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Sample records for porcine experimental model

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

  5. A fiber reinforced poroelastic model of nanoindentation of porcine costal cartilage: a combined experimental and finite element approach.

    PubMed

    Gupta, Shikha; Lin, Jeremy; Ashby, Paul; Pruitt, Lisa

    2009-08-01

    Nanoindentation has shown promise as a mechanical characterization tool for orthopaedic biomaterials since it can probe the properties of small, heterogeneous, irregularly shaped tissue volumes in physiological environments. However, the majority of nanoindentation analyses have been limited to the determination of linear elastic and viscoelastic properties. Since biomaterials possess complex nonlinear, hydrated, time-dependent constitutive behavior, the objective of the present study is to explore the ability of nanoindentation to determine physiologically relevant material properties using a fibril reinforced poroelastic (FRPE) model. A further goal is to ascertain the sensitivity of nanoindentation load-displacement curves to different FRPE parameters, including the elastic properties of the nonfibrillar matrix, the composition and distribution of fibers, and nonlinearity in the fluid permeability. Porcine costal cartilage specimens are experimentally tested with nanoindentation load relaxation experiments at two different loading depths and loading rates. The FRPE material properties are extracted from comparisons to finite element simulations. The study demonstrates the behavior of the model in nanoindentation is distinct from bulk indentation; the static response of the nanoindentation is determined almost exclusively by the elastic properties of the nonfibrillar matrix and the volume fraction of fibers, while the transient response is dominated by the fluid permeability of the tissue. The FRPE model can accurately describe the time-dependent mechanical behavior of costal cartilage in nanoindentation, with good agreement between experimental and numerical curve fits (R(2)=0.98+/-0.01) at multiple indentation depths and indentation rates.

  6. Porcine models of muscular dystrophy.

    PubMed

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

    2015-01-01

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

  7. A study of the anatomy and repair strengths of porcine flexor and extensor tendons: are they appropriate experimental models?

    PubMed

    Mao, W F; Wu, Y F; Zhou, Y L; Tang, J B

    2011-10-01

    Although both porcine flexor and extensor tendons have been used in tendon repair research, no studies have specifically studied the anatomical differences and repair strengths in both types of tendons. We used 12 pig trotters to observe the anatomy of these tendons and compared the 2 mm gap and ultimate strengths of flexor and extensor tendons. There were four annular (A1, A2, A3, and A4) pulleys and one oblique pulley, which form a fibro-osseous tunnel for the flexor tendons, but the anatomy of the porcine extensor tendons was markedly different from the human flexor or extensor tendons. The diameter of flexor tendons was significantly greater than that of the extensors. The 2 mm gap and ultimate strengths of the flexor tendon with either two-strand or four-strand repairs were significantly greater than those of the extensor tendon. We conclude that the porcine flexor tendon systems are similar to those in the human, but the extensor tendons are not similar to either the flexor or extensor tendons in humans. Flexor and extensor tendons have different repair strengths which should be taken into account when interpreting findings from investigations using these tendons.

  8. Histological analysis of cobalt-chromium stents with and without Camouflage® polymer coating: experimental porcine carotid artery model.

    PubMed

    Grudtner, Marco Aurélio; de Lara Elesbão, Joao Luiz; Gutierrez, Paulo Sérgio; Meyer, Fabíola Schons; Pereira, Adamastor Humberto

    2011-04-01

    This study evaluated the arterial response to cobalt-chromium stents with and without polymer coating (Camouflage®, Hemoteq AG, Wuerselen, Germany) implanted in pigs. Cobalt-chromium balloon-expandable stents (4 × 16 mm) were implanted in the common carotid arteries of nine pigs. Histological analysis of endothelialization, inflammation and injury was performed one month later. All stents were successfully deployed, and all but one animal survived the 30 study days. All arteries were patent. Endothelialization was nearly complete in most sections of all carotid stents in both groups. There were mild inflammatory infiltrate and mild-to-moderate injury, which were associated with the stent shafts and not significantly different between groups. Our findings suggest that, in porcine carotid arteries, the histological response to balloon-expandable cobalt-chromium stents coated with polymer (Camouflage®, Hemoteq AG) is similar to the response to non-coated cobalt-chromium stents.

  9. Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model

    PubMed Central

    Matsumoto, Kazuyuki; Kato, Hironari; Tsutsumi, Koichiro; Fushimi, Soichiro; Iwamuro, Masaya; Oda, Shinsuke; Mizukawa, Sho; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Yamamoto, Naoki; Horiguchi, Shigeru; Okada, Hiroyuki

    2016-01-01

    Background Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. Methods Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. Results Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. Conclusions Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes. PMID:27594908

  10. Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model

    PubMed Central

    Matsumoto, Kazuyuki; Kato, Hironari; Tsutsumi, Koichiro; Fushimi, Soichiro; Iwamuro, Masaya; Oda, Shinsuke; Mizukawa, Sho; Akimoto, Yutaka; Uchida, Daisuke; Tomoda, Takeshi; Yamamoto, Naoki; Horiguchi, Shigeru; Okada, Hiroyuki

    2016-01-01

    Background Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. Methods Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. Results Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. Conclusions Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.

  11. Experimental transplacental transmission of porcine cytomegalovirus.

    PubMed

    Edington, N; Watt, R G; Plowright, W

    1977-04-01

    Six serologically negative sows were infected by intranasal instillation of porcine cytomegalovirus (PCMV) between 31 and 85 days of pregnacy. Four sows showed an afebrile anorexia and lethargy 14-25 days after infection and all 6 developed significant increases in indirect immunofluorescent (IIF) antibody titres within 35 days. Virus was recovered from nasal and/or cervical swabs from 2 sows during life and from lung macrophage cultures after death. At term the sows were killed and their fetuses harvested by caesarean section. The number of mummified and stillborn fetuses increased from 4/63 in 6 previous litters to 18/60 in the 6 present litters. Nine of 43 fetuses born alive were reared in isolators for up to 6 weeks but the majority were killed for examination on the day of birth. Virus was isolated from 16 piglets from 4 of the 6 litters examined; it was isolated most frequently from lungs and liver but also from spleen, kidney, brain and nasal mucosa. Unsuckled day-old pigs had insignificant IIF titres, irrespective of whether they were excreting virus or not. The 5 congenital excretors which were reared all died within 7 days but no death occurred among their 4 litter-mates. Post-natal infection of 2 of these piglets reared in contact with congenitally infected pigs was suggested by the recovery of virus from nasal swabs 17 and 27 days after birth and the subsequent rise in IIF titre to 1/256 by day 42.

  12. An experimental model to evaluate the role of transport vehicles as a source of transmission of porcine reproductive and respiratory syndrome virus to susceptible pigs.

    PubMed

    Dee, Scott A; Deen, John; Otake, Satoshi; Pijoan, Carlos

    2004-04-01

    The objectives of this study were to determine the concentration of porcine reproductive and respiratory syndrome virus (PRRSV) in a scale-model trailer that was required to infect susceptible pigs, evaluate the potential of PRRSV-contaminated transport vehicles to infect naïve pigs and assess 4 sanitation programs for the prevention of virus spread. To maximize study power, scale models (1:150) of weaned-pig trailers were constructed that provided an animal density equal to that of an actual weaned-pig trailer capable of transporting 300 pigs. The 1st aim involved contaminating the interior of the model trailers with various concentrations (10(1) to 10(4) TCID50/mL) of PRRSV MN 30-100, then housing sentinel pigs in the trailers for 2 h. Pigs exposed to trailers contaminated with > or = 10(3) TCID50/mL became infected. The 2nd aim involved housing experimentally infected seeder pigs in trailers for 2 h, then directly introducing sentinel pigs for 2 h. Infection of sentinels was demonstrated in 3 of 4 replicates. The 3rd aim involved applying 1 of 4 sanitation procedures (treatments) to contaminated trailers. Treatment 1 consisted of manual scraping of the interior to remove soiled bedding (wood chips). Treatment 2 consisted of bedding removal, washing (80 degrees C, 20,500 kPa), and disinfecting (with 1:256 phenol; 10-min contact time). Treatment 3 consisted of treatment 2, followed by freezing and thawing. Treatment 4 consisted of bedding removal, washing, disinfecting, and drying. Ten replicates were conducted per treatment. Pretreatment swabs from all trailers tested positive by polymerase chain reaction (PCR). Post-treatment swabs were PCR-positive for all trailers except those that were washed, disinfected, and dried. Infection of sentinel pigs by PRRSV was also detected by PCR after all treatments except washing, disinfecting, and drying. Under the conditions of this study, drying appeared to be an important component of a sanitation program for ensuring

  13. Tissue Sampling Guides for Porcine Biomedical Models.

    PubMed

    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.

  14. Porcine models of muscular dystrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Porcine Models of Muscular Dystrophy1

    PubMed Central

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

    2015-01-01

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease. PMID:25991703

  16. Cholinesterase in porcine saliva: Analytical characterization and behavior after experimental stress.

    PubMed

    Tecles, Fernando; Escribano, Damián; Martínez-Miró, Silvia; Hernández, Fuensanta; Contreras, María Dolores; Cerón, José Joaquín

    2016-06-01

    The purpose of this study was to measure and characterize the enzyme cholinesterase (ChE) in porcine saliva, as well as to evaluate its behavior in experimental stressful conditions. The results of ChE characterization by using different substrates and the selective inhibitors ethopropazine and physostigmine showed that the main enzyme existing in porcine saliva was butyrylcholinesterase (BChE). An automated assay using butyrylthiocholine iodide as substrate was validated providing adequate reproducibility, linearity results and limit of detection. Salivary ChE was measured using the validated assay in two models of acute stress: twenty pigs stressed for 2min with a nasal snare and other twenty pigs subjected to a short-term road transport. Salivary ChE significantly increased after restraint and transport stress in pigs, as well as the ChE to total protein ratio. In conclusion, BChE is the predominant isoenzyme in porcine saliva, it can be measured by the fast, simple and automated method described in this paper and it increases in the models of stress used in this study. PMID:27234531

  17. A porcine model for acute ischaemic right ventricular dysfunction

    PubMed Central

    Haraldsen, Pernille; Lindstedt, Sandra; Metzsch, Carsten; Algotsson, Lars; Ingemansson, Richard

    2014-01-01

    OBJECTIVES To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes. METHODS An open-chest porcine model with ischaemic dysfunction of the right ventricle induced by ligation of the three main branches supporting the right ventricular free wall. Invasive monitoring of mean arterial blood pressure (MAP), central venous pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP); ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic parameters such as stroke volume (SV), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) using standard formulae. RESULTS The ischaemic challenge to the right ventricle resulted in a significant (≥30%) reduction in RVSW associated with an increase (6–25%) in CVP and reduction (8–18%) in pulmonary artery pressure (PAP) despite unchanged PVR, all reflecting the failing right ventricle. There was also a significant drop in CO (14–22%) despite unchanged LAP indicating lessened transpulmonary delivery of left ventricular preload due to the failing right ventricle causing the haemodynamic compromise rather than left ventricular failure. Supraventricular and ventricular arrhythmias occurred in three and two out of seven pigs, respectively—all of which except one were successfully resuscitated with cardioversion and/or defibrillation. CONCLUSIONS This novel open-chest porcine model of induced ischaemia of the right ventricular free wall resulted in significant haemodynamic compromise confirmed using standard haemodynamic measurements making it useful for further research on acute, ischaemic isolated right ventricular failure. PMID:24092465

  18. A Genetic Porcine Model of Cancer

    PubMed Central

    Schook, Lawrence B.; Collares, Tiago V.; Hu, Wenping; Liang, Ying; Rodrigues, Fernanda M.; Rund, Laurie A.; Schachtschneider, Kyle M.; Seixas, Fabiana K.; Singh, Kuldeep; Wells, Kevin D.; Walters, Eric M.; Prather, Randall S.; Counter, Christopher M.

    2015-01-01

    The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic “oncopig” line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer. PMID:26132737

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

    PubMed

    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

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

    PubMed

    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.

  1. Porous Gelatin Particles for Uterine Artery Embolization: An Experimental Study of Intra-Arterial Distribution, Uterine Necrosis, and Inflammation in a Porcine Model

    SciTech Connect

    Sone, Miyuki; Osuga, Keigo; Shimazu, Kohki; Higashihara, Hiroki; Nakazawa, Tetsuro; Kato, Kenichi; Tomabechi, Makiko; Ehara, Shigeru; Nakamura, Hironobu; Morii, Eiichi; Aozasa, Katsuyuki

    2010-10-15

    PurposeWe evaluated the location of porous gelatin particles (GP; Gelpart; Nippon Kayaku/Astellas, Tokyo, Japan) within the arterial vasculature and their acute effects on uterine necrosis and inflammation after uterine artery embolization (UAE) in swine.Materials and MethodsAdult nonpregnant pigs (n = 6) were allocated to either 1- (n = 3) or 2-mm GP (n = 3). Superselective and bilateral embolization of the uterine arteries was performed. All animals were killed 1 week after UAE. Macroscopic and microscopic findings, including the level of arterial occlusion and their effect on uterine necrosis and inflammation, were analyzed.ResultsAll UAE procedures were completed without severe complications. The macroscopic necrosis was seen in two animals in the 2-mm group with an extent of <50%. The location of the occluded arteries did not differ significantly between groups. The median diameters of the occluded arteries were 449 {mu}m (95% confidence interval [CI] 417-538 {mu}m) in the 1-mm GP group and 484 {mu}m (95% CI 370-560 {mu}m) in the 2-mm GP group. As for microscopic necrosis, no statistically significant difference was observed. The qualitative inflammatory reaction was significantly greater in the 2-mm GP group than in the 1-mm group (p < 0.001).ConclusionsBoth 1- and 2-mm GP occluded the arteries relevant to the target diameter for UAE in porcine uterus, presumably due to the plastic deformity. Both sizes of GP were associated with limited areas of necrosis; however, evaluation of inflammatory reaction was preliminary. Further study with adequate evaluation of inflammatory reactions is suggested.

  2. Expression of human CD46 has no effect on porcine circovirus type 2 infection and shedding in the experimental pig model.

    PubMed

    Hemann, Michelle; Shen, Hui-Gang; Beach, Nathan M; Meng, Xiang-Jin; Halbur, Patrick G; Opriessnig, Tanja

    2012-09-01

    Xenotransplantation of tissues from transgenic pigs with desired genetic modifications such as CD46 expression help minimize xenograft rejections. However, CD46 is a known receptor for some viruses. In this study, pigs transgenic for human CD46 (CD46-TG) and appropriate non-transgenic (non-TG) control pigs were utilized to determine possible differences in the level of replication and shedding of porcine circovirus type 2 (PCV2). Non-TG and CD46-TG were blocked by transgenic status and randomly divided into three groups: Non-TG negative controls (n = 3), non-TG-PCV2 (n = 10; PCV2a = 5, PCV2b = 5), and CD46-TG-PCV2 (n = 6; PCV2a = 3, PCV2b = 3). Blood, oral, nasal and fecal swabs were collected at regular intervals from the day of arrival until 70 days post inoculation (DPI). All samples were tested by quantitative real-time PCR for the presence of PCV2 DNA and serum was tested for presence of PCV2 antibodies by ELISA. Overall, the main effects "transgenic status" and "PCV2 subtype" had no influence on degree of PCV2 viremia and shedding or the anti-PCV2 humoral immune response in CD46-TG-PCV2 pigs compared to non-TG-PCV2 pigs. Differences in PCV2 concentrations between non-TG-PCV2 and CD46-TG-PCV2 pigs were minimal and limited to DPI 35 in sera, DPI 7 in fecal swabs and DPI 5 in nasal swabs when CD46-TG-PCV2 pigs had significantly higher concentrations of PCV2 DNA. At DPI 1, CD46-TG-PCV2 pigs had significantly lower concentrations of PCV2 DNA in oral swabs. Under the study conditions, the presence of human CD46 in transgenic pigs had no effect on PCV2 infection in otherwise healthy pigs capable of a normal immune response. PMID:22388862

  3. In vivo porcine training model for cranial neurosurgery.

    PubMed

    Regelsberger, Jan; Eicker, Sven; Siasios, Ioannis; Hänggi, Daniel; Kirsch, Matthias; Horn, Peter; Winkler, Peter; Signoretti, Stefano; Fountas, Kostas; Dufour, Henry; Barcia, Juan A; Sakowitz, Oliver; Westermaier, Thomas; Sabel, Michael; Heese, Oliver

    2015-01-01

    Supplemental education is desirable for neurosurgical training, and the use of human cadaver specimen and virtual reality models is routine. An in vivo porcine training model for cranial neurosurgery was introduced in 2005, and our recent experience with this unique model is outlined here. For the first time, porcine anatomy is illustrated with particular respect to neurosurgical procedures. The pros and cons of this model are described. The aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the brain and neurosurgical techniques in a mentored environment free from time constraints could be trained. Learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications. Participants were asked to evaluate the quality and utility of the programme via standardized questionnaires by a grading scale from A (best) to E (worst). In total, 154 residents have been trained on the porcine model to date. None of the participants regarded his own residency programme as structured. The bleeding and complication management (97%), the realistic laboratory set-up (89%) and the working environment (94%) were favoured by the vast majority of trainees and confirmed our previous findings. After finishing the course, the participants graded that their skills in bone drilling, dissecting the brain and preserving cerebral vessels under microscopic magnification had improved to level A and B. In vivo hands-on courses, fully equipped with microsurgical instruments, offer an outstanding training opportunity in which bleeding management on a pulsating, vital brain represents a unique training approach. Our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a complementary approach in surgical training.

  4. Development of a Consistent and Reproducible Porcine Scald Burn Model

    PubMed Central

    Kempf, Margit; Kimble, Roy; Cuttle, Leila

    2016-01-01

    There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

  5. Development of a Consistent and Reproducible Porcine Scald Burn Model.

    PubMed

    Andrews, Christine J; Kempf, Margit; Kimble, Roy; Cuttle, Leila

    2016-01-01

    There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

  6. Attempted Experimental Reproduction of Porcine Periweaning-Failure-to-Thrive Syndrome Using Tissue Homogenates

    PubMed Central

    Huang, Yanyun; Harding, John C. S.

    2014-01-01

    Porcine periweaning failure-to-thrive syndrome (PFTS) is characterized by anorexia and progressive debilitation of newly weaned pigs, of which some also demonstrate repetitive oral behaviour. Although no relevant porcine pathogens have been shown to be causally associated, inoculation of susceptible pigs using tissue homogenates is needed to rule out infectious etiologies. Eight snatched-farrowed porcine-colostrum-deprived (SF-pCD) pigs were inoculated with tissue homogenates made from PFTS-affected pigs orally, or combined orally, intraperitoneally (IP) and intramuscularly (IM) at day (D) 14 of age (INOC). On D21, IP and IM inoculation were repeated. Four sham-inoculated pigs served as control (CTRL). Three INOC pigs developed mixed bacterial septicemia between the first and second inoculation. All other pigs survived until termination on D49. Average daily gain (ADG) and the frequencies of diarrhea did not differ between INOC and CTRL pigs D14 and D29. Additionally, the progressive debilitation characteristic of PFTS was not observed in any pig, and repetitive oral behaviour was observed in both groups. In conclusion, PFTS was not experimentally reproduced by the current experimental approach providing evidence that PFTS may not have an infectious etiology. PMID:24594806

  7. Acoustic hemostasis of porcine superficial femoral artery: Simulation and in-vivo experimental studies

    NASA Astrophysics Data System (ADS)

    Zeng, Xiaozheng; Mitchell, Stuart; Miller, Matthew; Barnes, Stephen; Hopple, Jerry; Kook, John; Moreau-Gobard, Romain; Hsu, Stephen; Ahiekpor-Dravi, Alexis; Crum, Lawrence A.; Eaton, John; Wong, Keith; Sekins, K. Michael

    2012-10-01

    In-vivo focused ultrasound studies were computationally simulated and conducted experimentally with the aim of occluding porcine superficial femoral arteries (SFA) via thermal coagulation. A multi-array HIFU applicator was used which electronically scanned multiple beam foci around the target point. The spatio-temporally averaged acoustic and temperature fields were simulated in a fluid dynamics and acousto-thermal finite element model with representative tissue fields, including muscle, vessel and blood. Simulations showed that with an acoustic power of 200W and a dose time of 60s, perivascular tissue reached 91°C; and yet blood reached a maximum 59°C, below the coagulation objective for this dose regime (75°C). Per simulations, acoustic-streaming induced velocity in blood reached 6.1cm/s. In in-vivo experiments, several arteries were treated. As simulated, thermal lesions were observed in muscle surrounding SFA in all cases. In dosing limited to 30 to 60 seconds, it required 257W to provide occlusion (one complete and one partial occlusion). Angiography and histology showed evidence of thrombogenesis and collagen shrinkage-based vessel constriction at these doses.

  8. Porcine models of cutaneous wound healing.

    PubMed

    Seaton, Max; Hocking, Anne; Gibran, Nicole S

    2015-01-01

    Cutaneous wound healing in the pig is frequently used as a model for human cutaneous wound healing. In this review, we examine the appropriateness of this model for studying normal and pathological wound healing, and describe models for chronic nonhealing wounds, diabetic wounds, burns, and hypertrophic scars. In addition, we focus on studies that have used pigs to evaluate wound-healing therapies, and discuss genetic engineering technology in the pig that may advance our knowledge of wound healing. We conclude that, although not perfect, the pig offers a versatile model that can be adjusted to mimic a wide range of clinical scenarios.

  9. Comparison of modified Kessler tendon suture at different levels in the human flexor digitorum profundus tendon and porcine flexors and porcine extensors: an experimental biomechanical study.

