the NS group (35.06±7.59 (P<0.05. TNF-α mRNA expression in the retina of the laser treated eyes in the triptolide group decreased by 60% compared with that in the NS group (P<0.01. The double immunofluorescent labeling showed that TNF-α was mainly distributed around the microglia.Conclusion: Triptolide improved RGCs survival in this rat model of chronic glaucoma, which did not depend on IOP decrease but might be exerted by inhibiting microglia activities and reducing TNF-α secretion. Keywords: glaucoma, triptolide

  17. Effectiveness of the introduction of a Chronic Care Model-based program for type 2 diabetes in Belgium

    OpenAIRE

    De Maeseneer Jan; Vermeire Etienne; Verbeke Geert; Feyen Luc; Nobels Frank; Bastiaens Hilde; Sunaert Patricia; Willems Sara; De Sutter An

    2010-01-01

    Abstract Background During a four-year action research project (2003-2007), a program targeting all type 2 diabetes patients was implemented in a well-defined geographical region in Belgium. The implementation of the program resulted in an increase of the overall Assessment of Chronic Illness Care (ACIC) score from 1.45 in 2003 to 5.5 in 2007. The aim of the follow-up study in 2008 was to assess the effect of the implementation of Chronic Care Model (CCM) elements on the quality of diabetes c...

  18. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

    Directory of Open Access Journals (Sweden)

    Patrícia Garrido

    2015-12-01

    Full Text Available This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO therapy in a rat model of chronic kidney disease (CKD-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks high dose of rHuEPO (200 UI/kg bw/week treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  19. Coincidental detection of genomes of porcine parvoviruses and porcine circovirus type 2 infecting pigs in Japan

    OpenAIRE

    Saekhow, Prayuth; KISHIZUKA, Shingo; SANO, Natsuha; MITSUI, HIROKO; AKASAKI, Hajime; MAWATARI, Takahiro; Ikeda, Hidetoshi

    2015-01-01

    The infection status of 15 viruses in 120 pigs aged about 6 months was investigated based on tonsil specimens collected from a slaughterhouse. Only 5 species of porcine parvoviruses and porcine circovirus type 2 (PCV2) were detected at high frequencies; 67% for porcine parvovirus (PPV) (PPV-Kr or -NADL2 as the new abbreviation), 58% for PPV2 (CnP-PARV4), 39% for PPV3 (P-PARV4), 33% for PPV4 (PPV4), 55% for PBo-likeV (PBoV7) and 80% for PCV2. A phylogenetic analysis of PPV3 suggested that Japa...

  20. First identification of porcine parvovirus 6 in North America by viral metagenomic sequencing of serum from pigs infected with porcine reproductive and respiratory syndrome virus

    OpenAIRE

    Schirtzinger, Erin E.; Suddith, Andrew W.; Hause, Benjamin M.; Hesse, Richard A.

    2015-01-01

    Background Currently, eight species in four genera of parvovirus have been described that infect swine. These include ungulate protoparvovirus 1 (classical porcine parvovirus, PPV), ungulate tetraparvovirus 2 (PPV3), ungulate tetraparvovirus 3 (which includes PPV2, porcine hokovirus, porcine partetravirus and porcine PARV4), ungulate copiparvovirus 2 (which includes PPV4 and PPV5), ungulate bocaparvovirus 2 (which includes porcine bocavirus 1, 2 and 6), ungulate bocaparvovirus 3 (porcine boca...

  1. PROVANN: Model System for Chronic Exposure of Larval and Adult Fish to Releases from Offshore Petroleum Platforms

    International Nuclear Information System (INIS)

    Produced water from offshore oil and gas production platforms contains a variety of hydrocarbons, heavy metals, and production chemicals. Vertical and horizontal mixing generally brings concentrations in discharge plumes below level associated with acute effects within 500 or 1000 m of the source. Chronic effects outside this region remain a potential problem. The purpose of PROVANN, the system of models described in this paper, is to assess the potential for chronic effects from produced water. The preliminary focus is on potential bioaccumulation and boimagnification of produced water constituents in the marine food web. Other possible types of chronic effects, such as reduced fecundity, or pheromone response interference, can also be assessed to the extent that such effects may be correlated with exposure. PROVANN simulates 3-dimensional transport, dilution, and degradation of chemicals released into the water, from one or more simultaneous sources. 8 refs., 10 figs., 3 tabs