    PubMed

    Havulinna, J; Leppänen, O V; Järvinen, T L N; Göransson, H

    2011-10-01

    This study compared the biomechanical behaviour of repairs in the human flexor digitorum profundus tendon in zones I, II and III with repairs of different segments of the porcine flexor tendon of the second digit and the extensor digiti quarti proprius tendon, in order to assess the validity of porcine tendons as models for human flexor tendon repairs. These porcine tendons were selected after comparing their size with the human flexor digitorum profundus tendon. The tendon repairs were done in three segments of each porcine tendon and repairs in the human tendons were done in zones I,II and III. Ten tendons in each group yielded a total of 90 specimens. A modified Kessler repair was done with 3-0 coated braided polyester suture and subjected to uniaxial tensile testing. In human flexor tendons, the ultimate force was higher in zones I and II than in zone III. The porcine flexor digitorum profundus tendon from the second digit and the proximal segment of the extensor digiti quarti proprius tendon behaved similarly to the human flexor tendon in zone III and can be considered as surrogates for the human flexor tendon. PMID:21816887

  10. Material Properties and Constitutive Modeling of Infant Porcine Cerebellum Tissue in Tension at High Strain Rate

    PubMed Central

    Li, Kui; Zhao, Hui; Liu, Wenjun; Yin, Zhiyong

    2015-01-01

    Background The mechanical characterization of infant porcine cerebellum tissue in tension at high strain rate is crucial for modeling traumatic cerebellum injury, which is in turn helpful for understanding the biomechanics of such injuries suffered in traffic accidents. Material and Method In this study, the infant porcine cerebellum tissue was given three loading velocities, ie, 2s-1, 20s-1 and 100s-1 with up to 30% strain to investigate the tensile properties. At least six tensile tests for each strain rate were validly performed. Fung, Gent, Ogden and exponential models were applied to fit the constitutive equations, so as to obtain material parameters from the experimental data. Results The Lagrange stress of infant porcine cerebellum tissue in tension appeared to be no more than 3000Pa at each loading velocity. More specifically, the Lagrange stress at 30% strain was (393.7±84.4)Pa, (928.3±56.3)Pa and (2582.4±282.2)Pa at strain rates of 2s-1, 20s-1 and 100s-1, respectively. Fung (0.833≤R2≤0.924), Gent (0.797≤R2≤0.875), Ogden (0.859≤R2≤0.944) and exponential (0.930≤R2≤0.972) models provided excellent fitting to experimental data up to 30% strain. Conclusions The infant cerebellum tissue shows a stiffer response with increase of the loading speed, indicating a strong strain-rate sensitivity. This study will enrich the knowledge on the material properties of infant brain tissue, which may augment the biofidelity of finite element model of human pediatric cerebellum. PMID:25830545

  11. Robot-Assisted Pterygium Surgery: Feasibility Study in a Nonliving Porcine Model

    PubMed Central

    Bourcier, Tristan; Nardin, Mathieu; Sauer, Arnaud; Gaucher, David; Speeg, Claude; Mutter, Didier; Marescaux, Jacques; Liverneaux, Philippe

    2015-01-01

    Purpose This study aims to investigate the feasibility of pterygium surgery using the DaVinci Si HD robotic surgical system, and to describe a porcine model for pterygium surgery and evaluate its usefulness. Methods The pterygium models were constructed using enucleated pig eyes and cold cuts. Robotically-assisted pterygium surgeries in nonliving biological pterygium models were performed using the DaVinci Si HD robotic surgical system. Twelve models were prepared, and 12 pterygium excision and conjunctival autografts were performed. Results The DaVinci system provided the necessary dexterity to perform delicate ocular surface surgery and robotic tools were safe for the tissues. The mean duration of the surgical procedures was 36 minutes. There were no intraoperative complications and no unexpected events. Conclusions Robotic-assisted pterygium surgery is technically feasible for porcine eyes using the DaVinci Si HD robotic surgical system. The pterygium model that we describe could be of interest for surgical training. Translational Relevance Little research has been done in robotic microsurgery. Animal experimentation will allow the advantages of robotic-assisted microsurgery to be identified, while underlining the improvements and innovations necessary for clinical use. PMID:25722953

  12. Myocardial Scar Imaging by Standard Single-Energy and Dual-Energy Late Enhancement Computed Tomography: Comparison to Pathology and Electroanatomical Map in an Experimental Chronic Infarct Porcine Model

    PubMed Central

    Truong, Quynh A.; Thai, Wai-ee; Wai, Bryan; Cordaro, Kevin; Cheng, Teresa; Beaudoin, Jonathan; Xiong, Guanglei; Cheung, Jim W.; Altman, Robert; Min, James K.; Singh, Jagmeet P.; Barrett, Conor D.; Danik, Stephan

    2015-01-01

    Background Myocardial scar is a substrate for ventricular tachycardia and sudden cardiac death. Late enhancement computed tomography (CT) imaging can detect scar, but it remains unclear whether newer late enhancement dual-energy (LE-DECT) acquisition has benefit over standard single-energy late enhancement (LE-CT). Objective We aim to compare late enhancement CT using newer LE-DECT acquisition and single-energy LE-CT acquisitions to pathology and electroanatomical map (EAM) in an experimental chronic myocardial infarction (MI) porcine study. Methods In 8 chronic MI pigs (59±5 kg), we performed dual-source CT, EAM, and pathology. For CT imaging, we performed 3 acquisitions at 10 minutes post-contrast: LE-CT 80 kV, LE-CT 100 kV, and LE-DECT with two post-processing software settings. Results Of the sequences, LE-CT 100 kV provided the best contrast-to-noise ratio (all p≤0.03) and correlation to pathology for scar (ρ=0.88). While LE-DECT overestimated scar (both p=0.02), LE-CT images did not (both p=0.08). On a segment basis (n=136), all CT sequences had high specificity (87–93%) and modest sensitivity (50–67%), with LE-CT 100 kV having the highest specificity of 93% for scar detection compared to pathology and agreement with EAM (κ 0.69). Conclusions Standard single-energy LE-CT, particularly 100kV, matched better to pathology and EAM than dual-energy LE-DECT for scar detection. Larger human trials as well as more technical-based studies that optimize varying different energies with newer hardware and software are warranted. PMID:25977115

  13. Biphasic Presence of Fibrocytes in a Porcine Hypertrophic Scar Model

    PubMed Central

    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.

    2014-01-01

    Objective 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. Methods Wounds known to form scar were created on red duroc swine (3“ × 3”) with a dermatome to a total depth of either 0.06“ or 0.09”. These wounds were allowed to heal completely and were biopsied 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. Results Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06“ 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” 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 diffuse in all samples. Cultured cells stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. Conclusions 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 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

  14. Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models.

    PubMed

    Schook, Lawrence B; Rund, Laurie; Begnini, Karine R; Remião, Mariana H; Seixas, Fabiana K; Collares, Tiago

    2016-01-01

    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. PMID:26973698

  15. Evaluation of Wedged Arterial Injection as a New Technique for Delivery of Experimental Therapeutic Sustances into the Porcine Pancreas

    PubMed Central

    Latorre, Rafael; Hernández, Wendy; Sun, Fei; Sánchez-Margallo, Francisco; Gil, Francisco; López-Albors, Octavio; Vázquez, Jose M.; Usón, Jesús

    2011-01-01

    Objectives. To prospectively evaluate the technical feasibility and efficacy of wedged arterial injection (WAI) as a potential route for experimental selective therapy to the pancreas of healthy pigs. Materials and Methods. Selective angiographies were completed in ten pigs under general anaesthesia. By superselective angiography, the catheter was inserted and wedged into the major pancreatic artery, blocking the blood flow. In order to evaluate the efficacy of the WAI method, a DNA-specific fluorescent dye (Hoechst 33258) was used. Results. Histological study revealed a uniform distribution of the fluorescent dye within the nuclei of the endocrine and exocrine pancreatic cells. Pancreatic and liver enzymes as well as histopathology of the pancreas were normal. Conclusion. WAI is a highly effective minimally invasive methodology to target the porcine pancreas. The findings suggest that WAI may contribute to developing preclinical assays of pancreas gene or cell-transfer therapies in swine model. PMID:22007190

  16. Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol.

    PubMed

    Kaths, J Moritz; Echeverri, Juan; Goldaracena, Nicolas; Louis, Kristine S; Yip, Paul; John, Rohan; Mucsi, Istvan; Ghanekar, Anand; Bagli, Darius; Selzner, Markus; Robinson, Lisa A

    2016-01-01

    Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication. PMID

  17. Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

    PubMed Central

    Kaths, J. Moritz; Echeverri, Juan; Goldaracena, Nicolas; Louis, Kristine S.; Yip, Paul; John, Rohan; Mucsi, Istvan; Ghanekar, Anand; Bagli, Darius; Selzner, Markus; Robinson, Lisa A.

    2016-01-01

    Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication. PMID

  18. A comprehensive computational model of sound transmission through the porcine lung.

    PubMed

    Dai, Zoujun; Peng, Ying; Henry, Brian M; Mansy, Hansen A; Sandler, Richard H; Royston, Thomas J

    2014-09-01

    A comprehensive computational simulation model of sound transmission through the porcine lung is introduced and experimentally evaluated. This "subject-specific" model utilizes parenchymal and major airway geometry derived from x-ray CT images. The lung parenchyma is modeled as a poroviscoelastic material using Biot theory. A finite element (FE) mesh of the lung that includes airway detail is created and used in comsol FE software to simulate the vibroacoustic response of the lung to sound input at the trachea. The FE simulation model is validated by comparing simulation results to experimental measurements using scanning laser Doppler vibrometry on the surface of an excised, preserved lung. The FE model can also be used to calculate and visualize vibroacoustic pressure and motion inside the lung and its airways caused by the acoustic input. The effect of diffuse lung fibrosis and of a local tumor on the lung acoustic response is simulated and visualized using the FE model. In the future, this type of visualization can be compared and matched with experimentally obtained elastographic images to better quantify regional lung material properties to noninvasively diagnose and stage disease and response to treatment. PMID:25190415

  19. A comprehensive computational model of sound transmission through the porcine lung

    PubMed Central

    Dai, Zoujun; Peng, Ying; Henry, Brian M.; Mansy, Hansen A.; Sandler, Richard H.; Royston, Thomas J.

    2014-01-01

    A comprehensive computational simulation model of sound transmission through the porcine lung is introduced and experimentally evaluated. This “subject-specific” model utilizes parenchymal and major airway geometry derived from x-ray CT images. The lung parenchyma is modeled as a poroviscoelastic material using Biot theory. A finite element (FE) mesh of the lung that includes airway detail is created and used in comsol FE software to simulate the vibroacoustic response of the lung to sound input at the trachea. The FE simulation model is validated by comparing simulation results to experimental measurements using scanning laser Doppler vibrometry on the surface of an excised, preserved lung. The FE model can also be used to calculate and visualize vibroacoustic pressure and motion inside the lung and its airways caused by the acoustic input. The effect of diffuse lung fibrosis and of a local tumor on the lung acoustic response is simulated and visualized using the FE model. In the future, this type of visualization can be compared and matched with experimentally obtained elastographic images to better quantify regional lung material properties to noninvasively diagnose and stage disease and response to treatment. PMID:25190415

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

    PubMed

    Barkalina, Natalia; Jones, Celine; Coward, Kevin

    2016-01-01

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

  1. Identification of a Divergent Lineage Porcine Pestivirus in Nursing Piglets with Congenital Tremors and Reproduction of Disease following Experimental Inoculation

    PubMed Central

    Arruda, Bailey L.; Arruda, Paulo H.; Magstadt, Drew R.; Schwartz, Kent J.; Dohlman, Tyler; Schleining, Jennifer A.; Patterson, Abby R.; Visek, Callie A.; Victoria, Joseph G.

    2016-01-01

    Congenital tremors is a sporadic disease of neonatal pigs characterized by action-related repetitive myoclonus. A majority of outbreaks of congenital tremors have been attributed to an unidentified virus. The objectives of this project were to 1) detect potential pathogen(s) in samples from piglets with congenital tremors and 2) develop an infection model to reproduce disease. Using next-generation sequencing, a divergent lineage pestivirus was detected in piglets with congenital tremors. The virus was originally most closely related to a bat pestivirus but is now more closely related to a recently published novel porcine pestivirus provisionally named atypical porcine pestivirus. A quantitative real-time PCR detected the virus in samples from neonatal piglets with congenital tremors from two separate farms, but not in samples from unaffected piglets from the same farm. To fulfill the second objective, pregnant sows were inoculated with either serum containing the pestivirus or PBS (control) by intravenous and intranasal routes simultaneously with direct inoculation of fetal amniotic vesicles by ultrasound-guided surgical technique. Inoculations were performed at either 45 or 62 days of gestation. All sows inoculated with the novel pestivirus farrowed piglets affected with congenital tremors while PBS-inoculated control piglets were unaffected. Tremor severity for each piglet was scored from videos taken 0, 1 and 2 days post-farrowing. Tremor severity remained relatively constant from 0 to 2 days post-farrowing for a majority of piglets. The prevalence of congenital tremors in pestivirus-inoculated litters ranged from 57% (4 out of 7 affected piglets) to 100% (10 out of 10 affected piglets). The virus was consistently detected by PCR in tissues from piglets with congenital tremors but was not detected in control piglets. Samples positive by PCR in greater than 90% of piglets sampled included brainstem (37 out of 41), mesenteric lymph node (37 out of 41

  2. Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus.

    PubMed

    Jung, Bock-Gie; Lee, Jin-A; Lee, Bong-Joo

    2013-01-01

    Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.

  3. Thermal epiphysiodesis performed with radio frequency in a porcine model

    PubMed Central

    Shiguetomi-Medina, Juan M; Rahbek, Ole; Abood, Ahmed Abdul-Hussein; Stødkilde-Jørgensen, Hans; Møller-Madsen, Bjarne

    2014-01-01

    Background and purpose Current techniques for epiphysiodesis involve opening of cortical windows; use of staples, screws, and tension devices; and fusion with curettes or drills. Complications may have serious consequences. There is a need for a more reliable, precise, and less traumatic procedure that overcomes the known complications from existing techniques. We analyzed a new epiphysiodesis technique using radio-frequency ablation (RFA) in a porcine model. Methods Six 35-kg and two 25-kg immature pigs were used. 1 hind leg of each animal was randomly selected and the proximal tibia growth plate was ablated laterally and medially. The contralateral leg was used as a control. MR images were obtained immediately after the ablation and 12 weeks later for 6 animals, and 24 weeks later for the other 2 animals. CT was done for the 2 animals that were followed for 24 weeks for proof of bone bridges. Results Both tibias were equal in length initially. At the 12-week follow-up, there was an average leg length discrepancy of 3.9 mm (95% CI: 3.0–4.8), and at 24 weeks the difference was 8.4 mm and 7.5 mm. No damage to the adjacent tissue was found. Bone bridges and physeal closure were found after 24 weeks. The pigs showed no discomfort after the intervention. Interpretation We found RFA to be feasible for epiphysiodesis in a pig model. The method is minimally invasive and recovery may be quick compared to conventional methods. We recommend that the method should be tested in larger-scale safety studies before clinical application. PMID:25036720

  4. Computational biomechanics and experimental validation of vessel deformation based on 4D-CT imaging of the porcine aorta

    NASA Astrophysics Data System (ADS)

    Hazer, Dilana; Finol, Ender A.; Kostrzewa, Michael; Kopaigorenko, Maria; Richter, Götz-M.; Dillmann, Rüdiger

    2009-02-01

    Cardiovascular disease results from pathological biomechanical conditions and fatigue of the vessel wall. Image-based computational modeling provides a physical and realistic insight into the patient-specific biomechanics and enables accurate predictive simulations of development, growth and failure of cardiovascular disease. An experimental validation is necessary for the evaluation and the clinical implementation of such computational models. In the present study, we have implemented dynamic Computed-Tomography (4D-CT) imaging and catheter-based in vivo measured pressures to numerically simulate and experimentally evaluate the biomechanics of the porcine aorta. The computations are based on the Finite Element Method (FEM) and simulate the arterial wall response to the transient pressure-based boundary condition. They are evaluated by comparing the numerically predicted wall deformation and that calculated from the acquired 4D-CT data. The dynamic motion of the vessel is quantified by means of the hydraulic diameter, analyzing sequences at 5% increments over the cardiac cycle. Our results show that accurate biomechanical modeling is possible using FEM-based simulations. The RMS error of the computed hydraulic diameter at five cross-sections of the aorta was 0.188, 0.252, 0.280, 0.237 and 0.204 mm, which is equivalent to 1.7%, 2.3%, 2.7%, 2.3% and 2.0%, respectively, when expressed as a function of the time-averaged hydraulic diameter measured from the CT images. The present investigation is a first attempt to simulate and validate vessel deformation based on realistic morphological data and boundary conditions. An experimentally validated system would help in evaluating individual therapies and optimal treatment strategies in the field of minimally invasive endovascular surgery.

  5. A meta-analysis on experimental infections with porcine circovirus type 2 (PCV2).

    PubMed

    Tomás, Anna; Fernandes, Lana T; Valero, Oliver; Segalés, Joaquim

    2008-12-10

    A meta-analysis was performed with the aim to identify factors with a relevant influence on the expression of clinical postweaning multisystemic wasting syndrome (PMWS) under experimental conditions. Data from 44 studies were included in the analysis. Several variables were studied: number of pigs in the experiment, intake of colostrum, serological status against porcine circovirus type 2 (PCV2), strain of PCV2 used for inoculation, the route and dose of inoculation, and use of potential triggering factors (such as co-infections, vaccinations, or immunomodulator products). Multiple correspondence analysis and log-linear regression methods were used to establish the relationships between the studied variables and the number of PCV2 infected pigs that developed PMWS. Based on the results of the meta-analysis, the most successful animal experiment aimed to develop PMWS should include: (1) colostrum-deprived pigs, (2) age of inoculation below 3 weeks, (3) high doses of PCV2 inoculum, (4) PCV2 strain from genotype 1, and (5) co-infection with another swine pathogen as a triggering factor.

  6. Improved Cell Line IPEC-J2, Characterized as a Model for Porcine Jejunal Epithelium

    PubMed Central

    Zakrzewski, Silke S.; Richter, Jan F.; Krug, Susanne M.; Jebautzke, Britta; Lee, In-Fah M.; Rieger, Juliane; Sachtleben, Monika; Bondzio, Angelika; Schulzke, Jörg D.; Fromm, Michael; Günzel, Dorothee

    2013-01-01

    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. PMID:24260272

  7. Vaccination with a genotype 1 modified live vaccine against porcine reproductive and respiratory syndrome virus significantly reduces viremia, viral shedding and transmission of the virus in a quasi-natural experimental model.

    PubMed

    Pileri, Emanuela; Gibert, Elisa; Soldevila, Ferran; García-Saenz, Ariadna; Pujols, Joan; Diaz, Ivan; Darwich, Laila; Casal, Jordi; Martín, Marga; Mateu, Enric

    2015-01-30

    The present study assessed the efficacy of vaccination against genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV) in terms of reduction of the transmission. Ninety-eight 3-week-old piglets were divided in two groups: V (n=40) and NV (n=58) that were housed separately. V animals were vaccinated with a commercial genotype 1 PRRSV vaccine while NV were kept as controls. On day 35 post-vaccination, 14 NV pigs were separated and inoculated intranasally with 2 ml of a heterologous genotype 1 PRRSV isolate ("seeder" pigs, SP). The other V and NV animals were distributed in groups of 5 pigs each. Two days later, one SP was introduced into each pen to expose V and NV to PRRSV. Sentinel pigs were allocated in adjacent pens. Follow-up was of 21 days. All NV (30/30) became viremic after contact with SP while only 53% of V pigs were detected so (21/40, p<0.05). Vaccination shortened viremia (12.2±4 versus 3.7±3.4 days in NV and V pigs, respectively, p<0.01). The 50% survival time for becoming infected (Kaplan-Meier) for V was 21 days (CI95%=14.1-27.9) compared to 7 days (CI95%=5.2-8.7) for NV animals (p<0.01). These differences were reflected in the R value as well: 2.78 (CI95%=2.13-3.43) for NV and 0.53 (CI95%=0.19-0.76) for V pigs (p<0.05). All sentinel pigs (10/10) in pens adjacent to NV+SP pens got infected compared to 1/4 sentinel pigs allocated contiguous to a V+SP pen. These data show that vaccination of piglets significantly decrease parameters related to PRRSV transmission. PMID:25439650

  8. Vaccination with a genotype 1 modified live vaccine against porcine reproductive and respiratory syndrome virus significantly reduces viremia, viral shedding and transmission of the virus in a quasi-natural experimental model.

    PubMed

    Pileri, Emanuela; Gibert, Elisa; Soldevila, Ferran; García-Saenz, Ariadna; Pujols, Joan; Diaz, Ivan; Darwich, Laila; Casal, Jordi; Martín, Marga; Mateu, Enric

    2015-01-30

    The present study assessed the efficacy of vaccination against genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV) in terms of reduction of the transmission. Ninety-eight 3-week-old piglets were divided in two groups: V (n=40) and NV (n=58) that were housed separately. V animals were vaccinated with a commercial genotype 1 PRRSV vaccine while NV were kept as controls. On day 35 post-vaccination, 14 NV pigs were separated and inoculated intranasally with 2 ml of a heterologous genotype 1 PRRSV isolate ("seeder" pigs, SP). The other V and NV animals were distributed in groups of 5 pigs each. Two days later, one SP was introduced into each pen to expose V and NV to PRRSV. Sentinel pigs were allocated in adjacent pens. Follow-up was of 21 days. All NV (30/30) became viremic after contact with SP while only 53% of V pigs were detected so (21/40, p<0.05). Vaccination shortened viremia (12.2±4 versus 3.7±3.4 days in NV and V pigs, respectively, p<0.01). The 50% survival time for becoming infected (Kaplan-Meier) for V was 21 days (CI95%=14.1-27.9) compared to 7 days (CI95%=5.2-8.7) for NV animals (p<0.01). These differences were reflected in the R value as well: 2.78 (CI95%=2.13-3.43) for NV and 0.53 (CI95%=0.19-0.76) for V pigs (p<0.05). All sentinel pigs (10/10) in pens adjacent to NV+SP pens got infected compared to 1/4 sentinel pigs allocated contiguous to a V+SP pen. These data show that vaccination of piglets significantly decrease parameters related to PRRSV transmission.

  9. Evaluation of hands-on seminar for reduced port surgery using fresh porcine cadaver model

    PubMed Central

    Poudel, Saseem; Kurashima, Yo; Shichinohe, Toshiaki; Kitashiro, Shuji; Kanehira, Eiji; Hirano, Satoshi

    2016-01-01

    BACKGROUND: The use of various biological and non-biological simulators is playing an important role in training modern surgeons with laparoscopic skills. However, there have been few reports of the use of a fresh porcine cadaver model for training in laparoscopic surgical skills. The purpose of this study was to report on a surgical training seminar on reduced port surgery using a fresh cadaver porcine model and to assess its feasibility and efficacy. MATERIALS AND METHODS: The hands-on seminar had 10 fresh porcine cadaver models and two dry boxes. Each table was provided with a unique access port and devices used in reduced port surgery. Each group of 2 surgeons spent 30 min at each station, performing different tasks assisted by the instructor. The questionnaire survey was done immediately after the seminar and 8 months after the seminar. RESULTS: All the tasks were completed as planned. Both instructors and participants were highly satisfied with the seminar. There was a concern about the time allocated for the seminar. In the post-seminar survey, the participants felt that the number of reduced port surgeries performed by them had increased. CONCLUSION: The fresh cadaver porcine model requires no special animal facility and can be used for training in laparoscopic procedures. PMID:27279391

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

    PubMed

    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.

  11. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to characterize the infection dynamics and pathogenicity of two heterologous type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a conventional pig model under the influence of concurrent porcine circovirus (PCV) subtype 2a or 2b infection. ...

  12. Minimally Invasive Swine Experimental Model for the In Vivo Study of Liver Metabolism of Drugs

    PubMed Central

    Piazza, O; Romano, R; Scarpati, G; Esposito, C; Cavaglià, E; Corona, M

    2012-01-01

    Purpose To develop a clinically relevant porcine model for the study of hepatic metabolism of drugs by means of hepatic vein catheterization. Materials and Methods: review of literature and elaboration of a hypothesis, design of an experimental method. Results: recent clinical studies were conducted by withdrawing cirrhotic patients’ blood from right hepatic vein during hepatic vein pressure gradient measurements. Basing on our personal clinical experience and evaluation of research needs, an experimental model is proposed. Conclusions: contemporary measurement of peripheral and hepatic concentration of drugs by peripheral vein and hepatic vein catheterization can be used to create a reliable and reproducible porcine model to study liver metabolism of drugs in vivo. PMID:23905064

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

    PubMed Central

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

    2016-01-01

    The persistence of back pain following acute back “sprains” is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a “hobble” device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted. PMID:26820883

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

    PubMed

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

    2016-01-01

    The persistence of back pain following acute back "sprains" is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a "hobble" device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted. PMID:26820883

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

    PubMed

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

    2016-01-01

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

  16. A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains

    PubMed Central

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

    2016-01-01

    Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID:26999052

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

    PubMed

    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.

  18. Porcine gonadogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five images submitted for teaching purposes related to porcine gonadogenesis (2), porcine fetal testicular development (2), and porcine fetal ovarian development. Key words include: Egg cell nests, Embryo, GATA4, Genital ridge, Gonad, Leydig cell, Mesonephros, MIS, Ovary, P450c17, Porcine, Sertoli ...

  19. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

    PubMed Central

    Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong; Li, Yongqin

    2015-01-01

    Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

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

    PubMed Central

    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

  1. Aortic Implantation of Mesenchymal Stem Cells after Aneurysm Injury in a Porcine Model

    PubMed Central

    Turnbull, Irene C.; Hadri, Lahouaria; Rapti, Kleopatra; Sadek, Mikel; Liang, Lifan; Shin, Hyun J.; Costa, Kevin D.; Marin, Michael L.; Hajjar, Roger J.; Faries, Peter L.

    2011-01-01

    Background Cell based therapies are being evaluated in the setting of degenerative pathophysiological conditions. The search for the ideal method of delivery and improvement in cell engraftment continue to pose a challenge. This study explores the feasibility of introducing mesenchymal stem cells (MSC) following aortic injury in a porcine model. Methods Bone marrow derived MSC were obtained from 8 pigs, characterized for the MSC markers CD13 and CD 29, labeled with green fluorescent protein (GFP), and collected for autologous injection in a porcine model of abdominal aortic aneurysm (AAA). The pigs were euthanized (1–7 days) after the procedure to assess the histological characteristics and presence of MSC in the aortic tissue. Negative controls included non-injured aorta. Tracking of the MSC was conducted by the identification of the GFP labeled cells using immunofluorescence. Results AAA sections stained with hematoxylin and eosin showed disorganization of the aortic tissue; collagen-muscle-elastin stain demonstrated fragmentation of elastin fibers. The presence of the implanted MSC in the aortic wall was evidenced by fluorescent microscopy showing GFP labeled cells. Engraftment of MSC up to 7 days after introduction was observed. Conclusion . Autologous implantation of bone marrow derived MSC following aortic injury in a porcine model may be successfully accomplished. The long term impact and therapeutic value of such cell-based therapy will require further investigation. PMID:21764076

  2. Shear mechanical properties of the porcine pancreas: experiment and analytical modelling.

    PubMed

    Nicolle, S; Noguer, L; Palierne, J-F

    2013-10-01

    We provide the first account of the shear mechanical properties of porcine pancreas using a rheometer both in linear oscillatory tests and in constant strain-rate tests reaching the non-linear sub-failure regime. Our results show that pancreas has a low and weakly frequency-dependent dynamic modulus and experiences a noticeable strain-hardening beyond 20% strain. In both linear and non-linear regime, the viscoelastic behaviour of porcine pancreas follows a four-parameter bi-power model that has been validated on kidney, liver and spleen. Among the four solid organs of the abdomen, pancreas proves to be the most compliant and the most viscous one. PMID:23820244

  3. Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

    SciTech Connect

    Veluraja, K.; Vennila, K.N.; Umamakeshvari, K.; Jasmine, A.; Velmurugan, D.

    2011-03-25

    Research highlights: {yields} Techniques to get oriented mucin fibre. {yields} X-ray fibre diffraction pattern for mucin. {yields} Molecular modeling of mucin based on X-ray fibre diffraction pattern. -- Abstract: The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 A. The high intense d-spacing signal at 4.22 A is attributed to the antiparallel {beta}-sheet structure identified in the fraction of the homology modeled mucin molecule (amino acid residues 800-980) using Nidogen-Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 A reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.

  4. Experimental Models of Cryptococcosis

    PubMed Central

    Sabiiti, Wilber; May, Robin C.; Pursall, E. Rhiannon

    2012-01-01

    Cryptococcosis is a life-threatening fungal disease that infects around one million people each year. Establishment and progression of disease involves a complex interplay between the fungus and a diverse range of host cell types. Over recent years, numerous cellular, tissue, and animal models have been exploited to probe this host-pathogen interaction. Here we review the range of experimental models that are available for cryptococcosis research and compare the relative advantages and limitations of the different systems. PMID:22007224

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

    PubMed

    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

  6. Ischemic etiopathogenesis as the possible origin of post-double baloon enteroscopy pancreatitis. A porcine model study.

    PubMed

    Soria, Federico; Pérez-Cuadrado, Enrique; López-Albors, Octavio; Morcillo, Esther; Sarriá, Ricardo; Candanosa, Eugenia; Esteban, Pilar; Carballo, Luis Fernando; Navarro, Marc; Nacher, Víctor; Sánchez, Francisco Miguel; Latorre, Rafael

    2015-01-01

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

  7. Excised porcine skin experimental systems to validate quantitative microdialysis methods for determination of drugs in skin after topical application.

    PubMed

    Seki, Toshinobu; Wang, Aiping; Yuan, Dan; Saso, Yuko; Hosoya, Osamu; Chono, Sumio; Morimoto, Kazuhiro

    2004-11-24

    Microdialysis is useful as a method to evaluate the disposition of drugs in the skin to design improved transdermal delivery systems (TDDSs). In this study, quantitative microdialysis methods were validated in excised porcine skin experimental systems in vitro. Flurbiprofen (FP), used as a model drug, showed high affinity for the skin tissues in equilibrium states between the medium and skin. The membrane clearances of FP for permeation through the membrane of a dialysis fiber placed in the skin (CL(m in S)) were lower than that in the medium. The adsorption of components in the skin to the membrane surface of the dialysis fiber and accumulation of FP near the dialysis fiber are the most likely reasons for this. When CL(m in S) was used to predict the extracellular FP concentration in skin (C(T)), the value obtained was lower than that expected from the FP concentration in the medium on the dermis side, which should be equal to C(T) at equilibrium. In the zero net flux (ZNF) method, in which the concentration difference of perfusate (DeltaC) between the inflow and outflow were used to obtain C(T), the predicted C(T) was similar to the expected value. In an in vitro skin permeation experiment, the ZNF method was used for the prediction of C(T) near the dialysis fiber. The predicted C(T) was over 10 times higher than the FP concentration in the medium on the dermis side, suggesting a concentration gradient in the dermis. Although the ZNF method is good for predicting the C(T) in skin, the mass balance has to be considered for the quantitative evaluation of the skin permeation of drugs. In this study, the effect of the mass transfer of FP from the perfusate to the skin on the cumulative amount of FP passing through the skin was relatively low because of the use of suitable solutions as perfusate. The perfusion conditions and schedules should be designed carefully for quantitative evaluations using the ZNF method. These results provide useful information for the in

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

    PubMed

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

    2015-11-15

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

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

    PubMed Central

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

    2015-01-01

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

  10. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  11. Constitutive Modeling of Porcine Liver in Indentation Using 3D Ultrasound Imaging

    PubMed Central

    Jordan, P.; Socrate, S.; Zickler, T.E.; Howe, R.D.

    2009-01-01

    In this work we present an inverse finite-element modeling framework for constitutive modeling and parameter estimation of soft tissues using full-field volumetric deformation data obtained from 3D ultrasound. The finite-element model is coupled to full-field visual measurements by regularization springs attached at nodal locations. The free ends of the springs are displaced according to the locally estimated tissue motion and the normalized potential energy stored in all springs serves as a measure of model-experiment agreement for material parameter optimization. We demonstrate good accuracy of estimated parameters and consistent convergence properties on synthetically generated data. We present constitutive model selection and parameter estimation for perfused porcine liver in indentation and demonstrate that a quasilinear viscoelastic model with shear modulus relaxation offers good model-experiment agreement in terms of indenter displacement (0.19 mm RMS error) and tissue displacement field (0.97 mm RMS error). PMID:19627823

  12. In vivo porcine left atrial wall stress: Computational model.

    PubMed

    Di Martino, Elena S; Bellini, Chiara; Schwartzman, David S

    2011-10-13

    Most computational models of the heart have so far concentrated on the study of the left ventricle, mainly using simplified geometries. The same approach cannot be adopted to model the left atrium, whose irregular shape does not allow morphological simplifications. In addition, the deformation of the left atrium during the cardiac cycle strongly depends on the interaction with its surrounding structures. We present a procedure to generate a comprehensive computational model of the left atrium, including physiological loads (blood pressure), boundary conditions (pericardium, pulmonary veins and mitral valve annulus movement) and mechanical properties based on planar biaxial experiments. The model was able to accurately reproduce the in vivo dynamics of the left atrium during the passive portion of the cardiac cycle. A shift in time between the peak pressure and the maximum displacement of the mitral valve annulus allows the appendage to inflate and bend towards the ventricle before the pulling effect associated with the ventricle contraction takes place. The ventricular systole creates room for further expansion of the appendage, which gets in close contact with the pericardium. The temporal evolution of the volume in the atrial cavity as predicted by the finite element simulation matches the volume changes obtained from CT scans. The stress field computed at each time point shows remarkable spatial heterogeneity. In particular, high stress concentration occurs along the appendage rim and in the region surrounding the pulmonary veins. PMID:21907340

  13. [The isolated normothermic hemoperfused porcine leg as model for pharmacological and toxicological investigations

    PubMed

    Nogueira; Wagner; Riebeling; Klug

    1999-01-01

    In this short communication we present the isolated normothermic hemoperfused porcine leg as an alternative model for pharmacological and toxicological investigations. Both legs and blood were obtained at a slaughter house. Legs were connected to the perfusion apparatus Mediport Biotechnik and provided with room air and nutrients via a dialysis module over a seven hour period. The perfusion pressure, the perfusion flow, the response to noradrenergic stimuli, the glucose consumption influenced by insulin dosage and the absorption of estradiol were investigated. Once noradrenalin was given perfusion pressure increased as expected and dropped back to normal only a few minutes after administration. Moreover, in the legs treated with insulin, a glucose consumption was detected. Only the legs treated with estradiol showed an increasing concentration of estradiol in plasma throughout the experiment. From the results obtained, it can be concluded that the isolated normothermic hemoperfused porcine leg seems to be a suitable alternative model for the testing of transdermal absorption as well as for the investigation of acute vasoactive substances. Further studies will be performed in our laboratory in order to determine the metabolic condition of this system as well as to ascertain other possibilities of this model in pharmacological and toxicological investigations. PMID:11107313

  14. Extrusion properties of porcine intestines and surrogate materials for ventral hernia modelling.

    PubMed

    Lyons, Mathew; Winter, Des C; Simms, Ciaran K

    2013-02-01

    A physical model of the abdomen can be a clean and cheap surrogate environment to assess new and existing closure solutions for post-laparoscopic wound closure, but a particular challenge is finding a surrogate material to replicate intestines which may protrude through a hernia. The literature shows no focus on this topic, and this paper therefore presents an investigation of the extrusion properties of fresh porcine intestines compared to a number of potential surrogate materials: silicone, edible gelatine, dough and reconstituted powdered potatoes (RPP). An extrusion rig was developed to simulate the mechanical environment of a post-operative hernia formation. Displacement controlled extrusion tests were performed, and the force-extrusion relationships at different extrusion velocities were compared for the intestines and the surrogate materials. The intestines showed a peak extrusion force ranging from 9 N to 14.8 N when pushed through a 13 mm hole, and similar extrusion properties between cleaned and uncleaned fresh porcine intestines were observed. The tests on surrogate materials showed that the surface tension properties of silicone gel resulted in high friction, that edible gelatine extruded like a liquid and that dough is very stiff, rendering all three materials unsuitable for use as surrogates. However, the RPP mix showed very similar force-extrusion properties compared to both the cleaned and uncleaned intestines. Viscoelastic testing (7.5 mm/min, 15 mm/min and 30 mm/min) showed little rate dependency in the extrusion properties for either the porcine intestines or the RPP. Despite the complexity of intestinal tissue and the obvious physical differences between intestine and RPP, it was found that there is no statistical difference between the yield strength of intestines and RPP (P values ranged between 0.14 and 0.3) at the rates tested.

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

    PubMed Central

    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 taken on day 0 at 10 minutes post burn and on day 8. Biopsies taken at day 0 revealed superficial to mid-dermal burns, with minimal dermal edema and necrosis. Those from day 8 showed mid to deep dermal edema and necrosis in all four test areas following a 20 second contact duration burn. The new contact burn device was able to create a consistent deep dermal burn after 20 seconds of contact. We anticipate that this new device could be used to investigate the development of hypertrophic scarring in a porcine model. PMID:27335694

  16. Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

    PubMed Central

    Weuster, Matthias; Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; van Griensven, Martijn; Witte, Ingo

    2015-01-01

    Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

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

    PubMed

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

    2015-08-15

    Human ocular Chlamydia trachomatis infections can lead to trachoma, the major cause of infectious blindness worldwide. Trachoma control strategies are very helpful but logistically challenging, and a trachoma vaccine is needed but not available. Pigs are a valuable large animal model for various immunological questions and could facilitate the study of human ocular chlamydial infections. In addition, a recent study identified the zoonotic potential of Chlamydia suis, the natural pathogen of pigs. In terms of the One Health Initiative, understanding the host-pathogen-interactions and finding a vaccine for porcine chlamydia infections would also benefit human health. Thus, we infected the porcine retinal cell line VIDO R1 with C. suis and analyzed the chlamydial life cycle and the innate immune response of the infected cells. Our results indicate that C. suis completes its life cycle in VIDO R1 cells within 48 h, comparable to C. trachomatis in humans. C. suis infection of VIDO R1 cells led to increased levels of various innate immune mediators like pathogen recognition receptors, cytokines and chemokines including IL6, TNFα, and MMP9, also most relevant in human C. trachomatis infections. These results illustrate the first steps in the host-pathogen-interactions of ocular C. suis infections in pigs and show their similarity to C. trachomatis infections in humans, justifying further testing of pigs as an animal model for human trachoma. PMID:26103808

  18. An Ex Vivo Porcine Nasal Mucosa Explants Model to Study MRSA Colonization

    PubMed Central

    Tulinski, Pawel; Fluit, Ad C.; van Putten, Jos P. M.; de Bruin, Alain; Glorieux, Sarah; Wagenaar, Jaap A.; Duim, Birgitta

    2013-01-01

    Staphylococcus aureus is an opportunistic pathogen able to colonize the upper respiratory tract and skin surfaces in mammals. Methicillin-resistant S. aureus ST398 is prevalent in pigs in Europe and North America. However, the mechanism of successful pig colonization by MRSA ST398 is poorly understood. To study MRSA colonization in pigs, an ex vivo model consisting of porcine nasal mucosa explants cultured at an air-liquid interface was evaluated. In cultured mucosa explants from the surfaces of the ventral turbinates and septum of the pig nose no changes in cell morphology and viability were observed up to 72 h. MRSA colonization on the explants was evaluated followed for three MRSA ST398 isolates for 180 minutes. The explants were incubated with 3×108 CFU/ml in PBS for 2 h to allow bacteria to adhere to the explants surface. Next the explants were washed and in the first 30 minutes post adhering time, a decline in the number of CFU was observed for all MRSA. Subsequently, the isolates showed either: bacterial growth, no growth, or a further reduction in bacterial numbers. The MRSA were either localized as clusters between the cilia or as single bacteria on the cilia surface. No morphological changes in the epithelium layer were observed during the incubation with MRSA. We conclude that porcine nasal mucosa explants are a valuable ex vivo model to unravel the interaction of MRSA with nasal tissue. PMID:23326505

  19. Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction

    PubMed Central

    Regueiro-Purriños, Marta; Fernández-Vázquez, Felipe; de Prado, Armando Perez; Altónaga, Jose R; Cuellas-Ramón, Carlos; Ajenjo-Silverio, Jose M; Orden, Asuncion; Gonzalo-Orden, Jose M

    2011-01-01

    Ischemia of the myocardium can lead to reversible or irreversible injury depending on the severity and duration of the preceding ischemia. Here we compared sevoflurane and isoflurane with particular reference to their hemodynamic effects and ability to modify the effects of acute severe myocardial ischemia and reperfusion on ventricular arrhythmias and mortality in a porcine model of myocardial infarction. Female Large White pigs were premedicated with ketamine, midazolam, and atropine. Propofol was given intravenously for the anesthetic induction, and anesthesia was maintained with isoflurane or sevoflurane. Endovascular, fluoroscopy-guided, coronary procedures were performed to occlude the midleft anterior descending artery by using a coronary angioplasty balloon. After 75 min, the balloon catheter system was withdrawn and the presence of adequate reperfusion flow was verified. The pigs were followed for 2 mo, and overall mortality rate was calculated. The isoflurane group showed lower arterial pressure throughout the procedure, with the difference reaching statistical significance after induction of myocardial ischemia. The ventricular fibrillation rate was higher in isoflurane group (81.3%) than the sevoflurane group (51.7%; relative risk, 1.57 [1.03 to 2.4]). Overall survival was lower in the isoflurane group (75%) than the sevoflurane group (96.4%). In conclusion, in this porcine model of myocardial ischemia and reperfusion, sevoflurane was associated with higher hemodynamic stability and fewer ventricular arrhythmias and mortality than was isoflurane. PMID:21333167

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

    PubMed

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

    2015-08-15

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

  1. Experimental infection of conventional nursing pigs and their dams with Porcine deltacoronavirus.

    PubMed

    Vitosh-Sillman, Sarah; Loy, John Dustin; Brodersen, Bruce; Kelling, Clayton; Doster, Alan; Topliff, Christina; Nelson, Eric; Bai, Jianfa; Schirtzinger, Erin; Poulsen, Elizabeth; Meadors, Barbara; Anderson, Joseph; Hause, Benjamin; Anderson, Gary; Hesse, Richard

    2016-09-01

    Porcine deltacoronavirus (PDCoV) is a newly identified virus that has been detected in swine herds of North America associated with enteric disease. The aim of this study was to demonstrate the pathogenicity, course of infection, virus kinetics, and aerosol transmission of PDCoV using 87 conventional piglets and their 9 dams, including aerosol and contact controls to emulate field conditions. Piglets 2-4 days of age and their dams were administered an oronasal PDCoV inoculum with a quantitative real-time reverse transcription (qRT)-PCR quantification cycle (Cq) value of 22 that was generated from a field sample having 100% nucleotide identity to USA/Illinois121/2014 determined by metagenomic sequencing and testing negative for other enteric disease agents using standard assays. Serial samples of blood, serum, oral fluids, nasal and fecal swabs, and tissues from sequential autopsy, conducted daily on days 1-8 and regular intervals thereafter, were collected throughout the 42-day study for qRT-PCR, histopathology, and immunohistochemistry. Diarrhea developed in all inoculated and contact control pigs, including dams, by 2 days post-inoculation (dpi) and in aerosol control pigs and dams by 3-4 dpi, with resolution occurring by 12 dpi. Mild to severe atrophic enteritis with PDCoV antigen staining was observed in the small intestine of affected piglets from 2 to 8 dpi. Mesenteric lymph node and small intestine were the primary sites of antigen detection by immunohistochemistry, and virus RNA was detected in these tissues to the end of the study. Virus RNA was detectable in piglet fecal swabs to 21 dpi, and dams to 14-35 dpi. PMID:27578872

  2. C-reactive protein, haptoglobin and Pig-Major acute phase protein profiles of pigs infected experimentally by different isolates of porcine reproductive and respiratory syndrome virus.

    PubMed

    Saco, Y; Martínez-Lobo, F; Cortey, M; Pato, R; Peña, R; Segalés, J; Prieto, C; Bassols, A

    2016-02-01

    Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiologic agent of PRRS, one of the most important diseases in swine worldwide. In the present work, the effects of different PRRSV strains were tested on a piglet experimental model to study the induced acute phase response. For this purpose, pigs (n=15 for each group) were intranasally inoculated with one of five PRRSV strains (isolates EU10, 12, 17, 18 from genotype 1 and isolate JA-142 from genotype 2). The acute phase response was monitored by measuring acute phase proteins (APPs). Specifically, the serum concentration of haptoglobin (Hp), C-reactive protein (CRP) and Pig-Major Acute Protein (Pig-MAP) was determined at 0, 3, 6, 9, 12, 15, 18 and 21 days p.i. Clinical signs and growth performance were also monitored during the experiment. All animals became viremic after inoculation during the study period. The APP response was heterogeneous and dependent on the strain, being strains EU10, EU 18 and JA-142 those that induced the highest response and the strongest clinical signs. In general, Hp was the most sensitive biomarker for PRRSV infection, CRP behaved as moderate and Pig-MAP was the less responsive during the course of PRRSV experimental infection. Hp and CRP were significantly discriminatory between infected and control pigs, but not Pig-MAP.

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

    PubMed Central

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

    2016-01-01

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

  4. Scabies Mites Alter the Skin Microbiome and Promote Growth of Opportunistic Pathogens in a Porcine Model

    PubMed Central

    Swe, Pearl M.; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja

    2014-01-01

    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/Significance This is the first

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

    PubMed Central

    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

  6. An Immunomodulatory Device Improves Insulin Resistance in Obese Porcine Model of Metabolic Syndrome

    PubMed Central

    Westover, Angela J.

    2016-01-01

    Obesity is associated with tissue inflammation which is a crucial etiology of insulin resistance. This inflammation centers around circulating monocytes which form proinflammatory adipose tissue macrophages (ATM). Specific approaches targeting monocytes/ATM may improve insulin resistance without the adverse side effects of generalized immunosuppression. In this regard, a biomimetic membrane leukocyte processing device, called the selective cytopheretic device (SCD), was evaluated in an Ossabaw miniature swine model of insulin resistance with metabolic syndrome. Treatment with the SCD in this porcine model demonstrated a decline in circulating neutrophil activation parameters and monocyte counts. These changes were associated with improvements in insulin resistance as determined with intravenous glucose tolerance testing. These improvements were also reflected in lowering of homeostatic model assessment- (HOMA-) insulin resistant (IR) scores for up to 2 weeks after SCD therapy. These results allow for the planning of first-in-man studies in obese type 2 diabetic patients.

  7. Efficacy of a new bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae (Fostera™ PCV MH) under experimental conditions.