  2. Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease

    Science.gov (United States)

    Cao, Jian; Hao, Wei-Jun; Gao, Ling-Gen; Chen, Tian-Meng; Liu, Lin; Sun, Yu-Fa; Hu, Guo-Liang; Hu, Yi-Xin; Fan, Li

    2016-01-01

    Background Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods Elderly patients (n = 1130) with stable chronic coronary heart disease who were taking aspirin (75 mg) for > 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer–Lemeshow (HL) test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model. Results Seven risk factors were included in our risk score. They were serum creatinine (> 110 μmol/L, score of 1); fasting blood glucose (> 7.0 mmol/L, score of 1); hyperlipidemia (score of 1); number of coronary arteries (2 branches, score of 2; ≥ 3 branches, score of 4); body mass index (20–25 kg/m2, score of 2; > 25 kg/m2, score of 4); percutaneous coronary intervention (score of 2); and smoking (score of 3). The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70. Conclusions We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy. PMID:27594876

  3. Effects of dietary fruits, vegetables and a herbal tea on the in vitro transport of cimetidine: comparing the Caco-2 model with porcine jejunum tissue

    OpenAIRE

    Tarirai, Clemence; Hamman, Josias H.; Alvaro M. Viljoen

    2012-01-01

    Context: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. Objective: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. Materials and Methods: Bi-directional transport of cimetidine was m...

  4. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  5. Influence of porcine circovirus type 2 vaccination on the probability and severity of pneumonia detected postmortem

    OpenAIRE

    Raith, J; Kuchling, S.; Schleicher, C; Schobesberger, H.; Köfer, J.

    2014-01-01

    To evaluate the influence of porcine circovirus type 2 vaccination (PCV-2) on the probability and severity of pneumonia, postmortem findings of 247,505 pigs slaughtered between 2008 and 2011 were analysed by applying a cumulative link mixed model. Three major effects could be observed: (1) PCV-2 vaccination significantly (P

  6. Spatial distribution of transgenic protein after gene electrotransfer to porcine muscle

    DEFF Research Database (Denmark)

    Spanggaard, Iben; Corydon, Thomas Juhl; Hojman, Pernille;

    2012-01-01

    electrotransfer to muscle in a large animal model has not yet been investigated. In this study, 17 different doses of plasmid DNA (1-1500 μg firefly luciferase pCMV-Luc) were delivered in vivo to porcine gluteal muscle using electroporation. Forty-eight hours post treatment several biopsies were obtained from...

  7. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    Science.gov (United States)

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  8. Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration

    Directory of Open Access Journals (Sweden)

    Lau Yuen-Sum

    2009-01-01

    Full Text Available Abstract Background Animal models of Parkinson's disease have been widely used for investigating the mechanisms of neurodegenerative process and for discovering alternative strategies for treating the disease. Following 10 injections with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg and probenecid (250 mg/kg over 5 weeks in mice, we have established and characterized a chronic mouse model of Parkinson's disease (MPD, which displays severe long-term neurological and pathological defects resembling that of the human Parkinson's disease in the advanced stage. The behavioral manifestations in this chronic mouse model of Parkinson's syndrome remain uninvestigated. The health benefit of exercise in aging and in neurodegenerative disorders including the Parkinson's disease has been implicated; however, clinical and laboratory studies in this area are limited. In this research with the chronic MPD, we first conducted a series of behavioral tests and then investigated the impact of endurance exercise on the identified Parkinsonian behavioral deficits. Results We report here that the severe chronic MPD mice showed significant deficits in their gait pattern consistency and in learning the cued version of the Morris water maze. Their performances on the challenging beam and walking grid were considerably attenuated suggesting the lack of balance and motor coordination. Furthermore, their spontaneous and amphetamine-stimulated locomotor activities in the open field were significantly suppressed. The behavioral deficits in the chronic MPD lasted for at least 8 weeks after MPTP/probenecid treatment. When the chronic MPD mice were exercise-trained on a motorized treadmill 1 week before, 5 weeks during, and 8–12 weeks after MPTP/probenecid treatment, the behavioral deficits in gait pattern, spontaneous ambulatory movement, and balance performance were reversed; whereas neuronal loss and impairment in cognitive skill, motor coordination, and

  9. Neuroprotective Effect of Compound Anisodine in a Mouse Model with Chronic Ocular Hypertension

    Institute of Scientific and Technical Information of China (English)

    Wen-Dong Liu; Lan-Lan Chen; Ce-Ying Shen; Li-Bin Jiang

    2015-01-01

    Background:Compound anisodine (CA) is a compound preparation made from hydrobromide anisodine and procaine hydrochloride.The former is an M-choline receptor blocker with the function of regulating the vegetative nervous system,improving microcirculation,and so on.The latter is an antioxidant with the activities ofneuroprotection.This study aimed to investigate the potential neuroprotection of CA,which affects the degeneration of the retinal ganglion cells (RGCs) in an animal model with chronic ocular hypertension.Methods:Female C57BL/6J mice (n =24) were divided randomly into four groups:Normal control group without any treatment (Group A,n =6);CA control group with feeding the CA solution (Group B,n =6);microbeads (MBs) control group with injecting MB into the anterior chamber (Group C,n =6);CA study group with MB injection and with feeding the CA solution (Group D,n =6).Intraocular pressure (IOP) was measured every 3 days after MB injection.At the 21st day,neurons were retrograde-labeled by Fluoro-Gold (FG).Animals were sacrificed on the 27th day.Retinal flat mounts were stained immunohistologically by β-Ⅲ-tubulin.FG-retrograde-labeled RGCs,β-Ⅲ-tubulin-positive RGCs,and β-Ⅲ-tubulin-positive nerve fibers were quantified.Results:Mice of Groups C and D expressed the incidence of consistent IOP elevation,which is above the IOP level of Group A with the normal one.There is no significant difference in IOP between Groups A and B (P > 0.05).On the 27th day,there were distinct loss in stained RGCs and nerve fibers from Groups C and D compared with Group A (all P < 0.00l).The quantity was significantly higher in Group D as compared to Group C (all P < 0.00l) but lower than Group A (all P < 0.001).There was no significant difference in the quantity of RGCs and nerve fibers between Groups A and B (all P > 0.05).Conclusions:These findings suggest that CA plays an importantly neuroprotective role on RGCs in a mouse model with chronic ocular hypertension.

  10. Modelling population-level consequences of chronic external gamma irradiation in aquatic invertebrates under laboratory conditions

    International Nuclear Information System (INIS)

    We modelled population-level consequences of chronic external gamma irradiation in aquatic invertebrates under laboratory conditions. We used Leslie matrices to combine life-history characteristics (duration of life stages, survival and fecundity rates) and dose rate-response curves for hatching, survival and reproduction fitted on effect data from the FREDERICA database. Changes in net reproductive rate R0 (offspring per individual) and asymptotic population growth rate λ (dimensionless) were calculated over a range of dose rates in two marine polychaetes (Neanthes arenaceodentata and Ophryotrocha diadema) and a freshwater gastropod (Physa heterostropha). Sensitivities in R0 and λ to changes in life-history traits were analysed in each species. Results showed that fecundity has the strongest influence on R0. A delay in age at first reproduction is most critical for λ independent of the species. Fast growing species were proportionally more sensitive to changes in individual endpoints than slow growing species. Reduction of 10% in population λ were predicted at dose rates of 6918, 5012 and 74,131 μGy·h−1 in N. arenaceodentata, O. diadema and P. heterostropha respectively, resulting from a combination of strong effects on several individual endpoints in each species. These observations made 10%-reduction in λ a poor criterion for population protection. The lowest significant changes in R0 and λ were respectively predicted at a same dose rate of 1412 μGy h−1 in N. arenaceodentata, at 760 and 716 μGy h−1 in O. diadema and at 12,767 and 13,759 μGy h−1 in P. heterostropha. These values resulted from a combination of slight but significant changes in several measured endpoints and were lower than effective dose rates calculated for the individual level in O. diadema and P. heterostropha. The relevance of the experimental dataset (external irradiation rather than contamination, exposure over one generation only, effects on survival and reproduction only

  11. Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration

    OpenAIRE

    Lau Yuen-Sum; Kurz Max J; Pothakos Konstantinos

    2009-01-01

    Abstract Background Animal models of Parkinson's disease have been widely used for investigating the mechanisms of neurodegenerative process and for discovering alternative strategies for treating the disease. Following 10 injections with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg) and probenecid (250 mg/kg) over 5 weeks in mice, we have established and characterized a chronic mouse model of Parkinson's disease (MPD), which displays severe long-term neurological and patholog...