    PubMed

    Park, Changhoon; Jeong, Jiwoon; Choi, Kyuhyung; Chae, Chanhee

    2016-01-01

    The objective of this study was to evaluate the efficacy of a new bivalent vaccine (Fostera™ PCV MH, Zoetis) of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae in growing pigs under experimental conditions. A total of 80 pigs were randomly divided into 8 groups (10 pigs per group). The pigs were administered the bivalent vaccine intramuscularly as a 2.0 mL dose at 21 days of age based on the manufacturer's instructions. Three weeks after vaccination, the pigs were inoculated with either PCV2 (intranasal route) or M. hyopneumoniae (intratracheal route) or both. Regardless of the type of inoculation, vaccinated pigs after challenge exhibited effective reduction of clinical signs, PCV2 viremia levels and mycoplasma nasal shedding, and lung and lymphoid lesion when compared to unvaccinated challenged pigs. Vaccinated challenged pigs had significantly higher (P<0.05) levels of PCV2-specific neutralizing antibodies, and numbers of PCV2-and M. hyopneumoniae-specific interferon-γ secreting cells compared to unvaccinated challenged pigs. This study demonstrates that the bivalent vaccine is able to protect pigs against either PCV2 or M. hyopneumoniae infection or both based on clinical, microbiological, immunological, and pathological evaluation. PMID:26626212

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

    PubMed

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

    2013-04-01

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

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

    PubMed Central

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

    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 were fed mainly bovine colostrum before weaning; after weaning, 6 were fed a starter diet containing 20% (w/w) bovine colostrum powder (STARTER-COL), and the other 6 were fed a starter diet without any bovine colostrum (STARTER-CTRL) until termination (day 42 or day 49). In experiment 1 the COL pigs had significantly fewer fever-days than did the RPL pigs. In experiment 2 diarrhea, typhlocolitis, and pancreatic degeneration developed in 4 of the STARTER-COL pigs after weaning. In both experiments all the pigs fed mainly bovine colostrum before weaning survived until termination. All pigs tested free of swine influenza virus H1N1 and H3N2, Porcine reproductive and respiratory syndrome virus, and Porcine parvovirus. In experiment 2 all the pigs tested free of Porcine circovirus type 2 (PCV2), but some in both groups tested positive for Torque teno virus genogroups 1 and 2. In conclusion, with the use of snatch-farrowing and bovine colostrum, pigs can be raised in the absence of porcine maternal antibodies with 100% survival and freedom from most porcine pathogens of biologic relevance. This model is potentially suitable for animal disease research. PMID:24082397

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

    PubMed

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

    2015-03-21

    Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery. Fluorescently stained, soluble Actrapid insulin was placed on the surface of human skin-mimicking materials subjected to 265 kHz, 10% duty cycle focused ultrasound. A confocally and coaxially aligned 5 MHz broadband ultrasound transducer was used to detect cavitation. Two different skin models were used. The first model, 3% agar hydrogel, was insonated with a range of pressures (0.25-1.40 MPa peak rarefactional focal pressure-PRFP), with and without cavitation nuclei embedded within the agar at a concentration of 0.05% w/v. The second, porcine skin was insonated at 1.00 and 1.40 MPa PRFP. In both models, fluorescence measurements were used to determine penetration depth and concentration of delivered insulin. Results show that in agar gel, both insulin penetration depth and concentration only increased significantly in the presence of inertial cavitation, with up to a 40% enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ultrasound compared to the control samples, but there was no significant increase in penetration distance. The results underline the importance of instigating and monitoring inertial cavitation during transdermal insulin delivery. PMID:25716689

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2015-03-21

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

  13. Microparticulate ICE slurry for renal hypothermia: laparoscopic partial nephrectomy in a porcine model.

    SciTech Connect

    Shikanov, S; Wille, M; Large, M; Razmaria, A; Lifshitz, D; Chang, A; Wu, Y; Kasza, K; Shalhav, A

    2010-10-01

    Previously, we described the feasibility of renal hypothermia using microparticulate ice slurry during laparoscopy. In the present study, we compared surface cooling with the ice slurry versus near-frozen saline or warm ischemia (WI) during laparoscopic partial nephrectomy (LPN) in a porcine model. We used a single-kidney porcine model. Animals in 5 equal groups (n = 6 each) underwent right laparoscopic complete nephrectomy. In Phase I, left LPN was performed under 90 minutes of ischemia and 90-minute renal cooling with either slurry (Slurry group 1) or saline (Saline group 1). No cooling was applied in the WI group. In Phase II, to simulate more extreme condition, ischemia time was extended to 120 minutes and cooling shortened to 10 minutes (Slurry group 2 and Saline group 2). The study endpoints were renal and core temperature during the surgery and serum creatinine at baseline and days 1, 3, 7, and 14 after the procedure. The ice slurry was easily produced and delivered. Nadir renal temperature (mean {+-} SD) was 8 {+-} 4 C in Slurry group 1 vs. 22.5 {+-} 3 C in Saline group 1 (P < .0001). Renal rewarming to 30 C occurred after 61 {+-} 7 minutes in Slurry group 2 vs. 24 {+-} 6 minutes in Saline group 2 (P < .0001). Core temperature decreased on average to 35 C in the Saline groups compared with 37 C in the Slurry groups (P < .0001). Serum creatinine did not differ between the Saline and Slurry groups in Phases I and II at any time point. Ice slurry provides superior renal cooling compared with near-frozen saline during LPN without associated core hypothermia.

  14. Bovine Serum Albumin Glutaraldehyde for Completely Sutureless Laparoscopic Heminephrectomy in a Survival Porcine Model

    PubMed Central

    Gamboa, Aldrin Joseph R.; Kaplan, Adam G.; Khosravi, Amanda; Truong, Hung; Andrade, Lorena; Lin, Rachelle; Alipanah, Reza; Ortiz, Cervando; McCormick, David; Box, Geoffrey N.; Lee, Hak J.; Deane, Leslie A.; Edwards, Robert A.; McDougall, Elspeth M.; Clayman, Ralph V.

    2010-01-01

    Abstract Introduction Laparoscopic partial nephrectomy (LPN) has not received widespread clinical application because of its technical challenge. Bovine serum albumin glutaraldehyde (BSAG) is a hemostatic agent that is independent of the clotting cascade. We evaluated the use of BSAG as the sole agent for parenchymal and collecting system closure during LPN in a survival porcine model. Methods Eighteen pigs underwent hilar clamping and LPN by longitudinal excision of the lateral one-third of the right kidney. The opened collecting system was covered with oxidized cellulose to prevent BSAG seepage into the urinary tract. BSAG was allowed to set for 10 or 5 minutes. Twelve animals underwent survival LPN BSAG only closure; six control pigs were acutely studied using saline. Urinary extravasation was evaluated by injection of furosemide and indigo carmine, and then evaluating the renal surface and bladder catheter drainage for dye. A subjective bleeding score was assigned after hilum unclamping. At 6 weeks, BSAG kidneys were harvested for burst pressure testing and histopathological analysis. Results All 12 pigs survived for 6 weeks. No pigs had urinary extravasation. Mean percentage of kidney removed by weight was 19%. Mean warm ischemia time was 29 minutes. Five pigs required a second BSAG application to achieve a bleeding score of 0. Mean arterial and collecting system burst pressures were 301.8 and 322.4 mm Hg, respectively. Mean postoperative creatinine increase was 0.07 mg/dL. Conclusion BSAG for completely sutureless LPN in a survival porcine model was feasible. PMID:20059350

  15. The effect of whole-body resonance vibration in a porcine model of spinal cord injury.

    PubMed

    Streijger, Femke; Lee, Jae H T; Chak, Jason; Dressler, Dan; Manouchehri, Neda; Okon, Elena B; Anderson, Lisa M; Melnyk, Angela D; Cripton, Peter A; Kwon, Brian K

    2015-06-15

    Whole-body vibration has been identified as a potential stressor to spinal cord injury (SCI) patients during pre-hospital transportation. However, the effect that such vibration has on the acutely injured spinal cord is largely unknown, particularly in the frequency domain of 5 Hz in which resonance of the spine occurs. The objective of the study was to investigate the consequences of resonance vibration on the injured spinal cord. Using our previously characterized porcine model of SCI, we subjected animals to resonance vibration (5.7±0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function was assessed weekly and cerebrospinal fluid (CSF) samples were collected to assess different inflammatory and injury severity markers. Spinal cords were evaluated histologically to quantify preserved white and gray matter. No significant differences were found between groups for CSF levels of monocyte chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic protein levels were lower in the resonance vibration group, compared with the non-vibrated control group. Spared white matter tissue was increased within the vibrated group at 7 d post-injury but this difference was not apparent at the 12-week time-point. No significant difference was observed in locomotor recovery following resonance vibration of the spine. Here, we demonstrate that exposure to resonance vibration for 1.5 or 3 h following SCI in our porcine model is not detrimental to the functional or histological outcomes. Our observation that a 3.0-h period of vibration at resonance frequency induces modest histological improvement at one week post-injury warrants further study.

  16. Dynamic and Volumetric Variables Reliably Predict Fluid Responsiveness in a Porcine Model with Pleural Effusion

    PubMed Central

    Broch, Ole; Gruenewald, Matthias; Renner, Jochen; Meybohm, Patrick; Schöttler, Jan; Heß, Katharina; Steinfath, Markus; Bein, Berthold

    2013-01-01

    Background The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions. Methods Pigs were studied at baseline and after fluid loading with 8 ml kg−1 6% hydroxyethyl starch. After withdrawal of 8 ml kg−1 blood and induction of pleural effusion up to 50 ml kg−1 on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis. Results Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion. Conclusions In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness. PMID:23418546

  17. Endoscopic spray cryotherapy for genitourinary malignancies: safety and efficacy in a porcine model

    PubMed Central

    Power, Nicholas E.; Silberstein, Jonathan L.; Tarin, Tatum; Au, Joyce; Thorner, Daniel; Ezell, Paula; Monette, Sébastien; Fong, Yuman; Rusch, Valerie; Finley, David

    2013-01-01

    Objective: To examine the effects and safety of using endoscopic spray cryotherapy (ESC) on bladder, ureteral, and renal pelvis urothelium in a live porcine model. Subjects and methods: ESC treatments were systematically applied to urothelial sites in the bladder, ureter, and renal pelvis of eight female Yorkshire swine in a prospective trial. Freeze–thaw cycles ranged from 5 to 60 s/cycle for one to six cycles using a 7 French cryotherapy catheter. Tissue was evaluated histologically for treatment-related effects. Acute physiologic effects were evaluated with pulse oximetry, Doppler sonography, and postmortem findings. Results: In bladder, treatment depth was inconsistent regardless of dose, demonstrating urothelial necrosis in one, muscularis propria depth necrosis in two, and full thickness necrosis in all remaining samples. In ureter, full thickness necrosis was seen in all samples, even with the shortest spray duration (5 s/cycle for six cycles or 30 s/cycle for one cycle). Treatment to the renal pelvis was complicated by adiabatic gas expansion of liquid nitrogen to its gaseous state, resulting in high intraluminal pressures requiring venting to avoid organ perforation, even at the lowest treatment settings. At a planned dose of 5 s/cycle for six cycles of the first renal pelvis animal, treatment was interrupted by sudden and unrecoverable cardiopulmonary failure after three cycles. Repeated studies replicated this event. Ultrasound and immediate necropsy confirmed the creation of a large gaseous embolism and reproducible cardiopulmonary effects. Conclusion: ESC in a porcine urothelial treatment model results in full-thickness tissue necrosis in bladder, ureter, and renal pelvis at a minimal treatment settings of 5 s/cycle for six cycles. Adiabatic gas expansion may result in fatal pyelovenous gas embolism and collateral organ injury, as seen in both animals receiving treatment to the renal pelvis in this study. These results raise safety concerns for use

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

    PubMed

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

    2016-03-01

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

  19. The History and Evolution of Experimental Traumatic Brain Injury Models.

    PubMed

    Povlishock, John

    2016-01-01

    This narrative provides a brief history of experimental animal model development for the study of traumatic brain injury. It draws upon a relatively rich history of early animal modeling that employed higher order animals to assess concussive brain injury while exploring the importance of head movement versus stabilization in evaluating the animal's response to injury. These themes are extended to the development of angular/rotational acceleration/deceleration models that also exploited brain movement to generate both the morbidity and pathology typically associated with human traumatic brain injury. Despite the significance of these early model systems, their limitations and overall practicality are discussed. Consideration is given to more contemporary rodent animal models that replicate individual/specific features of human injury, while via various transgenic technologies permitting the evaluation of injury-mediated pathways. The narrative closes on a reconsideration of higher order, porcine animal models of injury and their implication for preclinical/translational research. PMID:27604709

  20. Three dimensional electromechanical model of porcine heart with penetrating wound injury.

    PubMed

    Usyk, Taras; Kerckhoffs, Roy

    2005-01-01

    The aim of this study is development a prototype computational model of the pig heart that can be used to predict physiological responses to a penetrating wound injury. The pig has been chosen for this model studies because it shares many anatomical similarities with humans. Three-dimensional cubic Hermite finite element meshes based on detailed measurements of porcine anatomy combined into an integrated anatomic model. The pig ventricular model includes detailed left and right ventricular geometry and myofiber and laminar sheet orientations throughout the mesh. The cardiac mesh was refined and monodomain equations for action potential propagation solved using well-established collocation-Galerkin finite element methods. The membrane kinetic equations for the action potential model was based on detailed cellular models of transmembrane ionic fluxes and intracellular calcium fluxes in canine ventricular myocytes and human atrial myocytes. We modified the anisotropic myocardial conductivity tensor on the endocardial surface of the ventricles by making use of a surface model fitted to measured of Purkinje fiber network anatomy. The mechanical model compute regional three-dimensional stress and strain distributions using anisotropic constitutive laws referred to local material coordinate axes defined by local myofiber and laminar sheet orientations. Passive myocardial mechanics modeled using exponential orthotropic strain energy functions. Active systolic myocardial stresses computed from a multi-scale model that uses crossbridge theory to predict calcium-activated sarcomere length- and velocity-dependent tension filament tension. Since the electrical and mechanical models use a common finite element mesh as the parent parametric framework and both models are solved within our custom finite element package, it is straightforward to couple these models, as we have recently done for a model of coupled ventricular electromechanics. We apply the coupled electromechanical

  1. Purinergic P2X3 heteroreceptors enhance parasympathetic motor drive in isolated porcine detrusor, a reliable model for development of P2X selective blockers for detrusor hyperactivity.

    PubMed

    D'Agostino, Gianluigi; Condino, Anna Maria; Calvi, Valentina; Boschi, Federica; Gioglio, Luciana; Barbieri, Annalisa

    2012-01-01

    Various forms of low urinary tract symptoms (LUTS) seem dependant upon dysregulation of the purinergic pathway which produces sensory- or motor-activated incontinence. A body of evidence in human urinary bladders supports a link between up-regulation of purinergic activity and the pathogenesis of detrusor instability. This study investigated the potential role of adenosine 5'-triphosphate (ATP) in the control of detrusor motor drive in a model of porcine urinary bladder. The involvement of ATP on excitatory activity was assessed by measuring neurally-evoked [(3)H]-acetylcholine (ACh) release and smooth muscle contraction in detrusor strips. Epithelium-deprived preparations were used to minimize the influence of non-neural sources of ACh and ATP on parasympathetic neurotransmission. ACh release and smooth muscle contractility were not significantly affected by neural ATP in normal detrusor, but markedly enhanced when ATP hydrolysis was reduced by ectoATPase inhibitors, as well as by α,β-methylene-ATP (ABMA), agonist resistant to ecto-enzymes degradation. Prejunctional P2X receptors located on cholinergic nerves are involved in such potentiating effect. These purinergic heteroreceptors were characterized as P2X(3) subunits by means of the putative antagonists: NF449 (P2X(1,3) selective), NF023 (P2X(1,3) selective), PPNDS (P2X(1) selective) and A-317491 (P2X(3) selective). In porcine detrusor, P2X(3) receptors are functionally expressed at neural site facilitating neurogenic ACh release. When purine breakdown is experimentally down-regulated to mimicking the impaired purinergic pathway observed in pathological human bladders, endogenous ATP can markedly enhance detrusor contractility through activation of these receptors. Since P2X(3) blockade represents a potential therapeutic approach for diseases of the urinary tract, isolated porcine detrusor represents a reliable model for development of novel selective P2X(3) antagonists beneficial in the treatment of detrusor

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

    PubMed Central

    Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.

    2015-01-01

    Background 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. Methods 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. Results 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

  3. The Effect of Experimental Fusarium Mycotoxicosis on Microbiota Diversity in Porcine Ascending Colon Contents

    PubMed Central

    Piotrowska, Małgorzata; Śliżewska, Katarzyna; Nowak, Adriana; Zielonka, Łukasz; Żakowska, Zofia; Gajęcka, Magdalena; Gajęcki, Maciej

    2014-01-01

    The objective of the study was to determine the effect of exposure of pigs to the Fusarium mycotoxins zearalenone (ZEN) and deoxynivalenol (DON), administered together and separately, on the colon microbiota. An experiment was conducted for 42 days on gilts, randomly assigned to four groups and administered either ZEN, DON, ZEN+DON, or a placebo. The number of aerobic mesophilic bacteria, yeasts, molds, anaerobic Clostridium perfringens, fecal streptococci, Enterobacteriaceae, Escherichia coli, and lactic acid bacteria (LAB) were determined in the contents of the ascending colon. The influence of mycotoxins on the functional diversity of the colonic microbiota was assessed using EcoPlate tests (Biolog). Analysis revealed the predominance of LAB in all groups of pigs. Zearalenone, administered separately and together with DON, was found to have an adverse effect on mesophilic aerobic bacteria, but only after long exposure to this mycotoxin. During the six weeks of the experiment, the concentration of C. perfringens, E. coli, and other bacteria in the family Enterobacteriaceae was most considerably reduced in the experimental groups exposed to zearalenone, both separately and together with DON. Mycotoxins also affected the functional biodiversity of microorganisms. Both Shannon’s diversity index and the number of catabolized substrates in Biolog plate (the R index) were much higher in the group subjected to mixed mycotoxicosis. PMID:25025709

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

    SciTech Connect

    Muehlenbruch, Georg Nikoubashman, Omid; Steffen, Bjoern; Dadak, Mete; Palmowski, Moritz; Wiesmann, Martin

    2013-02-15

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

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

    PubMed Central

    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

  6. Validation of a realistic, simple, and inexpensive EUS-FNA training model using isolated porcine stomach

    PubMed Central

    Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Yoshida, Yoshitsugu; Abe, Yoko; Imbe, Koh

    2016-01-01

    Background and study aims: Trainees are required to learn EUS-FNA using a model before working with a patient. The aim of the current study was to validate a new training model developed for EUS-FNA. Patients and methods: Several fresh chicken tenderloins were embedded as target lesions in the submucosal layer of an isolated porcine stomach. The stomach was fixed to a plate with nails, and was placed in a tub filled with water. The primary endpoint was feasibility of the newly developed model for EUS-FNA training, evaluated as follows: 1) visualization of the target lesion with blinding for lesion location; 2) penetrability of the needle; 3) sampling rate of macroscopic specimen; and 4) ROSE capability. Secondary endpoints were its durability and utility for multiple EUS-FNA procedures during EUS-FNA training, and the ease and cost of preparing the model. Results: Six endoscopists (1 expert, 5 trainees) attempted EUS-FNA procedures using this model. The target lesion could be identified clearly, and EUS-FNA could be performed with realistic resistance felt. In addition, rapid on-site evaluation could be easily achieved. Based on 10 needlings by each endoscopist, adequate specimens for histology could be macroscopically taken with an average 85 % success rate. Visibility and maneuverability were maintained throughout all needlings. Preparation time for this model was less than 30 minutes with a total cost of $ 22. Conclusions: An easy-to-use and inexpensive training model with a realistic feel of needling was created. This model can potentially enable beginners to practice safe and effective EUS-FNA procedures. PMID:27652292

  7. Validation of a realistic, simple, and inexpensive EUS-FNA training model using isolated porcine stomach

    PubMed Central

    Hoshi, Koki; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Igarashi, Ryo; Yoshida, Yoshitsugu; Abe, Yoko; Imbe, Koh

    2016-01-01

    Background and study aims: Trainees are required to learn EUS-FNA using a model before working with a patient. The aim of the current study was to validate a new training model developed for EUS-FNA. Patients and methods: Several fresh chicken tenderloins were embedded as target lesions in the submucosal layer of an isolated porcine stomach. The stomach was fixed to a plate with nails, and was placed in a tub filled with water. The primary endpoint was feasibility of the newly developed model for EUS-FNA training, evaluated as follows: 1) visualization of the target lesion with blinding for lesion location; 2) penetrability of the needle; 3) sampling rate of macroscopic specimen; and 4) ROSE capability. Secondary endpoints were its durability and utility for multiple EUS-FNA procedures during EUS-FNA training, and the ease and cost of preparing the model. Results: Six endoscopists (1 expert, 5 trainees) attempted EUS-FNA procedures using this model. The target lesion could be identified clearly, and EUS-FNA could be performed with realistic resistance felt. In addition, rapid on-site evaluation could be easily achieved. Based on 10 needlings by each endoscopist, adequate specimens for histology could be macroscopically taken with an average 85 % success rate. Visibility and maneuverability were maintained throughout all needlings. Preparation time for this model was less than 30 minutes with a total cost of $ 22. Conclusions: An easy-to-use and inexpensive training model with a realistic feel of needling was created. This model can potentially enable beginners to practice safe and effective EUS-FNA procedures.

  8. A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration.

    PubMed

    Cullen, D Kacy; Harris, James P; Browne, Kevin D; Wolf, John A; Duda, John E; Meaney, David F; Margulies, Susan S; Smith, Douglas H

    2016-01-01

    Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive non-impact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI. PMID:27604725

  9. Intracoronary photodynamic therapy reduces neointimal growth without suppressing re‐endothelialisation in a porcine model

    PubMed Central

    Waksman, R; Leitch, I M; Roessler, J; Yazdi, H; Seabron, R; Tio, F; Scott, R W; Grove, R I; Rychnovsky, S; Robinson, B; Pakala, R; Cheneau, E

    2006-01-01

    Objective To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis. Methods 28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n  =  19) or the stented group (n  =  9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm2) was applied to activate the drug (n  =  10). Control arteries (n  =  9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis. Results Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by ⩽ 60% and 50% within BI and stented arteries (3.43 (0.27) mm2v 5.51 (0.52) mm2, p < 0.05; 4.0 (0.02) mm2v 6.0 (0.16) mm2, p < 0.01), respectively. Complete re‐endothelialisation was observed by immunohistochemical and gross histological analyses in all PDT and control arteries. There were no cases of aneurysm formation or thrombosis. Conclusion Intracoronary PhotoPoint PDT with MV0611 reduces intimal proliferation without suppressing re‐endothelialisation in a porcine model of restenosis. PMID:16399853

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

    PubMed

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

    2015-10-01

    Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients. PMID:26358387

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

    PubMed

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

    2015-10-01

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

  12. Endoscopic ultrasonography-guided placement of a transhepatic portal vein stent in a live porcine model

    PubMed Central

    Park, Tae Young; Seo, Dong Wan; Kang, Hyeon-Ji; Cho, Min Keun; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

    2016-01-01

    Background and Objectives: Percutaneous portal vein (PV) stent placement is used to manage PV occlusion or stenosis caused by malignancy. The use of endoscopic ultrasonography (EUS) has expanded to include vascular interventions. The aim of this study was to examine the technical feasibility and safety of EUS-guided transhepatic PV stent placement in a live porcine model. Materials and Methods: EUS-guided transhepatic PV stent placement was performed in six male miniature pigs under general anesthesia using forward-viewing echoendoscope. Under EUS guidance, the left intrahepatic PV was punctured with a 19-gauge fine-needle aspiration (FNA) needle and a 0.025 inch guidewire inserted through the needle and into the main PV. The FNA needle was then withdrawn and a needle-knife inserted to dilate the tract. Under EUS and fluoroscopic guidance, a noncovered metal stent was inserted over the guidewire and released into the main PV. Results: A PV stent was placed successfully in all six pigs with no technical problems or complications. The patency of the stent in the main PV was confirmed using color Doppler EUS and transhepatic portal venography. Necropsy of the first three animals revealed no evidence of bleeding and damage to intra-abdominal organs or vessels. No complications occurred in the remaining three animals during the 8 weeks observation period. Conclusions: EUS-guided transhepatic PV stent placement can be both technically feasible and safe in a live animal model. PMID:27803904

  13. Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

    PubMed Central

    Stecher, David; Bronkers, Glenn; Noest, Jappe O.T.; Tulleken, Cornelis A.F.; Hoefer, Imo E.; van Herwerden, Lex A.; Pasterkamp, Gerard; Buijsrogge, Marc P.

    2014-01-01

    To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated. PMID:25490000

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

    PubMed Central

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

    2011-01-01

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

  15. A Triple Culture Model of the Blood-Brain Barrier Using Porcine Brain Endothelial cells, Astrocytes and Pericytes.

    PubMed

    Thomsen, Louiza Bohn; Burkhart, Annette; Moos, Torben

    2015-01-01

    In vitro blood-brain barrier (BBB) models based on primary brain endothelial cells (BECs) cultured as monoculture or in co-culture with primary astrocytes and pericytes are useful for studying many properties of the BBB. The BECs retain their expression of tight junction proteins and efflux transporters leading to high trans-endothelial electric resistance (TEER) and low passive paracellular permeability. The BECs, astrocytes and pericytes are often isolated from small rodents. Larger species as cows and pigs however, reveal a higher yield, are readily available and have a closer resemblance to humans, which make them favorable high-throughput sources for cellular isolation. The aim of the present study has been to determine if the preferable combination of purely porcine cells isolated from the 6 months old domestic pigs, i.e. porcine brain endothelial cells (PBECs) in co-culture with porcine astrocytes and pericytes, would compare with PBECs co-cultured with astrocytes and pericytes isolated from newborn rats with respect to TEER value and low passive permeability. The astrocytes and pericytes were grown both as contact and non-contact co-cultures as well as in triple culture to examine their effects on the PBECs for barrier formation as revealed by TEER, passive permeability, and expression patterns of tight junction proteins, efflux transporters and the transferrin receptor. This syngenic porcine in vitro BBB model is comparable to triple cultures using PBECs, rat astrocytes and rat pericytes with respect to TEER formation, low passive permeability, and expression of hallmark proteins signifying the brain endothelium (tight junction proteins claudin 5 and occludin, the efflux transporters P-glycoprotein (PgP) and breast cancer related protein (BCRP), and the transferrin receptor).

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed

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

    2004-12-01

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

  18. Effects of Celox and TraumaDEX on hemorrhage control in a porcine model.

    PubMed

    Gegel, Brian T; Burgert, James M; Lockhart, Cheryl; Austin, Robert; Davila, Alejandro; Deeds, Jacob; Hodges, Lonnie; Hover, Andrew; Roy, John; Simpson, Glenn; Weaver, Stephen; Wolfe, William; Johnson, Don

    2010-04-01

    The purpose of this study was to compare the effectiveness of 2 hemostatic agents, chitosan-based Celox and the biopolymeric, microporous particles TraumaDEX, with a control group in a porcine model of hemorrhage. The animals were randomly assigned to 1 of 3 groups: Celox (n = 5), TraumaDEX (n = 5), or a standard pressure dressing alone (n = 5). To simulate a battlefield injury, the investigators generated a compound groin injury with transection of the femoral artery and vein in 15 pigs. After 1 minute of uncontrolled hemorrhage, Celox or TraumaDEX was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 minutes of direct manual pressure was applied to the wound, followed by a standard pressure dressing (3M Coban). After 30 minutes, dressings were removed, and the amount of bleeding was measured. There were statistically significant differences in bleeding between Celox and control (P = .01) and between TraumaDEX and control (P = .038), but no statistically significant difference in bleeding between Celox and TraumaDEX (P = .478). Celox and TraumaDEX may be effective hemostatic agents for use in civilian and military trauma.

  19. In vivo hyperspectral imaging of traumatic skin injuries in a porcine model

    NASA Astrophysics Data System (ADS)

    Randeberg, Lise L.; Winnem, Andreas M.; Larsen, Eivind L. P.; Haaverstad, Rune; Haugen, Olav A.; Svaasand, Lars O.

    2007-02-01

    Studies of immediate skin reactions are important to understand the underlying biological mechanisms involved in traumatic or chemical damage to the skin. In this study the spatial and spectral information provided by hyperspectral images was used to identify and characterize non-penetrating skin injuries in a porcine model. A hyperspectral imaging system (Hyspex, Norsk Elektro Optikk AS) was used to monitor the temporal development of minor skin injuries in an anesthetized Norwegian domestic pig. Hyperspectral data were collected in the wavelength range 400-1000 nm (VNIR), with a spectral sampling interval of 3.7 nm. The measurements were initiated immediately after inflicting the injury, and were repeated at least five times at each site with irregular frequency. The last measurement was performed 4 hours after injury. Punch biopsies (5 mm), were collected from adjacent normal skin, and at the center and the margin of each injury. The study was approved by the national animal research authority. The hyperspectral data were analyzed with respect to oxy- and deoxyhemoglobin, and erythema index. The skin biopsies were examined to determine the extent of skin damage in the bruised zones. Preliminary results show that hyperspectral imaging allows discrimination between traumatized skin and normal skin in an early phase. The extent and location of the hemorrhages can be determined from hyperspectral images. These findings might contribute to a better understanding of immediate skin reactions to minor trauma, and thereby the development of a better diagnostic modality for non-penetrating skin injuries in forensic medicine.

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

    NASA Astrophysics Data System (ADS)

    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%.

  1. Noncontact imaging of burn depth and extent in a porcine model using spatial frequency domain imaging

    PubMed Central

    Mazhar, Amaan; Saggese, Steve; Pollins, Alonda C.; Cardwell, Nancy L.; Nanney, Lillian; Cuccia, David J.

    2014-01-01

    Abstract. The standard of care for clinical assessment of burn severity and extent lacks a quantitative measurement. In this work, spatial frequency domain imaging (SFDI) was used to measure 48 thermal burns of graded severity (superficial partial, deep partial, and full thickness) in a porcine model. Functional (total hemoglobin and tissue oxygen saturation) and structural parameters (tissue scattering) derived from the SFDI measurements were monitored over 72 h for each burn type and compared to gold standard histological measurements of burn depth. Tissue oxygen saturation (stO2) and total hemoglobin (ctHbT) differentiated superficial partial thickness burns from more severe burn types after 2 and 72 h, respectively (p<0.01), but were unable to differentiate deep partial from full thickness wounds in the first 72 h. Tissue scattering parameters separated superficial burns from all burn types immediately after injury (p<0.01), and separated all three burn types from each other after 24 h (p<0.01). Tissue scattering parameters also showed a strong negative correlation to histological burn depth as measured by vimentin immunostain (r2>0.89). These results show promise for the use of SFDI-derived tissue scattering as a correlation to burn depth and the potential to assess burn depth via a combination of SFDI functional and structural parameters. PMID:25147961

  2. Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

    PubMed

    Ibuki, Masahisa; Fukui, Kensuke; Kanatani, Hiroyuki; Mine, Yoshinori

    2014-05-01

    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. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1β, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation.

  3. Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

    PubMed

    Ibuki, Masahisa; Fukui, Kensuke; Kanatani, Hiroyuki; Mine, Yoshinori

    2014-05-01

    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. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1β, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation. PMID:24430661

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

    PubMed

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

    2013-01-01

    Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and (2) Ventralight ST Mesh + transfascial sutures (TSs). Procedure time and mesh centering accuracy overtop of a simulated surgical defect were evaluated. Results. Echo PS demonstrated a 38.9% reduction in the overall procedure time, as compared to TS. During mesh preparation and positioning, Echo PS demonstrated a 60.5% reduction in procedure time (P < 0.0001). Although a trend toward improved centering accuracy was observed for Echo PS (16.2%), this was not significantly different than TS. Conclusions. Echo PS demonstrated a significant reduction in overall simulated LVHR procedure time, particularly during mesh preparation/positioning. These operative time savings may translate into reduced operating room costs and improved surgeon/operating room efficiency.

  5. Antibody Responses to Sarcoptes scabiei Apolipoprotein in a Porcine Model: Relevance to Immunodiagnosis of Recent Infection

    PubMed Central

    Rampton, Melanie; Walton, Shelley F.; Holt, Deborah C.; Pasay, Cielo; Kelly, Andrew; Currie, Bart J.; McCarthy, James S.; Mounsey, Kate E.

    2013-01-01

    No commercial immunodiagnostic tests for human scabies are currently available, and existing animal tests are not sufficiently sensitive. The recombinant Sarcoptes scabiei apolipoprotein antigen Sar s 14.3 is a promising immunodiagnostic, eliciting high levels of IgE and IgG in infected people. Limited data are available regarding the temporal development of antibodies to Sar s 14.3, an issue of relevance in terms of immunodiagnosis. We utilised a porcine model to prospectively compare specific antibody responses to a primary infestation by ELISA, to Sar s 14.3 and to S. scabiei whole mite antigen extract (WMA). Differences in the antibody profile between antigens were apparent, with Sar s 14.3 responses detected earlier, and declining significantly after peak infestation compared to WMA. Both antigens resulted in >90% diagnostic sensitivity from weeks 8–16 post infestation. These data provide important information on the temporal development of humoral immune responses in scabies and further supports the development of recombinant antigen based immunodiagnostic tests for recent scabies infestations. PMID:23762351

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

    PubMed Central

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

    2013-01-01

    Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and (2) Ventralight ST Mesh + transfascial sutures (TSs). Procedure time and mesh centering accuracy overtop of a simulated surgical defect were evaluated. Results. Echo PS demonstrated a 38.9% reduction in the overall procedure time, as compared to TS. During mesh preparation and positioning, Echo PS demonstrated a 60.5% reduction in procedure time (P < 0.0001). Although a trend toward improved centering accuracy was observed for Echo PS (16.2%), this was not significantly different than TS. Conclusions. Echo PS demonstrated a significant reduction in overall simulated LVHR procedure time, particularly during mesh preparation/positioning. These operative time savings may translate into reduced operating room costs and improved surgeon/operating room efficiency. PMID:23762628

  7. Experimental Models for Neurotrauma Research.

    PubMed

    Davidsson, Johan; Risling, Mårten

    2016-01-01

    Physical trauma in the central nervous system (CNS) is usually the result of a number of forces in different directions and dimensions. A large number of experimental models have been developed to improve the possibilities to understand the outcome of CNS trauma. In this chapter, we will describe the need for a variety of experimental models for research on traumatic brain injury (TBI) and spinal cord injury (SCI). Models can serve different needs, such as: to test new treatments for injuries, to reveal thresholds for injuries, to provide a better understanding of injury mechanisms, or to test tools and methods for translation between experiments and clinical data. In this chapter, we will discuss on the validation of models and translation between experimental and clinical studies. PMID:27604724

  8. Virtual Electrophysiologic Study in a Three-dimensional Cardiac MRI Model of Porcine Myocardial Infarction

    PubMed Central

    Ng, Jason; Jacobson, Jason T; Ng, Justin K; Gordon, David; Lee, Daniel C; Carr, James C.; Goldberger, Jeffrey J

    2012-01-01

    Objective This study sought to test the hypothesis that “virtual” electrophysiologic studies (EPS) on an anatomic platform generated by 3D MRI reconstruction of the left ventricle (LV) can reproduce the reentrant circuits of induced ventricular tachycardia (VT) in a porcine model of myocardial infarction (MI). Background Delayed-enhancement MRI has been used to characterize MI and “gray zones”, which are thought to reflect heterogeneous regions of viable and non-viable myocytes. Methods MI by coronary artery occlusion was induced in eight pigs. After a recovery period, 3D cardiac MRIs were obtained from each pig in-vivo. Normal areas, gray zones, and infarct cores were classified based on voxel intensity. In the computer model, gray zones were assigned slower conduction and longer action potential durations than those for normal myocardium. Virtual EPS was performed and was compared to results of actual in vivo programmed stimulation and non-contact mapping. Results The LV volumes ranged from 97.8 to 166.2 cm3 with 4.9 to 17.5% of voxels classified as infarct zones. Six of the seven pigs that developed VT during actual EPS were also inducible with virtual EPS. Four of the six pigs that had simulated VT had reentrant circuits that approximated the circuits seen with non-contact mapping, while the remaining two had similar circuits but propagating in opposite directions. Conclusions This initial study demonstrates the feasibility of applying a mathematical model to MRI reconstructions of the LV to predict VT circuits. Virtual EPS may be helpful to plan catheter ablation strategies or to identify patients who are at risk for future episodes of VT. PMID:22633654

  9. Diet-induced increase in plasma oxidized LDL promotes early fibrosis in a renal porcine auto-transplantation model

    PubMed Central

    2014-01-01

    Background In kidney transplantation, the prevalence of hypercholesterolemia as a co-morbidity factor known to affect graft function, is rising due to the increased number of older donors in response to organ shortage as well as to the hyperlipidemic effects of immunosuppressors in recipient. This study aimed to characterize the effects of hypercholesterolemia on renal graft outcome, investigating the role of oxidized low-density lipoprotein (OxLDL). Methods In vivo, we used a porcine preclinical model of renal auto-transplantation modulated by two experimental diets: a normal (n = 6) or a hyperlipidemic diet (n = 5) maintained during the 3 month follow-up after the surgical procedure. Kidney function and OxLDL levels were monitored as well as fibrosis, LOX-1 and TGF beta signaling pathways. In vitro, we used human artery endothelial cells subjected to OxLDL to investigate the TGF beta profibrotic pathway and the role of the scavenger receptor LOX-1. Results Hyperlipidemic diet-induced increase in plasma OxLDL levels at the time of surgery correlated with an increase in proteinuria 3 months after transplantation, associated with an early graft fibrosis combined with an activation of renal TGF beta signaling. These data suggest a direct involvement of OxLDL in the hyperlipidemic diet-induced activation of the pro-fibrotic TGF beta pathway which seems to be activated by LOX-1 signaling. These results were supported by studies with endothelial cells incubated in culture medium containing OxLDL promoting TGF beta expression inhibited by LOX-1 antibody. Conclusions These results implicate OxLDL in the hyperlipidemic diet-promoted fibrosis in transplanted kidneys, suggesting LOX-1 as a potential therapeutic target and reinforce the need to control cholesterol levels in kidney transplant recipients. PMID:24655356

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

    PubMed

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

    2010-08-01

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

  11. Remote Ischemic Preconditioning Reduces Cerebral Oxidative Stress Following Hypothermic Circulatory Arrest in a Porcine Model.

    PubMed

    Arvola, Oiva; Haapanen, Henri; Herajärvi, Johanna; Anttila, Tuomas; Puistola, Ulla; Karihtala, Peeter; Tuominen, Hannu; Anttila, Vesa; Juvonen, Tatu

    2016-01-01

    Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups. The study group underwent an intervention of 4 cycles of 5-minute ischemic preconditioning on the right hind leg. All piglets underwent 60-minute hypothermic circulatory arrest. Oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) was measured from blood samples with enzyme-linked immunosorbent assay. After 7 days of follow-up, samples from the brain, heart, kidney, and ovary were harvested for histopathologic examination. The immunohistochemical stainings of hypoxia marker hypoxia-inducible factor-1-α, oxidative stress marker 8-OHdG, DNA repair enzyme 8-oxoguanine glycosylase, and antioxidant response regulators nuclear factor erythroid 2-related factor 2 and protein deglycase were analyzed. The level of 8-OHdG referred to baseline was decreased in the sagittal sinus׳ blood samples in the study group after a prolonged deep hypothermic circulatory arrest at 360 minutes after reperfusion. Total histopathologic score was 3.8 (1.8-6.0) in the study group and was 4.4 (2.5-6.5) in the control group (P = 0.72), demonstrating no statistically significant difference in cerebral injury. Our findings demonstrate that the positive effects of remote ischemic preconditioning can be seen in cellular oxidative balance regulators in an animal model after 7 days of preconditioned ischemic insult. PMID:27568144

  12. Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model

    PubMed Central

    Pidial, Laetitia; Camilleri, Sophie; Bellucci, Alexandre; Casanova, Amaury; Viel, Thomas; Tavitian, Bertrand; Cellier, Christophe; Clement, Olivier

    2016-01-01

    Background & Aims Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. Methods Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. Results One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6(17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). Conclusion In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture’s rate. PMID:26930409

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Carbon dioxide laser ablation with immediate autografting in a full-thickness porcine burn model.

    PubMed Central

    Glatter, R D; Goldberg, J S; Schomacker, K T; Compton, C C; Flotte, T J; Bua, D P; Greaves, K W; Nishioka, N S; Sheridan, R L

    1998-01-01

    OBJECTIVE: To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply débrided wounds in a porcine model. SUMMARY BACKGROUND DATA: Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. METHODS: Full-thickness paravertebral burn wounds measuring 36 cm2 were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 microm of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. RESULTS: The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18+/-0.05 mm. The mean graft take was 96+/-11% in manual sites and 93+/-8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. CONCLUSIONS: Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome. Images Figure 1. Figure 2. Figure 3

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

    PubMed

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

    2008-10-01

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

  16. Tracheal and bronchial polymeric immunoglobulin secretory immune system (PISIS) development in a porcine model.

    PubMed

    Guzman-Bautista, E R; Ramirez-Estudillo, M C; Rojas-Gomez, O I; Vega-Lopez, M A

    2015-12-01

    Polymeric immunoglobulins (pIgs) mucosal secretion is mediated by the pIg secretory immune system (PISIS), which is composed of J-chain (JC) and antibody (IgM/IgA) producing cells (JC-AbPC), pIg receptor (pIgR) epithelial cell expression and the efficient release of secretory Igs (SIgs) to the mucosal lumen. A poor development or disturbances in this system may cause higher infection susceptibility, as observed in young and elderly people. In spite of this system's importance, few detailed studies regarding its development have been described in the lower respiratory tract of humans. Because the porcine model has been reported as an option for translational medicine to humans, we studied the tracheal and bronchial PISIS development in healthy, non-vaccinated, SPF, miniature Vietnamese pigs from birth to adulthood using immunohistochemistry and ELISAs. Our results demonstrated that pIgR was present at birth, and its expression increased with age. In contrast, JC-AbPC were low in neonatal pigs; however, colostrum was a source of IgM, SIgA, total IgA and IgG in respiratory secretions (trachea and bronchoalveolar lavages, nasal secretion and saliva) in piglets. JC-AbPC steadily increased in post-weaned, young and adult pigs, correlating with considerable increases in secretory and total Igs in the trachea and bronchi. These data suggest a compensatory role of maternal Igs at the respiratory mucosa in the absence of a structured PISIS before weaning. Furthermore, monomeric Igs (IgG and IgA) may also play an important role in respiratory protection and deserves a more thorough study. PMID:26188097

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

    SciTech Connect

    Choi, Jae Woong Lu, David S. K. Osuagwu, Ferdnand Raman, Steven; Lassman, Charles

    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.

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

    PubMed

    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 <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory 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.

  19. Small-Incision Laparoscopy-Assisted Surgery Under Abdominal Cavity Irrigation in a Porcine Model

    PubMed Central

    Ishii, Takuro; Aoe, Tomohiko; Yu, Wen-Wei; Ebihara, Yuma; Kawahira, Hiroshi; Isono, Shiro; Naya, Yukio

    2016-01-01

    Abstract Background: Laparoscopic and robot-assisted surgeries are performed under carbon dioxide insufflation. Switching from gas to an isotonic irrigant introduces several benefits and avoids some adverse effects of gas insufflation. We developed an irrigating device and apparatus designed for single-incision laparoscopic surgery and tested its advantages and drawbacks during surgery in a porcine model. Materials and Methods: Six pigs underwent surgical procedures under general anesthesia. A 30-cm extracorporeal cistern was placed over a 5–6-cm abdominal incision. The abdomen was irrigated with warm saline that was drained via a suction tube placed near the surgical field and continuously recirculated through a closed circuit equipped with a hemodialyzer as a filter. Irrigant samples from two pigs were cultured to check for bacterial and fungal contamination. Body weight was measured before and after surgery in four pigs that had not received treatments affecting hemodynamics or causing diuresis. Results: One-way flow of irrigant ensured laparoscopic vision by rinsing blood from the surgical field. Through a retroperitoneal approach, cystoprostatectomy was successfully performed in three pigs, nephrectomy in two, renal excision in two, and partial nephrectomy in one, under simultaneous ultrasonographic monitoring. Through a transperitoneal approach, liver excision and hemostasis with a bipolar sealing device were performed in three pigs, and bladder pedicle excision was performed in one pig. Bacterial and fungal contamination of the irrigant was observed on the draining side of the circuit, but the filter captured the contaminants. Body weight increased by a median of 2.1% (range, 1.2–4.4%) of initial weight after 3–5 hours of irrigation. Conclusions: Surgery under irrigation is feasible and practical when performed via a cistern through a small abdominal incision. This method is advantageous, especially in the enabling of continuous and free

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

    PubMed Central

    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

  1. Comparison of solvents for removing pesticides from skin using an in vitro porcine model.

    PubMed

    Campbell, J L; Smith, M A; Eiteman, M A; Williams, P L; Boeniger, M F

    2000-01-01

    This study compared four solvents (1-propanol, polyethylene glycol [avg. MW 400], 10% Ivory Liquid and water, and D-TAM) for their ability to remove selected pesticides from an in vitro porcine skin model using a solvent-moistened wipe. Wipes were performed 90 min after pesticide was applied to the skin. The four pesticides selected (glyphosate, alachlor, methyl parathion, and trifluralin) were chosen because of their differences in water solubility. This study also determined whether pretreatment of skin with a solvent prior to pesticide application would either increase or decrease recovery of the pesticide. Recovery efficiencies for all solvents and pesticides were affected by the amount of contaminant on the skin. Although pesticide recoveries from all four solvents were similar (range: 45-57%), on average 1-propanol had significantly higher recoveries, followed by soap and water. There was no significant difference between polyethylene glycol, and D-TAM. When skin was pretreated with any of the four solvents before pesticide application, the recoveries of the more water soluble compounds, glyphosate and alachlor, decreased. When pretreatment with solvent preceded application of trifluralin, the pesticide with the lowest water solubility, recoveries increased. 1-Propanol or soap and water were more effective in removing pesticides from skin than polyethylene glycol or D-TAM, but the amount of pesticide recovered from skin was affected by the chemical characteristics of the pesticide (such as water solubility) and the amount of pesticide originally on the skin. This study provides information useful to the interpretation of skin wipe sample results collected in field studies.