  12. Development of a Chronic Kidney Disease Model in C57BL/6 Mice with Relevance to Human Pathology

    OpenAIRE

    Huang, Linghong; Scarpellini, Alessandra; Funck, Muriel; Verderio, Elisabetta A. M.; Johnson, Timothy S.

    2013-01-01

    Background Genetically modified mice are used to investigate disease and assess potential interventions. However, research into kidney fibrosis is hampered by a lack of models of chronic kidney disease (CKD) in mice. Recently, aristolochic acid nephropathy (AAN), characterised by severe tubulointerstitial fibrosis, has been identified as a cause of end stage kidney disease and proposed as a model of CKD. Published studies have used various dosing regimens, species and strains, with variable o...

  13. Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease

    OpenAIRE

    Siouta, Naouma; Beek, K.; van der Eerden, M. E.; Preston, N.; Hasselaar, J.G.; Hughes, S; GARRALDA, E.; Centeno, C. (Carlos); Csikos, A.; Groot, M. de; Radbruch, L.; Payne, S; Menten, J.

    2016-01-01

    Background Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of futu...

  14. Validation of Ten Noninvasive Diagnostic Models for Prediction of Liver Fibrosis in Patients with Chronic Hepatitis B

    OpenAIRE

    Cheng, Jieyao; Hou, Jinlin; Ding, Huiguo; Chen, Guofeng; Xie, Qing; Wang, Yuming; Zeng, Minde; Ou, Xiaojuan; Ma, Hong; Jia, Jidong

    2015-01-01

    Background and Aims Noninvasive models have been developed for fibrosis assessment in patients with chronic hepatitis B. However, the sensitivity, specificity and diagnostic accuracy in evaluating liver fibrosis of these methods have not been validated and compared in the same group of patients. The aim of this study was to verify the diagnostic performance and reproducibility of ten reported noninvasive models in a large cohort of Asian CHB patients. Methods The diagnostic performance of ten...

  15. The Use of Amnion-Derived Cellular Cytokine Solution to Improve Healing in Acute and Chronic Wound Models

    OpenAIRE

    Franz, Michael G.; Payne, Wyatt G.; Xing, Liyu; Naidu, D. K; Salas, R. E; Marshall, Vivienne S.; Trumpower, C. J; Smith, Charlotte A; Steed, David L.; Robson, M. C.

    2008-01-01

    Objective: Growth factors demonstrate mixed results improving wound healing. Amnion-derived multipotent cells release physiologic levels of growth factors and tissue inhibitors of metalloproteinases. This solution was tested in models of acute and chronic wound healing. Methods: Acute model: Sprague-Dawley rats underwent laparotomy incisions. The midline fascia was primed with phosphate-buffered saline, unconditioned media, or amnion-derived cellular cytokine suspension prior to incision. Bre...

  16. Immortalization of porcine placental trophoblast cells through reconstitution of telomerase activity.

    Science.gov (United States)

    Zhang, Hongling; Huang, Yong; Wang, Lili; Yu, Tingting; Wang, Zengguo; Chang, Lingling; Zhao, Xiaomin; Luo, Xiaomao; Zhang, Liang; Tong, Dewen

    2016-05-01

    Placental trophoblast cells (PTCs) play a critical role in histotrophic nutrient absorption, gaseous exchange, endocrine activities, and barrier function between the maternal and fetal systems. Establishment of immortalized porcine PTCs will help us to investigate the potential effects of different viruses on porcine trophoblast. In the present study, primary porcine PTCs were isolated from healthy gilts at Day 30 to Day 50 of gestation through collagenase digestion, percoll gradient centrifugation, and anti-CD9 immunomagnetic negative selection. To provide stable and long lifespan cells, primary PTCs were transfected with human telomerase reverse transcriptase (hTERT) gene. One porcine placental trophoblast cell line, named as hTERT-PTCs, was chosen for characterization. Human telomerase reverse transcriptase-PTCs achieved an extended replicative lifespan without exhibiting any neoplastic transformation signs in vivo or in vitro. The morphologic and key physiological characteristics of the immortalized PTCs were similar to primary PTCs. The immortalized PTCs retained original cell polarity and normal karyotype, expressed trophoblast-specific marker cytokeratin 7 and E-cadherin but did not express vimentin and major histocompatibility complex class I antigens as well as primary PTCs. Human telomerase reverse transcriptase-PTCs secreted low levels of chorionic gonadotrophin β-subunit and placental lactogen that were coincident with primary PTCs. Taken together, our results demonstrated that the porcine PTCs could be immortalized through reconstitution of telomerase activity. The immortalized PTCs maintained its original characteristics and can be used as a model cells line to study the pathologic changes of porcine placental trophoblast in viruses infectious diseases. PMID:26850465

  17. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Bai Han

    2012-08-01

    Full Text Available Abstract Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID, on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

  18. Simplified cryopreservation of porcine cloned blastocysts

    DEFF Research Database (Denmark)

    Du, Yutao; Zhang, Yunhai; Li, Juan;

    2007-01-01

    )â€"handmade cloning (HMC)â€"to establish a simplified and efficient cryopreservation system for porcine cloned embryos. In Experiment 1, zonae pellucidae of oocytes were partially digested with pronase, followed by centrifugation to polarize lipid particles. Ninety percent (173/192) oocytes were successfully......). Our results prove that porcine embryos produced from delipated oocytes by PA or HMC can be cryopreserved effectively by ultrarapid vitrification. Further experiments are required to assess the in vivo developmental competence of the cloned-vitrified embryos  ...

  19. Porcine Circovirus Diseases: A review of PMWS

    DEFF Research Database (Denmark)

    Baekbo, P.; Kristensen, C. S.; Larsen, L. E.

    2012-01-01

    This article is a review on post‐weaning multisystemic wasting syndrome (PMWS), the first described disease among the porcine circovirus diseases (PCVD). Post‐weaning multisystemic wasting syndrome has, since its appearance in Canada in 1991, been seen in all major pig producing countries. To...... vaccines against Porcine Circo Virus type 2 have been coming on the market and many studies have shown great benefits of these to control PMWS. Today, sow vaccines as well as piglet vaccines are available in most countries. An extensive meta‐analysis of many of the vaccines has shown a comparable good...

  20. Role of bile acids, prostaglandins and COX inhibitors in chronic esophagitis in a mouse model

    Institute of Scientific and Technical Information of China (English)

    C Poplawski; D Sosnowski; A Szaflarska-Poplawska; J Sarosiek; R McCallum; Z Bartuzi

    2006-01-01

    33 %). In HCl/P/BA/INDO group the esophagitis surface was larger than that in not treated group (33%). In HCL/P group the surface of esophagus with ulceration was significantly larger (10-fold) than that in HCl/P/BA group. The PGE2 concentration was significantly higher in HCl/P group than in HCl/P/BA group.The PGE2 concentration in lower part of esophagus was also significantly higher in middle than those in HCl and HCl/P/BA groups. In upper part of esophagus the PGE2 concentration was significantly higher in HCl/P/BA group than that in group treated with indometacine (46%). We also observed higher PGE2 concentration in middle part of esophagus in HCl/P/BA group than those in group treated with indometacine and in group treated with indometacin and NS-398 (by 52% and 43% respectively).CONCLUSION: Pepsin is the pivotal factor in the development of chronic esophageal injury. Bile acids diminish chronic esophageal injury induced by HCl/P, indicating its potential negative impact on pepsin proteolytic potential,pivotal for mucosal injury in low pH. The role of selective COX inhibitors is still unclear, and needs more investigations. This novel chronic experimental esophagitis is an excellent model for further study on the role of cytokines in genetically modified animals.