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

    PubMed

    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 (<24 h) form macroscopic (2-5 mm), compacted 3D hepatospheroid structures consisting of a shell of glycogen-positive viable cells circumscribing a core of eosinophilic cells. The spheroid shell layers exhibited ultrastructural, morphological and functional features of differentiated, polarized hepatic tissue including strong expression of the integrin alpha(5) subunit, functional bile canaliculi, albumin synthesis, and fine ultrastructure reminiscent of in vivo hepatic tissue. The low fluid shear 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

  3. Comparison of cold crystalloid and colloid infusions for induction of therapeutic hypothermia in a porcine model of cardiac arrest

    PubMed Central

    2013-01-01

    Introduction Large-volume cold intravenous infusion of crystalloids has been used for induction of therapeutic hypothermia after cardiac arrest. However, the effectiveness of cold colloids has not been evaluated. Therefore, we performed an experimental study to investigate the cooling effect of cold normal saline compared to colloid solution in a porcine model of ventricular fibrillation. Methods Ventricular fibrillation was induced for 15 minutes in 22 anesthetized domestic pigs. After spontaneous circulation was restored, the animals were randomized to receive either 45 ml/kg of 1°C cold normal saline (Group A, 9 animals); or 45 ml/kg of 1°C cold colloid solution (Voluven®, 6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) during 20 minutes (Group B, 9 animals); or to undergo no cooling intervention (Group C, 4 animals). Then, the animals were observed for 90 minutes. Cerebral, rectal, intramuscular, pulmonary artery, and subcutaneous fat body temperatures (BT) were recorded. In the mechanical ex-vivo sub study we added a same amount of cold normal saline or colloid into the bath of normal saline and calculated the area under the curve (AUC) for induced temperature changes. Results Animals treated with cold fluids achieved a significant decrease of BT at all measurement sites, whereas there was a consistent significant spontaneous increase in group C. At the time of completion of infusion, greater decrease in pulmonary artery BT and cerebral BT in group A compared to group B was detected (−2.1 ± 0.3 vs. -1.6 ± 0.2°C, and −1.7 ± 0.4 vs. -1.1 ± 0.3°C, p < 0.05, respectively). AUC analysis of the decrease of cerebral BT revealed a more vigorous cooling effect in group A compared to group B (−91 ± 22 vs. -68 ± 23°C/min, p = 0.046). In the mechanical sub study, AUC analysis of the induced temperature decrease of cooled solution revealed that addition of normal saline led to more intense cooling than colloid solution (

  4. Experimental analysis of the mechanical behavior of the viscoelastic porcine pancreas and preliminary case study on the human pancreas.

    PubMed

    Wex, C; Fröhlich, M; Brandstädter, K; Bruns, C; Stoll, A

    2015-01-01

    The aim of this article is to study the mechanical properties of the pancreas. Up to now, the mechanical properties of the pancreas are not sufficiently characterized. The possibility of intraoperative mechanical testing of pathological pancreata will allow the classification of pancreatic diseases in the future. The application of mechanical parameters instead of the intraoperative frozen section analysis shortens waiting times in the operating room. This study proves the general applicability of shear rheology for the determination of the mechanical properties of pancreas and the assessment of graft quality for transplantation. Porcine and human pancreas samples were examined ex vivo and a nonlinear viscoelastic behavior was observed. Pancreas was found to be more viscous than liver but both abdominal organs showed a similar flow behavior. The shear deformation dependence of healthy human pancreas was similar to porcine pancreas. An increase in the post-mortem time led to an increase in the complex modulus for a post-mortem time up to 8.5 days. Histological investigations showed that an increased amount of collagen coincides with the stiffening of the pancreatic tissue.

  5. An innovative ex-vivo porcine upper gastrointestinal model for submucosal tunnelling endoscopic resection (STER)

    PubMed Central

    Yeung, Baldwin; Chiu, Philip; Teoh, Anthony; Zheng, Linfu; Chan, Shannon; Lam, Kelvin; Tang, Raymond; Ng, Enders K. W.

    2016-01-01

    Background and study aims: Submucosal tunnelling endoscopic resection (STER) is a novel endoscopic technique to remove submucosal tumour (SMT). We propose a novel, low cost simulator for training of techniques for STER. Patients and methods: The model consisted of an ex-planted porcine oesophagus, stomach and duodenum with marbles embedded surgically in the submucosal plane. Two expert endoscopists with experience in submucosal tunnelling and 5 board-certified endoscopists with no experience in submucosal tunnelling were recruited. Participants were asked to perform a diagnostic endoscopy and 2 STER procedures, 1 in the oesophagus and 1 in the stomach. They also answered a structured questionnaire. Factors including operative time, mucosal and muscular injury rate, injection volume and accuracy of endoscopic closure were assessed. Results: The median time for localization of all SMTs was 40.1 seconds for experts and 38.5 seconds for novices (P = 1.000). For esophageal STER, the length of mucosal incisions and tunnelling distances were comparable between the 2 groups. The median volume injected by the novice group was significantly lower than the experts (15 mL vs 42.5 mL (P = 0.05). The median tunnelling time per length was 25.9 seconds/mm for the experts and 40.8 seconds/mm for the novice group (P = 0.38). There was a higher rate of mucosal injury and muscular perforation in the novice group (8 vs 0; P = 0.05). For gastric STER, the length of mucosal incisions and tunnel distances were comparable between the 2 groups. The median tunnelling time per length for the experts was 23.3 seconds/mm and 34.6 seconds/mm for the novice group (P = 0.38). One mucosal injury was incurred by a novice. The rate of dissection in the stomach and the oesophagus was not statistically different (P = 0.620). All participants voted that the model provides a realistic simulation and recommended it for training. Conclusions: STER is an advanced endoscopic

  6. Protective effect of active perfusion in porcine models of acute myocardial ischemia.

    PubMed

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-10-01

    Mortality rates associated with off‑pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor‑α (TNF‑α), cardiac troponin (cTnI), creatine kinase‑myocardial band (CK‑MB), interleukin (IL)‑6, IL‑10, B‑cell lymphoma 2 (Bcl‑2), and caspase‑3 were detected using enzyme‑linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, an increased rate of myocardial apoptosis, and a decreased expression level of anti‑apoptotic protein, Bcl‑2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl‑2. Furthermore, the current study indicated that active perfusion was more efficacious

  7. Protective effect of active perfusion in porcine models of acute myocardial ischemia

    PubMed Central

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-01-01

    Mortality rates associated with off-pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor-α (TNF-α), cardiac troponin (cTnI), creatine kinase-myocardial band (CK-MB), interleukin (IL)-6, IL-10, B-cell lymphoma 2 (Bcl-2), and caspase-3 were detected using enzyme-linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, an increased rate of myocardial apoptosis, and a decreased expression level of anti-apoptotic protein, Bcl-2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl-2. Furthermore, the current study indicated that active perfusion was more efficacious in maintaining myocardial perfusion and alleviating

  8. Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

    PubMed Central

    Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

    2013-01-01

    Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

  9. The updated experimental proteinoid model

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Nakashima, T.; Przybylski, A.; Syren, R. M.

    1982-01-01

    The experimental proteinoid model includes new results indicating that polymers sufficiently rich in basic amino acid catalyze the synthesis of peptides from ATP and amino acids and of oligonucleotides from ATP. The need for simulation syntheses of amino acids yielding significant proportions of basic amino acids is now in focus. The modeled simultaneous protocellular synthesis of peptides and polynucleotides is part of a more comprehensive proposal for the origin of the coded genetic mechanism. The finding of membrane and action potentials in proteinoid microspheres, with or without added lecithin, is reported. The crucial nature of a nonrandom matrix for protocells is developed.

  10. Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model

    PubMed Central

    Sutton, Jonathan T.; Ivancevich, Nikolas M.; Perrin, Stephen R.; Vela, Deborah C.; Holland, Christy K.

    2013-01-01

    Using an FDA-approved contrast agent (Definity®) and thrombolytic drug (rt-PA), we investigated ultrasound-enhanced thrombolysis in two whole-blood clot models. Porcine venous blood was collected from donor hogs and coagulated in two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombolysis model, while an intermittent ultrasound scheme previously developed to maximize stable cavitation was applied and acoustic emissions were detected. Exposure of clots to 3.15 μg/mL rt-PA promoted lysis in both clot models, compared to exposure to plasma alone. However, in the presence of rt-PA, Definity®, and ultrasound, only unretracted clots experienced significant enhancement of thrombolysis compared to treatment with rt-PA. In these clots, microscopy studies revealed loose erythrocyte aggregates, a significantly less extensive fibrin network, and a higher porosity, which may facilitate increase penetration of thrombolytics by cavitation. PMID:23453629

  11. Biodegradable lysine-derived polyurethane scaffolds promote healing in a porcine full-thickness excisional wound model

    PubMed Central

    Adolph, Elizabeth J.; Pollins, Alonda C.; Cardwell, Nancy L.; Davidson, Jeffrey M.; Guelcher, Scott A.; Nanney, Lillian B.

    2014-01-01

    Lysine-derived polyurethane scaffolds (LTI-PUR) support cutaneous wound healing in loose-skinned small animal models. Due to the physiological and anatomical similarities of human and pig skin we investigated the capacity of LTI-PUR scaffolds to support wound healing in a porcine excisional wound model. Modifications to scaffold design included the addition of carboxymethylcellulose (CMC) as a porogen to increase interconnectivity and an additional plasma treatment (Plasma) to decrease surface hydrophobicity. All LTI-PUR scaffold and formulations supported cellular infiltration and were biodegradable. At 15 days, CMC and Plasma scaffolds simulated increased macrophages more so than LTI PUR or no treatment. This response was consistent with macrophage-mediated oxidative degradation of the lysine component of the scaffolds. Cell proliferation was similar in control and scaffold treated wounds at 8 and 15 days. Neither apoptosis nor blood vessel area density showed significant differences in the presence of any of the scaffold variations compared to untreated wounds, providing further evidence that these synthetic biomaterials had no adverse effects on those pivotal wound healing processes. During the critical phase of granulation tissue formation in full thickness porcine excisional wounds, LTI-PUR scaffolds supported tissue infiltration, while undergoing biodegradation. Modifications to scaffold fabrication modify the reparative process. This study emphasizes the biocompatibility and favorable cellular responses of PUR scaffolding formulations in a clinically relevant animal model. PMID:25290884

  12. EXPERIMENTAL MODELLING OF AORTIC ANEURYSMS

    PubMed Central

    Doyle, Barry J; Corbett, Timothy J; Cloonan, Aidan J; O’Donnell, Michael R; Walsh, Michael T; Vorp, David A; McGloughlin, Timothy M

    2009-01-01

    A range of silicone rubbers were created based on existing commercially available materials. These silicones were designed to be visually different from one another and have distinct material properties, in particular, ultimate tensile strengths and tear strengths. In total, eleven silicone rubbers were manufactured, with the materials designed to have a range of increasing tensile strengths from approximately 2-4MPa, and increasing tear strengths from approximately 0.45-0.7N/mm. The variations in silicones were detected using a standard colour analysis technique. Calibration curves were then created relating colour intensity to individual material properties. All eleven materials were characterised and a 1st order Ogden strain energy function applied. Material coefficients were determined and examined for effectiveness. Six idealised abdominal aortic aneurysm models were also created using the two base materials of the study, with a further model created using a new mixing technique to create a rubber model with randomly assigned material properties. These models were then examined using videoextensometry and compared to numerical results. Colour analysis revealed a statistically significant linear relationship (p<0.0009) with both tensile strength and tear strength, allowing material strength to be determined using a non-destructive experimental technique. The effectiveness of this technique was assessed by comparing predicted material properties to experimentally measured methods, with good agreement in the results. Videoextensometry and numerical modelling revealed minor percentage differences, with all results achieving significance (p<0.0009). This study has successfully designed and developed a range of silicone rubbers that have unique colour intensities and material strengths. Strengths can be readily determined using a non-destructive analysis technique with proven effectiveness. These silicones may further aid towards an improved understanding of the

  13. Porcine Head Response to Blast

    PubMed Central

    Shridharani, Jay K.; Wood, Garrett W.; Panzer, Matthew B.; Capehart, Bruce P.; Nyein, Michelle K.; Radovitzky, Raul A.; Bass, Cameron R. ‘Dale’

    2012-01-01

    Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300–2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G’s and were well correlated with peak incident overpressure (R2 = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are

  14. Esophageal dilation with integrated balloon imaging: initial evaluation in a porcine model

    PubMed Central

    Siersema, Peter D.

    2013-01-01

    Background: When treating achalasia, balloon dilation is often combined with fluoroscopy to allow the lower esophageal sphincter to be visualized as it is being dilated. We sought to evaluate a new balloon dilation technology, EsoFLIP, which allows the shape of the balloon to be visualized in a nonradiographic manner by using impedance planimetry electrodes located within the dilation balloon. Methods: Two pigs weighing 35 kg were used. The EsoFLIP balloon dilator was introduced under endoscopic visualization. Successive injections of 50, 60, 70 and 85 mL into the dilation balloon permitted dilations at increasing diameters to be achieved. Following each dilation fluid was withdrawn to leave 30 mL in the balloon and an EsoFLIP image was captured to track progressive dilation of the gastroesophageal junction (GEJ). Results: The EsoFLIP catheter was safely deployed in the two pigs and no complications were noted. For pig 1, during dilation, the measured balloon diameter at the waist was 24.1, 28.9, 29.2 and 30.0 mm for balloon dilation volumes of 50, 60, 70 and 85 mL respectively. For pig 2 the corresponding diameter at the waist was 22.8, 27.1, 28.5 and 29.4 mm. The GEJ diameter increased from 12.5 and 12.4 mm to 17.4 and 17.5mm for pigs 1 and 2 respectively. Distensibility of the GEJ in pig 1 increased from 2.3 mm2/mmHg before to 4.4 mm2/mmHg after dilation and in pig 2 from 4.4 to 9.6 mm2/mmHg. The GEJ substantively achieved its final diameter after the dilation using just 50 mL in the balloon. Conclusions: We demonstrated technical feasibility and safety of the EsoFLIP dilator in a porcine model. Further studies in humans with achalasia remain to be conducted, which, besides demonstrating technical feasibility, should also evaluate the use of distensibility measurements taken during dilation to predict outcomes. PMID:23503681

  15. Extracorporeal Life Support during Cardiac Arrest Resuscitation in a Porcine Model of Ventricular Fibrillation

    PubMed Central

    Reynolds, Joshua C.; Salcido, David D.; Sundermann, Matthew L.; Koller, Allison C.; Menegazzi, James J.

    2013-01-01

    Abstract: Implementation barriers for extracorporeal life support in out-of-hospital cardiac arrest (OHCA) include initiation delay and candidate selection. We explored ischemia duration, cardiopulmonary resuscitation (CPR) duration, and physiologic variables that discriminated animals with return of spontaneous circulation (ROSC). We instrumented eight female swine (31.9 ± 9.8 kg) with femoral artery and external jugular vein cannula. After 8 (n = 4) or 15 (n = 4) minutes ventricular fibrillation (VF), animals received 30, 40, 50, or 60 minutes of CPR and then drugs (.6 U/kg vasopressin, .1 mg/kg epinephrine, .1 mg/kg propranolol, sodium bicarbonate as indicated) after 5 minutes of CPR. Extracorporeal membrane oxygenation (ECMO) flow rate was 3 L/min ≤2 hours and then 1.5 L/min ≤2 hours before weaning. Animals were defibrillated (150 J biphasic) ≥15 minutes ECMO. Primary outcome for successful resuscitation was ROSC (organized rhythm with systolic blood pressure >80 mmHg). We measured arterial blood gas, electrolytes, mean arterial pressure (MAP), coronary perfusion pressure (CPP), and five quantitative VF waveform measures at key intervals. Continuous variables were compared with two-sample t test. All 8-minute VF animals were successfully resuscitated and had ROSC. MAP was higher at the beginning (27.0 ± 7.1 vs. 15.0 ± 4.4; p = .03) and end (31.3 ± 12.8 vs. 11.5 ± 7.3; p = .03) of CPR in animals successfully resuscitated. CPP was higher at the beginning of CPR (11.9 ± 4.6 vs. 3.3 ± 2.2; p = .01) and the end of CPR (18.5 ± 12.1 vs. .9 ± 1.4; p = .03) among animals with ROSC. Amplitude spectrum area (AMSA) was superior at the end of CPR (–2.0 ± 1.8 vs. –5.0 ± 1.4; p = .04) in animals successfully resuscitated. In a porcine OHCA model, MAP and CPP at the beginning and end of CPR were higher in animals successfully resuscitated. AMSA was superior at the end of CPR in animals successfully resuscitated. PMID:23691782

  16. Comparison of Two Gelatin and Thrombin Combination Hemostats in a Porcine Liver Abrasion Model

    PubMed Central

    Atlee, Holly D.; Mannone, Angela J.; Dwyer, Joseph; Lin, Lawrence; Goppelt, Andreas; Redl, Heinz

    2013-01-01

    Background: Surgical hemostasis is achieved using adjunctive hemostats when conventional methods fail. Objective: This study compares the effectiveness of two adjunctive gelatin-thrombin hemostats. Hypothesis: To determine effectiveness, hemostats were compared in vivo, in vitro, and using scanning electron microscopy (SEM). Methods: In vivo, a heparinized porcine liver abrasion model was used to compare hemostatic success, degree of bleeding, and blood loss at 2, 5, and 10 minutes post-treatment. In vitro, thrombin in the supernatant of each hemostat and Red Blood Cells (RBC'S) in the supernatant of clots formed by each was compared. Results: Ultrastructure of one gelatin was smooth and the other stellate. In vivo, smooth gelatin provided superior hemostatic success at 5 (85% vs. 60%; OR: 5.3; 95% CI: 1.66 to 17.9) and 10 mins (72.5% vs. 47.5%; OR: 5.0; 95% CI: 1.55 to 16.1). Smooth gelatin had a statistically different degree of bleeding at 5 (0.58 ± 0.87 [Mean ± SD] vs. 1.03 ± 1.12; OR: 3.36; 95% CI: 1.34 to 8.41) and 10 mins (1.13 ± 1.14 vs. 1.65 ± 1.05; OR: 3.87; 95% CI: 1.62 to 9.21). Mean blood loss was less with smooth gelatin at 2 (0.07 ± 0.19 vs. 0.13 ± 0.63 ml/min), 5 (0.04 ± 0.13 vs. 0.23 ± 0.45 ml/min), and 10 mins (0.09 ± 0.24 vs. 0.21 ± 0.32 ml/min). In vitro, supernatant of smooth gelatin had significantly less thrombin (6.81 vs. 10.9 IU/ml, p = .001), and significantly less RBC's than stellate gelatin (0.07 vs. 0.09 × 106/ul, p = .0085). Conclusion: Smooth gelatin has an increased ability to retain thrombin and RBC's in vitro which may explain why it provides superior hemostatic effectiveness, superior control of bleeding, and greater reduced blood loss in vivo. PMID:23514063

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

    PubMed

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

    2016-04-29

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

  18. Evaluation of a minimally invasive renal cooling device using heat transfer analysis and an in vivo porcine model.

    PubMed

    Cervantes, Thomas M; Summers, Edward K; Batzer, Rachel; Simpson, Christie; Lewis, Raymond; Dhanani, Nadeem N; Slocum, Alexander H

    2013-06-01

    Partial nephrectomy is the gold standard treatment for renal cell carcinoma. This procedure requires temporary occlusion of the renal artery, which can cause irreversible damage due to warm ischemia after 30 min. Open surgical procedures use crushed ice to induce a mild hypothermia of 20°C in the kidney, which can increase allowable ischemia time up to 2.5 h. The Kidney Cooler device was developed previously by the authors to achieve renal cooling using a minimally invasive approach. In the present study an analytical model of kidney cooling in situ was developed using heat transfer equations to determine the effect of kidney thickness on cooling time. In vivo porcine testing was conducted to evaluate the cooling performance of this device and to identify opportunities for improved surgical handling. Renal temperature was measured continuously at 6 points using probes placed orthogonally to each other within the kidney. Results showed that the device can cool the core of the kidney to 20°C in 10-20 min. Design enhancements were made based on surgeon feedback; it was determined that the addition of an insulating air layer below the device increased difficulty of positioning the device around the kidney and did not significantly enhance cooling performance. The Kidney Cooler has been shown to effectively induce mild renal hypothermia of 20°C in an in vivo porcine model.

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

    PubMed Central

    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

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

    PubMed

    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

  1. Experimental models of hepatocellular carcinoma☆

    PubMed Central

    Newell, Philippa; Villanueva, Augusto; Friedman, Scott L.; Koike, Kazuhiko; Llovet, Josep M.

    2010-01-01

    Hepatocellular carcinoma (HCC) is a common and deadly cancer whose pathogenesis is incompletely understood. Comparative genomic studies from human HCC samples have classified HCCs into different molecular subgroups; yet, the unifying feature of this tumor is its propensity to arise upon a background of inflammation and fibrosis. This review seeks to analyze the available experimental models in HCC research and to correlate data from human populations with them in order to consolidate our efforts to date, as it is increasingly clear that different models will be required to mimic different subclasses of the neoplasm. These models will be instrumental in the evaluation of compounds targeting specific molecular pathways in future preclinical studies. PMID:18314222

  2. Epithelial Ovarian Cancer Experimental Models

    PubMed Central

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

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

    NASA Astrophysics Data System (ADS)

    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

  4. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    NASA Astrophysics Data System (ADS)

    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.

  5. Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein in Piglets.

    PubMed

    Zhu, Shanshan; Zhang, Chunyan; Wang, Jing; Wei, Li; Quan, Rong; Yang, Jiayu; Yan, Xu; Li, Zixuan; She, Ruiping; Hu, Fengjiao; Liu, Jue

    2016-01-01

    In a recent study, we reported that a recombinant protein from fusion expression of flagellin to porcine circovirus type 2 (PCV2) Cap induced robust humoral and cell-mediated immunity that afforded full protection for PCV2 infection using BALB/c mice. Here, we further evaluated the immunogenicity and protection of the recombinant protein using specific pathogen free (SPF) pigs. Twenty-five 3-week-old piglets without passively acquired immunity were divided into 5 groups. All piglets except negative controls were challenged with a virulent PCV2 at 21 days after booster vaccination and necropsied at 21 days post-challenge. Vaccination of piglets with the recombinant protein without adjuvant induced strong humoral and cellular immune responses as observed by high levels of PCV2-specific IgG antibodies and neutralizing antibodies, as well as frequencies of PCV2-specific IFN-γ-secreting cells that conferred good protection against PCV2 challenge, with significant reduced PCV2 viremia, mild lesions, low PCV2 antigen-positive cells, as well as improved body weight gain, comparable to piglets vaccinated with a commercial PCV2 subunit vaccine. These results further demonstrated that the recombinant flagellin-Cap fusion protein is capable of inducing solid protective humoral and cellular immunity when administered to pigs, thereby becoming an effective PCV2 vaccine candidate for control of PCV2 infection. PMID:26848967

  6. A New Porcine Sponge Material for Temporary Embolization: An Experimental Short-Term Pilot Study in Swine

    SciTech Connect

    Louail, B.; Sapoval, M. Bonneau, M.; Wasseff, M.; Senechal, Q.; Gaux, J-C.

    2006-10-15

    Purpose. To evaluate the safety and efficacy of a porcine-derived gelfoam, Curaspon, for the temporary occlusion of the visceral arteries. Methods. Curaspon was used for the selective embolization of segmentary hepatic, unilateral polar renal, and single lumbar arteries of 10 pigs under general anesthesia. Sequential angiographic checks were carried out and the pigs killed between 3 days and 2 weeks later. Macroscopic and microscopic studies using standard techniques were used to evaluate the immediate efficacy of embolization, duration of and completeness of recanalization on angiography, macroscopic appearance of target-organ ischemia, and microscopic analysis of inflammatory reaction. Results. Immediate arterial occlusion was obtained in all cases. Renal arteries showed a total recanalization in 63% of cases on day 7 and 100% on day 14. Total hepatic recanalization was obtained in 100% of animals on day 7. All lumbar arteries were recanalized on day 14. Microscopic analysis in the kidney revealed a mild inflammatory reaction and a progressive lysis of the Curaspon (87% of samples at day 3 showed a persistence of Curaspon and 5% at day 14). In some cases, localized and partial destruction of the arterial wall was visualized. In the liver the same patterns were observed but resolved more completely and more rapidly. Conclusions. Curaspon is an efficient material for the temporary occlusion of visceral and parietal arteries in pigs. However, arterial aneurysms were observed and a relationship of these with the material cannot be excluded.

  7. Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin-Porcine Circovirus Type 2 Cap Fusion Protein in Piglets

    PubMed Central

    Wang, Jing; Wei, Li; Quan, Rong; Yang, Jiayu; Yan, Xu; Li, Zixuan; She, Ruiping; Hu, Fengjiao; Liu, Jue

    2016-01-01

    In a recent study, we reported that a recombinant protein from fusion expression of flagellin to porcine circovirus type 2 (PCV2) Cap induced robust humoral and cell-mediated immunity that afforded full protection for PCV2 infection using BALB/c mice. Here, we further evaluated the immunogenicity and protection of the recombinant protein using specific pathogen free (SPF) pigs. Twenty-five 3-week-old piglets without passively acquired immunity were divided into 5 groups. All piglets except negative controls were challenged with a virulent PCV2 at 21 days after booster vaccination and necropsied at 21 days post-challenge. Vaccination of piglets with the recombinant protein without adjuvant induced strong humoral and cellular immune responses as observed by high levels of PCV2-specific IgG antibodies and neutralizing antibodies, as well as frequencies of PCV2-specific IFN-γ-secreting cells that conferred good protection against PCV2 challenge, with significant reduced PCV2 viremia, mild lesions, low PCV2 antigen-positive cells, as well as improved body weight gain, comparable to piglets vaccinated with a commercial PCV2 subunit vaccine. These results further demonstrated that the recombinant flagellin-Cap fusion protein is capable of inducing solid protective humoral and cellular immunity when administered to pigs, thereby becoming an effective PCV2 vaccine candidate for control of PCV2 infection. PMID:26848967

  8. Evaluation of a novel laparoscopic camera for characterization of renal ischemia in a porcine model using digital light processing (DLP) hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Olweny, Ephrem O.; Tan, Yung K.; Faddegon, Stephen; Jackson, Neil; Wehner, Eleanor F.; Best, Sara L.; Park, Samuel K.; Thapa, Abhas; Cadeddu, Jeffrey A.; Zuzak, Karel J.

    2012-03-01

    Digital light processing hyperspectral imaging (DLP® HSI) was adapted for use during laparoscopic surgery by coupling a conventional laparoscopic light guide with a DLP-based Agile Light source (OL 490, Optronic Laboratories, Orlando, FL), incorporating a 0° laparoscope, and a customized digital CCD camera (DVC, Austin, TX). The system was used to characterize renal ischemia in a porcine model.

  9. Experimental models of liver fibrosis

    PubMed Central

    Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2015-01-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  10. Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood

    PubMed Central

    Waldman, Joshua P.; Vogel, Thomas; Burlak, Christopher; Coussios, Constantin; Dominguez, Javier; Friend, Peter; Rees, Michael A.

    2013-01-01

    Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of “liver dialysis”. During a 72-hour extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-hours in the presence of an anti-porcine sialoadhesin antibody or isotype control. The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72 hour period. Sustained liver function was demonstrated throughout the perfusion. This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model. PMID:23822217

  11. Effects of an Inactivated Porcine Circovirus Type 2 (PCV2) Vaccine on PCV2 Virus Shedding in Semen from Experimentally Infected Boars ▿

    PubMed Central

    Seo, Hwi Won; Han, Kiwon; Kim, Duyeol; Oh, Yeonsu; Kang, Ikjae; Park, Changhoon; Jang, Hyun; Chae, Chanhee

    2011-01-01

    The objective of the present study was to determine the effect of an inactivated porcine circovirus type 2 (PCV2) vaccine on PCV2b virus shedding in the semen of experimentally infected boars by measuring the immunological response and the PCV2b DNA load in blood and semen. Twelve boars were randomly divided into three groups. The boars in group 1 (n = 4) were immunized with an inactivated PCV2 vaccine and were challenged with PCV2b. The boars in group 2 (n = 4) were only challenged with PCV2b. The boars in group 3 (n = 4) served as negative controls. The number of PCV2 genome copies of PCV2 in the serum and semen were significantly lower in vaccinated challenged boars than in nonvaccinated challenged boars at 7, 10, 14, 21, 32, 35, 42, 49, and 60 days postinoculation. The number of PCV2b genomes in the semen correlated with the number of PCV2b genomes in the blood in both vaccinated challenged (R = 0.714) and nonvaccinated challenged (R = 0.861) boars. The results of the present study demonstrate that the inactivated PCV2 vaccine significantly decreases the amount of PCV2b DNA shedding in semen from vaccinated boars after experimental infection with PCV2b. PMID:21613465

  12. Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus.

    PubMed

    Bulc, Michał; Gonkowski, Sławomir; Całka, Jarosław

    2015-11-01

    In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.

  13. Safety of Porcine Reproductive and Respiratory Syndrome Modified Live Virus (MLV) vaccine strains in a young pig infection model

    PubMed Central

    2013-01-01

    The objective of this study was to compare the safety of all modified live virus vaccines commercially available in Europe against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) under the same experimental conditions. For this purpose, one hundred and twenty three-week-old piglets, divided into five groups, were used. On day 0 of the experiment, nine pigs per group were removed and the remaining fifteen were vaccinated with the commercial vaccines Ingelvac PRRS MLV, Amervac PRRS, Pyrsvac-183 and Porcilis PRRS by the IM route or were mock vaccinated and used as controls. On day 3, the nine unvaccinated pigs were re-introduced into their respective groups and served as sentinel pigs. Clinical signs were recorded daily and lung lesions were determined on days 7, 14 and 21, when 5 vaccinated pigs per group were euthanized. Blood samples and swabs were taken every three days and different organs were collected at necropsy to determine the presence of PRRSV. None of the vaccines studied caused detectable clinical signs in vaccinated pigs although lung lesions were found. Altogether, these results indicate that all vaccines can be considered clinically safe. However, some differences were found in virological parameters. Thus, neither Pyrsvac-183 nor Porcilis PRRS could be detected in porcine alveolar macrophage (PAM) cultures or in lung sections used to determine PRRSV by immunohistochemistry, indicating that these viruses might have lost their ability to replicate in PAM. This inability to replicate in PAM might be related to the lower transmission rate and the delay in the onset of viremia observed in these groups PMID:24308693

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

    PubMed Central

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

    2016-01-01

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

  15. Experimental Model of Proximal Junctional Fracture after Multilevel Posterior Spinal Instrumentation

    PubMed Central

    Levasseur, Annie; Parent, Stefan; Petit, Yvan

    2016-01-01

    There is a high risk of proximal junctional fractures (PJF) with multilevel spinal instrumentation, especially in the osteoporotic spine. This problem is associated with significant morbidity and possibly the need for reoperation. Various techniques have been proposed in an attempt to decrease the risk of PJF but there is no experimental model described for in vitro production of PJF after multilevel instrumentation. The objective of this study is to develop an experimental model of PJF after multilevel posterior instrumentation. Initially, four porcine specimens including 4 vertebrae and instrumented at the 3 caudal vertebrae using a pedicle screw construct were subjected to different loading conditions. Loading conditions on porcine specimens involving cyclic loading along the axis of the center vertebral body line, with constrained flexion between 0° and 15° proximally, and fully constraining the specimen distally resulted in a fracture pattern most representative of a PJF seen clinically in humans, so to undergo human cadaveric testing with similar loading conditions was decided. Clinically relevant PJF were produced in all 3 human specimens. The experimental model described in this study will allow the evaluation of different parameters influencing the incidence and prevention of PJF after multilevel posterior spinal instrumentation. PMID:27610381

  16. Experimental Model of Proximal Junctional Fracture after Multilevel Posterior Spinal Instrumentation.

    PubMed

    Mac-Thiong, Jean-Marc; Levasseur, Annie; Parent, Stefan; Petit, Yvan

    2016-01-01

    There is a high risk of proximal junctional fractures (PJF) with multilevel spinal instrumentation, especially in the osteoporotic spine. This problem is associated with significant morbidity and possibly the need for reoperation. Various techniques have been proposed in an attempt to decrease the risk of PJF but there is no experimental model described for in vitro production of PJF after multilevel instrumentation. The objective of this study is to develop an experimental model of PJF after multilevel posterior instrumentation. Initially, four porcine specimens including 4 vertebrae and instrumented at the 3 caudal vertebrae using a pedicle screw construct were subjected to different loading conditions. Loading conditions on porcine specimens involving cyclic loading along the axis of the center vertebral body line, with constrained flexion between 0° and 15° proximally, and fully constraining the specimen distally resulted in a fracture pattern most representative of a PJF seen clinically in humans, so to undergo human cadaveric testing with similar loading conditions was decided. Clinically relevant PJF were produced in all 3 human specimens. The experimental model described in this study will allow the evaluation of different parameters influencing the incidence and prevention of PJF after multilevel posterior spinal instrumentation. PMID:27610381

  17. Experimental Model of Proximal Junctional Fracture after Multilevel Posterior Spinal Instrumentation

    PubMed Central

    Levasseur, Annie; Parent, Stefan; Petit, Yvan

    2016-01-01

    There is a high risk of proximal junctional fractures (PJF) with multilevel spinal instrumentation, especially in the osteoporotic spine. This problem is associated with significant morbidity and possibly the need for reoperation. Various techniques have been proposed in an attempt to decrease the risk of PJF but there is no experimental model described for in vitro production of PJF after multilevel instrumentation. The objective of this study is to develop an experimental model of PJF after multilevel posterior instrumentation. Initially, four porcine specimens including 4 vertebrae and instrumented at the 3 caudal vertebrae using a pedicle screw construct were subjected to different loading conditions. Loading conditions on porcine specimens involving cyclic loading along the axis of the center vertebral body line, with constrained flexion between 0° and 15° proximally, and fully constraining the specimen distally resulted in a fracture pattern most representative of a PJF seen clinically in humans, so to undergo human cadaveric testing with similar loading conditions was decided. Clinically relevant PJF were produced in all 3 human specimens. The experimental model described in this study will allow the evaluation of different parameters influencing the incidence and prevention of PJF after multilevel posterior spinal instrumentation.

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

    PubMed Central

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

    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 = 0.011 < 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. PMID:17659696

  19. Decolonisation of MRSA, S. aureus and E. coli by Cold-Atmospheric Plasma Using a Porcine Skin Model In Vitro

    PubMed Central

    Maisch, Tim; Shimizu, Tetsuji; Li, Yang-Fang; Heinlin, Julia; Karrer, Sigrid; Morfill, Gregor; Zimmermann, Julia L.

    2012-01-01

    In the last twenty years new antibacterial agents approved by the U.S. FDA decreased whereas in parallel the resistance situation of multi-resistant bacteria increased. Thus, community and nosocomial acquired infections of resistant bacteria led to a decrease in the efficacy of standard therapy, prolonging treatment time and increasing healthcare costs. Therefore, the aim of this work was to demonstrate the applicability of cold atmospheric plasma for decolonisation of Gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Methicillin-sensitive Staphylococcus aureus) and Gram-negative bacteria (E. coli) using an ex vivo pig skin model. Freshly excised skin samples were taken from six month old female pigs (breed: Pietrain). After application of pure bacteria on the surface of the explants these were treated with cold atmospheric plasma for up to 15 min. Two different plasma devices were evaluated. A decolonisation efficacy of 3 log10 steps was achieved already after 6 min of plasma treatment. Longer plasma treatment times achieved a killing rate of 5 log10 steps independently from the applied bacteria strains. Histological evaluations of untreated and treated skin areas upon cold atmospheric plasma treatment within 24 h showed no morphological changes as well as no significant degree of necrosis or apoptosis determined by the TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates for the first time that cold atmospheric plasma is able to very efficiently kill bacteria applied to an intact skin surface using an ex vivo porcine skin model. The results emphasize the potential of cold atmospheric plasma as a new possible treatment option for decolonisation of human skin from bacteria in patients in the future without harming the surrounding tissue. PMID:22558091

  20. Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Bartos, Jason A.; Matsuura, Timothy R.; Tsangaris, Adamantios; Olson, Matthew; McKnite, Scott H.; Rees, Jennifer N.; Haman, Karen; Shekar, Kadambari Chandra; Riess, Matthias L.; Bates, Frank S.; Metzger, Joseph M.; Yannopoulos, Demetris

    2016-01-01

    BACKGROUND Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. OBJECTIVES This study compared intracoronary infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST segment elevation myocardial infarction (STEMI). Cellular and mitochondrial injury were assessed. METHODS STEMI was induced in 55 pigs using 45 minutes of endovascular coronary artery occlusion. Pigs were then randomized to four groups: control, immediate intracoronary (IC) P188, delayed peripheral P188, and polyethylene glycol (PEG) infusion. Heart tissue was collected after 4 hours of reperfusion. Assessment of mitochondrial function or infarct size was performed. RESULTS Mitochondrial yield improved significantly with IC P188 treatment compared to control animals (0.25% vs. 0.13%) suggesting improved mitochondrial morphology and survival. Mitochondrial respiration and calcium retention were also significantly improved with immediate IC P188 compared to controls (complex I RCI: 7.4 vs. 3.7 and calcium retention (nmol): 1152 vs. 386). This benefit was only observed with activation of complex I of the mitochondrial respiratory chain suggesting a specific impact of ischemia and reperfusion on this complex. Infarct size and serum troponin I were significantly reduced by immediate IC P188 infusion (infarct size: 13.9% vs. 41.1% and troponin I (μg/L): 19.2 vs. 77.4 μg/L). Delayed P188 and PEG infusion did not provide a significant benefit. CONCLUSIONS Intracoronary infusion of P188 immediately upon reperfusion significantly reduces cellular and mitochondrial injury after ischemia and reperfusion in this clinically relevant porcine model of STEMI. The timing and route of delivery were critical to achieve the benefit.

  1. Efficacy of platelet-rich plasma as a shielding technique after endoscopic mucosal resection in rat and porcine models

    PubMed Central

    Lorenzo-Zúñiga, Vicente; Boix, Jaume; Moreno de Vega, Vicente; Bon, Ignacio; Marín, Ingrid; Bartolí, Ramón

    2016-01-01

    Background and study aims: The aims were to assess the efficacy of endoscopic application of Platelet-rich plasma (PRP) to prevent delayed perforation and to induce mucosal healing after endoscopic resections. Patients and methods: Colonic induced lesions were performed in rats (n = 16) and pigs (n = 4). Animals were randomized to receive onto the lesions saline (control) or PRP. Animals underwent endoscopic follow-up. Thermal injury was assessed with a 1 – 4 scale: (1) mucosal necrosis; (2) submucosal necrosis; (3) muscularis propria necrosis; and (4) serosal necrosis Results: Saline treatment showed 50 % of mortality in rats (P = 0.02). Mean ulcerated area after 48 hours and 7 days was significantly smaller with PRP than with saline (0.27 ± 0.02 cm2 and 0.08 ± 0.01 cm2 vs. 0.56 ± 0.1 cm2 and 0.40 ± 0.06 cm2; P < 0.001). The incidence of thermal injury was significantly lower with PRP (1.25 ± 0.46) than in controls (2.25 ± 0.50); P = 0.006. The porcine model showed a trend toward higher mucosal restoration in animals treated with PRP than with saline at weeks 1 and 2 (Median area in cm2: 0.55 and 0.40 vs. 1.32 and 0.79) Conclusions: Application of PRP to colonic mucosal lesions showed strong healing properties in rat and porcine models. PMID:27540573

  2. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  3. Renal artery nerve distribution and density in the porcine model: biologic implications for the development of radiofrequency ablation therapies.

    PubMed

    Tellez, Armando; Rousselle, Serge; Palmieri, Taylor; Rate, William R; Wicks, Joan; Degrange, Ashley; Hyon, Chelsea M; Gongora, Carlos A; Hart, Randy; Grundy, Will; Kaluza, Greg L; Granada, Juan F

    2013-12-01

    Catheter-based renal artery denervation has demonstrated to be effective in decreasing blood pressure among patients with refractory hypertension. The anatomic distribution of renal artery nerves may influence the safety and efficacy profile of this procedure. We aimed to describe the anatomic distribution and density of periarterial renal nerves in the porcine model. Thirty arterial renal sections were included in the analysis by harvesting a tissue block containing the renal arteries and perirenal tissue from each animal. Each artery was divided into 3 segments (proximal, mid, and distal) and assessed for total number, size, and depth of the nerves according to the location. Nerve counts were greatest proximally (45.62% of the total nerves) and decreased gradually distally (mid, 24.58%; distal, 29.79%). The distribution in nerve size was similar across all 3 sections (∼40% of the nerves, 50-100 μm; ∼30%, 0-50 μm; ∼20%, 100-200 μm; and ∼10%, 200-500 μm). In the arterial segments ∼45% of the nerves were located within 2 mm from the arterial wall whereas ∼52% of all nerves were located within 2.5 mm from the arterial wall. Sympathetic efferent fibers outnumbered sensory afferent fibers overwhelmingly, intermixed within the nerve bundle. In the porcine model, renal artery nerves are seen more frequently in the proximal segment of the artery. Nerve size distribution appears to be homogeneous throughout the artery length. Nerve bundles progress closer to the arterial wall in the distal segments of the artery. This anatomic distribution may have implications for the future development of renal denervation therapies.

  4. Preliminary evidence of age-dependent clinical signs associated with porcine circovirus 2b in experimentally infected CH3/Rockefeller mice.

    PubMed

    de Castro, Alessandra M M G; Cruz, Taís F; Yamada, Katarina B; Gerber, Priscilla F; Gabardo, Michelle P; Araújo, João P; Guedes, Roberto M C; Mori, Cinthia K; Oliveira, Camila P; Santos, Sueli S; Richtzenhain, Leonardo J

    2015-12-01

    Mice and rats are susceptible to porcine circovirus 2b (PCV2) infection under field and experimental conditions. However, whether PCV2 induces disease in rodents remains a matter of debate. The objectives of the present study were to determine whether PCV2-induced disease in mice is age-dependent and whether intranasally inoculated animals are able to infect animals they come into contact with. Twenty-five CH3/Rockefeller mice were divided into six groups and intranasally inoculated with 25μL of either PCV2b or PBS on days 0, 3 and 6. One group remained untreated. Two age groups were tested: 3-week-old mice and 6-week-old mice. The administration of three PCV2 intranasal inoculations at intervals of three days was able to induce infection and support virus transmission in susceptible mice, regardless of the age at inoculation. The clinical signs associated with PCV2 infection were more severe in younger mice, and PCV2-DNA load was higher in their faeces. In conclusion, PCV2 induced disease in mice. PMID:26679798

  5. Preliminary evidence of age-dependent clinical signs associated with porcine circovirus 2b in experimentally infected CH3/Rockefeller mice.

    PubMed

    de Castro, Alessandra M M G; Cruz, Taís F; Yamada, Katarina B; Gerber, Priscilla F; Gabardo, Michelle P; Araújo, João P; Guedes, Roberto M C; Mori, Cinthia K; Oliveira, Camila P; Santos, Sueli S; Richtzenhain, Leonardo J

    2015-12-01

    Mice and rats are susceptible to porcine circovirus 2b (PCV2) infection under field and experimental conditions. However, whether PCV2 induces disease in rodents remains a matter of debate. The objectives of the present study were to determine whether PCV2-induced disease in mice is age-dependent and whether intranasally inoculated animals are able to infect animals they come into contact with. Twenty-five CH3/Rockefeller mice were divided into six groups and intranasally inoculated with 25μL of either PCV2b or PBS on days 0, 3 and 6. One group remained untreated. Two age groups were tested: 3-week-old mice and 6-week-old mice. The administration of three PCV2 intranasal inoculations at intervals of three days was able to induce infection and support virus transmission in susceptible mice, regardless of the age at inoculation. The clinical signs associated with PCV2 infection were more severe in younger mice, and PCV2-DNA load was higher in their faeces. In conclusion, PCV2 induced disease in mice.

  6. A custom tailored model to investigate skin penetration in porcine skin and its comparison with human skin.

    PubMed

    Herbig, Michael E; Houdek, Pia; Gorissen, Sascha; Zorn-Kruppa, Michaela; Wladykowski, Ewa; Volksdorf, Thomas; Grzybowski, Stephan; Kolios, Georgios; Willers, Christoph; Mallwitz, Henning; Moll, Ingrid; Brandner, Johanna M

    2015-09-01

    Reliable models for the determination of skin penetration and permeation are important for the development of new drugs and formulations. The intention of our study was to develop a skin penetration model which (1) is viable and well supplied with nutrients during the period of the experiment (2) is mimicking human skin as far as possible, but still is independent from the problems of supply and heterogeneity, (3) can give information about the penetration into different compartments of the skin and (4) considers specific inter-individual differences in skin thickness. In addition, it should be quick and inexpensive (5) and without ethical implications (6). Using a chemically divers set of four topically approved active pharmaceutical ingredients (APIs), namely diclofenac, metronidazole, tazarotene, and terbinafine, we demonstrated that the model allows reliable determination of drug concentrations in different layers of the viable epidermis and dermis. For APIs susceptible for skin metabolism, the extent of metabolic transformation in epidermis and dermis can be monitored. Furthermore, a high degree of accordance in the ability for discrimination of skin concentrations of the substances in different layers was found in models derived from porcine and human skin. Viability, proliferation, differentiation and markers for skin barrier function were surveyed in the model. This model, which we call 'Hamburg model of skin penetration' is particularly suited to support a rational ranking and selection of dermatological formulations within drug development projects.

  7. New model systems for experimental evolution.

    PubMed

    Collins, Sinéad

    2013-07-01

    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans.

  8. Electrosurgical vessel sealing tissue temperature: experimental measurement and finite element modeling.

    PubMed

    Chen, Roland K; Chastagner, Matthew W; Dodde, Robert E; Shih, Albert J

    2013-02-01

    The temporal and spatial tissue temperature profile in electrosurgical vessel sealing was experimentally measured and modeled using finite element modeling (FEM). Vessel sealing procedures are often performed near the neurovascular bundle and may cause collateral neural thermal damage. Therefore, the heat generated during electrosurgical vessel sealing is of concern among surgeons. Tissue temperature in an in vivo porcine femoral artery sealed using a bipolar electrosurgical device was studied. Three FEM techniques were incorporated to model the tissue evaporation, water loss, and fusion by manipulating the specific heat, electrical conductivity, and electrical contact resistance, respectively. These three techniques enable the FEM to accurately predict the vessel sealing tissue temperature profile. The averaged discrepancy between the experimentally measured temperature and the FEM predicted temperature at three thermistor locations is less than 7%. The maximum error is 23.9%. Effects of the three FEM techniques are also quantified.

  9. [Sutureless hepatic transection using a new radiofrequency assisted device. Theoretical model, experimental study and clinic trial].

    PubMed

    Martínez-Serrano, María Ángeles; Grande, Luis; Burdío, Fernando; Berjano, Enrique; Poves, Ignasi; Quesada, Rita

    2011-03-01

    The ideal instrument for performing hepatic transection should combine safe and rapid haemostasis in a single tool. We present a new multidisciplinary investigation designed to develop a hepatic transection device assisted by radiofrequency (RF); the investigation included: a computerised theoretical model, and experimental study and a clinical trial of this device. The theoretic modelling was performed by computer, based on the Finite Elements Method (FEM), with the objective of studying the distribution of electrical energy and temperature in the tissue, and to assess the effect of the characteristics of the instrument. The experimental study, based on an in vivo porcine model, suggested that the new instrument would allow the transection velocity of the hepatic parenchyma to be increased with lower bleeding per transection area compared with other techniques extensively used in liver surgery. These data should enable the first phase of clinical trial to be conducted, with preliminary results that suggest that the new device is safe and effective.

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

    PubMed

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

    2015-08-01

    Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P < 0.05 for all time points). Cerebral blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be

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

    SciTech Connect

    Deodhar, Ajita; Monette, Sebastien; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Solomon, Stephen B.

    2011-12-15

    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.

  12. Using heterogeneity in the population structure of U.S. swine farms to compare transmission models for porcine epidemic diarrhoea

    PubMed Central

    O’Dea, Eamon B.; Snelson, Harry; Bansal, Shweta

    2016-01-01

    In 2013, U.S. swine producers were confronted with the disruptive emergence of porcine epidemic diarrhoea (PED). Movement of animals among farms is hypothesised to have played a role in the spread of PED among farms. Via this or other mechanisms, the rate of spread may also depend on the geographic density of farms and climate. To evaluate such effects on a large scale, we analyse state-level counts of outbreaks with variables describing the distribution of farm sizes and types, aggregate flows of animals among farms, and an index of climate. Our first main finding is that it is possible for a correlation analysis to be sensitive to transmission model parameters. This finding is based on a global sensitivity analysis of correlations on simulated data that included a biased and noisy observation model based on the available PED data. Our second main finding is that flows are significantly associated with the reports of PED outbreaks. This finding is based on correlations of pairwise relationships and regression modeling of total and weekly outbreak counts. These findings illustrate how variation in population structure may be employed along with observational data to improve understanding of disease spread. PMID:26947420

  13. Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.

    PubMed

    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 response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

  14. Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms.

    PubMed

    Yang, Qingping; Phillips, Priscilla L; Sampson, Edith M; Progulske-Fox, Ann; Jin, Shouguang; Antonelli, Patrick; Schultz, Gregory S

    2013-01-01

    Bacterial biofilms have been proposed to be a major factor contributing to the failure of chronic wounds to heal because of their increased tolerance to antimicrobial agents and the prolonged inflammation they cause. Phenotypic characteristics of bacterial biofilms vary depending on the substratum to which they attach, the nutritional environment, and the microorganisms within the biofilm community. To develop an ex vivo biofilm model that more closely mimics biofilms in chronic skin wounds, we developed an optimal procedure to grow mature biofilms on a central partial-thickness wound in 12-mm porcine skin explants. Chlorine gas produced optimal sterilization of explants while preserving histological properties of the epidermis and dermis. Pseudomonas aeruginosa and Staphylococcus aureus developed mature biofilms after 3 days that had dramatically increased tolerance to gentamicin and oxacillin (∼100× and 8,000× minimal inhibitory concentration, respectively) and to sodium hypochlorite (0.6% active chlorine). Scanning electron microscopy and confocal microscopy verified extensive exopolymeric biofilm structures on the explants. Despite a significant delay, a ΔlasI quorum-sensing mutant of P. aeruginosa developed biofilm as antibiotic-tolerant as wild-type after 3 days. This ex vivo model simulates growth of biofilms on skin wounds and provides an accurate model to assess effects of antimicrobial agents on mature biofilms.

  15. Experimental model updating using frequency response functions

    NASA Astrophysics Data System (ADS)

    Hong, Yu; Liu, Xi; Dong, Xinjun; Wang, Yang; Pu, Qianhui

    2016-04-01

    In order to obtain a finite element (FE) model that can more accurately describe structural behaviors, experimental data measured from the actual structure can be used to update the FE model. The process is known as FE model updating. In this paper, a frequency response function (FRF)-based model updating approach is presented. The approach attempts to minimize the difference between analytical and experimental FRFs, while the experimental FRFs are calculated using simultaneously measured dynamic excitation and corresponding structural responses. In this study, the FRF-based model updating method is validated through laboratory experiments on a four-story shear-frame structure. To obtain the experimental FRFs, shake table tests and impact hammer tests are performed. The FRF-based model updating method is shown to successfully update the stiffness, mass and damping parameters of the four-story structure, so that the analytical and experimental FRFs match well with each other.

  16. Comparison of sow and/or piglet vaccination of 3 commercial porcine circovirus type 2 (PCV2) single-dose vaccines on pigs under experimental PCV2 challenge.

    PubMed

    Oh, Yeonsu; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee

    2014-08-27

    The objective of the present study was to compare the effect of sow and/or piglet vaccination regimen by three commercial porcine circovirus type 2 (PCV2) vaccines on pigs experimentally challenged with PCV2 at 84 days of age based on immunological, virological, and pathological evaluation. One hundred and nineteen piglets born to vaccinated or non-vaccinated sows were divided into 17 groups. A portion of the pigs with or without passively acquired immunity was vaccinated at 21 or 49 days of age. Regardless of the PCV2 vaccine, the combination of sow and pig (49 days of age) vaccinations significantly (P<0.05) reduced PCV2 viremia, induced higher log2 transformed neutralizing antibody titers, and resulted in higher proportion of CD4(+)CD8(+)IFN-γ(+) lymphocyte subsets than the sow vaccination alone, the pig (21 or 49 days of age) vaccination alone, and the combination of sow and pig (21 days of age) vaccinations at various days post challenge. The results showed a significant negative correlation between maternally derived antibodies at the day of vaccination and the increment of antibody titers to PCV2 at 28 days post vaccination in the combination of sow and pig (21 days of age) vaccinations but not the combination of sow and pig (49 days of age) vaccinations. The combination of sow and pig (49 days of age) vaccinations could be more effective for controlling PCV2 infection if PCV2 the infection occurs during the growing-finishing period in herds. Optimal vaccination strategies must balance the advantage of delayed vaccination with the need to induce immunity prior to exposure to pathogens under field conditions.

  17. In-vivo regional myocardial perfusion measurements in a porcine model by ECG-gated multislice computed tomography

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Liang, Yun; Meyer, Cristopher A.; Teague, Shawn; Stecker, Michael; Hutchins, Gary; McLennan, Gordon; Persohn, Scott

    2003-05-01

    Purpose: To evaluate whether functional multi-slice computed tomography (MSCT) can identify regional areas of normally perfused and ischemic myocardium in a porcine model. Material and Methods: Three out bred pigs, two of which had ameroids surgically implanted to constrict flow within the LAD and LCx coronary arteries, were injected with 25 mL of iopromide (Isovue) at a rate of 5 mL/second via the femoral or jugular vein. Sixty axial scans along the short axis of the heart was acquired on a 16-slice CT scanner (Philips MX8000-IDT) triggered at end-diastole of the cardiac cycle and acquiring an image within 270 msec. A second series of scans were taken after an intravenous injection of a vasodilator, 150 μg/kg/min of adenosine. ROIs were drawn around the myocardial tissue and the resulting time-density curves were used to extract perfusion values. Results: Determination of the myocardial perfusion and fractional blood volume implementing three different perfusion models. A 5-point averaging or 'smoothing' algorithm was employed to effectively filter the data due to its noisy nature. The (preliminary) average perfusion and fractional blood volume values over selected axial slices for the pig without an artificially induced stenosis were measured to be 84 +/- 22 mL/min/100g-tissue and 0.17 +/- 0.04 mL/g-tissue, the former is consistent with PET scan and EBCT results. The pig with a stenosis in the left LAD coronary artery showed a reduced global perfusion value -- 45 mL/min/100g-tissue. Correlations in regional perfusion values relative to the stenosis were weak. During the infusion of adenosine, averaged perfusion values for the three subjects increased by 46 (+/-45) percent, comparable to increases measured with PET. Conclusion: Quantifying global perfusion values using MDCT appear encouraging. Future work will focus resolving the systematic effects from noise due to signal fluctuation from the porcine tachyardia (80-93 BPM) and provide a more robust measurement

  18. Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

    PubMed Central

    Wang, Huaijun; Felt, Stephen A.; Machtaler, Steven; Guracar, Ismayil; Luong, Richard; Bettinger, Thierry; Tian, Lu; Lutz, Amelie M.

    2015-01-01

    Purpose To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin–targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard. Materials and Methods The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin–targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 108 MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis. Results Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 108 MB/kg and plateaued between a dose of 10 and a dose of 20 × 108 MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin). Conclusion Quantitative measurements of inflammation obtained by using dual-selectin–targeted US

  19. Porcine prion protein amyloid.

    PubMed

    Hammarström, Per; Nyström, Sofie

    2015-01-01

    Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions. PMID:26218890

  20. Porcine prion protein amyloid

    PubMed Central

    Hammarström, Per; Nyström, Sofie

    2015-01-01

    ABSTRACT Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions. PMID:26218890

  1. Porcine prion protein amyloid.

    PubMed

    Hammarström, Per; Nyström, Sofie

    2015-01-01

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

  2. Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

    PubMed

    Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

    2006-01-01

    Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement. PMID:16049525

  3. 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

    PubMed Central

    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

  4. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    PubMed Central

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

    2016-01-01

    Background The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. Methods The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. Results All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. Conclusion In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms. PMID:27144001

  5. Increasing the presence of biofilm and healing delay in a porcine model of MRSA-infected wounds.

    PubMed

    Roche, Eric D; Renick, Paul J; Tetens, Shannon P; Ramsay, Sarah J; Daniels, Egeenee Q; Carson, Dennis L

    2012-01-01

    Data supporting the concept that microbial biofilms are a major cause of non-healing ulcers remain limited. A porcine model was established where delayed healing resulted from methicillin-resistant Staphylococcus aureus (MRSA) infection in full-thickness wounds. At the end of one study a wound remaining open was sampled and a MRSA strain was isolated. This pig-passaged strain was used as the inoculating strain in several subsequent studies. The resulting MRSA wound infections exhibited a greater, more stable tissue bioburden than seen in studies using the parent strain. Furthermore, wounds infected with the passaged strain experienced a greater delay in healing. To understand whether these changes corresponded to an increased biofilm character of the wound infection, wound biopsy samples from studies using either the parent or passaged MRSA strains were examined microscopically. Evidence of biofilm was observed for both strains, as most samples at a minimum had multiple isolated, dense microcolonies of bacteria. However, the passaged MRSA resulted in bacterial colonies of greater frequency and size that occurred more often in concatenated fashion to generate extended sections of biofilm. These results provide a model case in which increasing biofilm character of a wound infection corresponded with a greater delay in wound healing.

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

    PubMed

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

    2008-07-27

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

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

    PubMed

    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.

  8. A detailed method for preparation of a functional and flexible blood-brain barrier model using porcine brain endothelial cells.

    PubMed

    Patabendige, Adjanie; Skinner, Robert A; Morgan, Louise; Abbott, N Joan

    2013-07-12

    The blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels and forms the critical interface regulating molecular flux between blood and brain. It contributes to homoeostasis of the microenvironment of the central nervous system and protection from pathogens and toxins. Key features of the BBB phenotype are presence of complex intercellular tight junctions giving a high transendothelial electrical resistance (TEER), and strongly polarised (apical:basal) localisation of transporters and receptors. In vitro BBB models have been developed from primary culture of brain endothelial cells of several mammalian species, but most require exposure to astrocytic factors to maintain the BBB phenotype. Other limitations include complicated procedures for isolation, poor yield and batch-to-batch variability. Some immortalised brain endothelial cell models have proved useful for transport studies but most lack certain BBB features and have low TEER. We have developed an in vitro BBB model using primary cultured porcine brain endothelial cells (PBECs) which is relatively simple to prepare, robust, and reliably gives high TEER (mean~800 Ω cm(2)); it also shows good functional expression of key tight junction proteins, transporters, receptors and enzymes. The model can be used either in monoculture, for studies of molecular flux including permeability screening, or in co-culture with astrocytes when certain specialised features (e.g. receptor-mediated transcytosis) need to be maximally expressed. It is also suitable for a range of studies of cell:cell interaction in normal physiology and in pathology. The method for isolating and growing the PBECs is given in detail to facilitate adoption of the model. This article is part of a Special Issue entitled Companion Paper. PMID:23603406

  9. Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model

    PubMed Central

    Guzman-Bautista, Edgar R; Garcia-Ruiz, Carlos E; Gama-Espinosa, Alicia L; Ramirez-Estudillo, Carmen; Rojas-Gomez, Oscar I; Vega-Lopez, Marco A

    2014-01-01

    Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA)-specific MatAb on the anti-OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti-OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination. PMID:24754050

  10. Synthesis and anti-staphylococcal activity of TiO2 nanoparticles and nanowires in ex vivo porcine skin model.

    PubMed

    Nataraj, Namrata; Anjusree, G S; Madhavan, Asha Anish; Priyanka, P; Sankar, Deepthi; Nisha, N; Lakshmi, S V; Jayakumar, R; Balakrishnan, Avinash; Biswas, Raja

    2014-05-01

    Staphylococcus aureus is one of the major causes of skin and soft tissue infections. In this study we compared the antimicrobial activity of two different TiO2 nanoformulations against Staphylococcus aureus. We synthesized TiO2 nanoparticles of approximately 80 nm diameter and TiO2 nanowires of approximately 100 nm diameter. Both nanoformulations possess anti-microbial activity; were non-hemolytic and cytocompatible. However, the anti-staphylococcal activity of TiO2 nanowires was better than the nanoparticles. In broth culture, growth of S. aureus was only partially inhibited by 2% and 4 wt% TiO2 nanoparticles and completely inhibited by TiO2 nanowires till 24 h. TiO2 nanowires treated S. aureus cells exhibits diminished membrane potential than nanoparticle treated cells. The anti-microbial properties of both TiO2 nanoformulations were validated using ex vivo porcine skin model which supplements the in vitro assays. Anti-bacterial activity of the TiO2 nanowires were also validated against multi drug resistant pathogenic strains of S. aureus, showing the clinical potency of the TiO2 nanowires compared to its nanoparticles.

  11. A porcine model of early atrial fibrillation using a custom-built, radio transmission-controlled pacemaker.

    PubMed

    Schwarzl, Michael; Alogna, Alessio; Zweiker, David; Verderber, Jochen; Huber, Stefan; Manninger, Martin; Scherr, Daniel; Antoons, Gudrun; Pieske, Burkert M; Post, Heiner; Lueger, Andreas

    2016-01-01

    Mechanisms underlying atrial remodeling toward atrial fibrillation (AF) are incompletely understood. We induced AF in 16 pigs by 6weeks of rapid atrial pacing (RAP, 600bpm) using a custom-built, telemetrically controlled pacemaker. AF evolution was monitored three times per week telemetrically in unstressed, conscious animals. We established a dose-response relationship between RAP duration and occurrence of sustained AF >60minutes. Left atrial (LA) dilatation was present already at 2weeks of RAP. There was no evidence of left ventricular heart failure after 6weeks of RAP. As a proof-of-principle, arterial hypertension was induced in 5/16 animals by implanting desoxycorticosterone acetate (DOCA, an aldosterone-analog) subcutaneously to accelerate atrial remodeling. RAP+DOCA resulted in increased AF stability with earlier onset of sustained AF and accelerated anatomical atrial remodeling with more pronounced LA dilatation. This novel porcine model can serve to characterize effects of maladaptive stimuli or protective interventions specifically during early AF. PMID:26803554

  12. Structural and functional annotation of the porcine immunome

    PubMed Central

    2013-01-01

    Background The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. Results The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated

  13. Changes in leukocyte subsets of pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In spite of more than two decades of extensive research, the understanding of porcine reproductive and respiratory syndrome virus (PRRSv) immunity is still incomplete. A PRRSv infection of the late term pregnant female can result in abortions, early farrowings, fetal death, and the birth of weak, co...

  14. Characterization of ventricular depolarization and repolarization changes in a porcine model of myocardial infarction.

    PubMed

    Romero, Daniel; Ringborn, Michael; Demidova, Marina; Koul, Sasha; Laguna, Pablo; Platonov, Pyotr G; Pueyo, Esther

    2012-12-01

    In this study, several electrocardiogram (ECG)-derived indices corresponding to both ventricular depolarization and repolarization were evaluated during acute myocardial ischemia in an experimental model of myocardial infarction produced by 40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly observed from minute 4 after the start of coronary occlusion, achieving their maximum values between 11 and 22 min for depolarization and between 9 and 12 min for repolarization indices, respectively. Subsequently, these maximum changes started to decrease during the latter part of the occlusion. Depolarization changes associated with the second half of the QRS complex showed a significant but inverse correlation with the myocardium at risk (MaR) estimated by scintigraphic images. The correlation between MaR and changes of the downward slope of the QRS complex, [Formula: see text], evaluated at the two more relevant peaks observed during the occlusion, was r = -0.75, p < 0.01 and r = -0.79, p < 0.01 for the positive and negative deflections observed in [Formula: see text], temporal evolution, respectively. Repolarization changes, analyzed by evaluation of ST segment elevation at the main observed positive peak, also showed negative, however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results suggest that changes evaluated in the latter part of the depolarization, such as those described by [Formula: see text], which are influenced by R-wave amplitude, QRS width and ST level variations simultaneously, correlate better with the amount of ischemia than other indices evaluated in the earlier part of depolarization or during the ST segment.

  15. Physical and Mathematical Modeling in Experimental Papers.

    PubMed

    Möbius, Wolfram; Laan, Liedewij

    2015-12-17

    An increasing number of publications include modeling. Often, such studies help us to gain a deeper insight into the phenomena studied and break down barriers between experimental and theoretical communities. However, combining experimental and theoretical work is challenging for authors, reviewers, and readers. To help maximize the usefulness and impact of combined theoretical and experimental research, this Primer describes the purpose, usefulness, and different types of models and addresses the practical aspect of integrated publications by outlining characteristics of good modeling, presentation, and fruitful collaborations.

  16. Physical and Mathematical Modeling in Experimental Papers.

    PubMed

    Möbius, Wolfram; Laan, Liedewij

    2015-12-17

    An increasing number of publications include modeling. Often, such studies help us to gain a deeper insight into the phenomena studied and break down barriers between experimental and theoretical communities. However, combining experimental and theoretical work is challenging for authors, reviewers, and readers. To help maximize the usefulness and impact of combined theoretical and experimental research, this Primer describes the purpose, usefulness, and different types of models and addresses the practical aspect of integrated publications by outlining characteristics of good modeling, presentation, and fruitful collaborations. PMID:26687351

  17. The pig as a model for translational research: overview of porcine animal models at Jichi Medical University.

    PubMed

    Kobayashi, Eiji; Hishikawa, Shuji; Teratani, Takumi; Lefor, Alan T

    2012-01-01

    To improve the welfare of experimental animals, investigators seek to respect the 3R principle (Replacement, Reduction, and Refinement). Even when large animal studies are essential before moving to clinical trials, it is important to look for ways to reduce the number of experimental animals used. At the Center for the Development of Advanced Medical Technology, we consider 'medical' pigs to be ideal preclinical model systems.We have been using both wild-type and genetically modified pigs. We began using this approach about 10 years ago with a 'total pig system' to model human health and disease for the purposes of both medical skill education and the development of new devices and therapeutic strategies.At our Center, medical students and residents use pigs to gain experience with surgical skills and train for emergency procedures after appropriate simulation training. Senior clinicians have also used these models to advance the development of innovative tools for endo- and laparoscopic procedures. The Center focuses on translational research for organ transplantation and stem cell therapy. Several pig models have been established for liver, intestine, kidney, pancreas, and lung transplantation. Mesenchymal stromal cells have been established in green fluorescent protein- and red fluorescent protein-transgenic pigs and tested to trans-differentiate organogenesis. A program to establish induced pluripotent stem cells in the pig is ongoing at our Center.Here, we review our 10 years of activity in this field. Based on our experience in surgical education and research, experimental pigs are valuable models in translational research.

  18. Comparative analysis of in situ versus ex situ perfusion on flow and microcirculation in kidney procurement: research on a porcine model

    PubMed Central

    2013-01-01

    Background The first crucial step in transplantation appears to be the effective rinsing of the graft during organ procurement. Even though there is strong suspicion that ex situ perfusion results in better rinsing of the graft, there is no proof for this hypothesis. The aim of this study was to analyse the differences of in situ and ex situ kidney perfusion in a porcine model. Methods Standardised multiorgan procurement was performed in 15 German landrace pigs. Perfusion was carried out using histidine–tryptophan–ketoglutarate solution (HTK) under the application of pressure. In one kidney, in situ perfusion via the aorta was carried out while the second kidney received ex situ perfusion via the renal artery (RA). Perfusate flow inside the aorta and the RA was recorded at different pressure steps. In order to visualise the effect on the microcirculation, different coloured microparticles (MPs; 10 μm) were administered via the aorta or RA. Subsequently, frozen sections of the explanted kidneys were analysed histologically and MPs were evaluated quantitatively. Results Ex situ kidney perfusion resulted in significantly improved flow rates (P<0.0001) compared with in situ perfusion. By applying ex situ perfusion it was even possible to attain physiological flow levels on the RA under the application of external pressure of 150 to 200 mmHg. The amount of MPs was able to highlight the positive impact of ex situ perfusion on microcirculation of the kidney graft (P<0.0001). Conclusions The use of MPs represents a valuable tool for quantitative investigation and illustration of kidney perfusion in experimental setups. Additional ex situ perfusion is able to improve the quality of kidney perfusion. PMID:23837545

  19. Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices – an experimental study in the rat

    PubMed Central

    2014-01-01

    Introduction Within the last decades, collagen types I and III have been established as a sufficient biomaterial for GBR and GTR procedures. They might also be an adequate matrix for soft tissue augmentations. However, collagen materials differ significantly regarding resorption time, biodegradation pattern and the invasion of inflammatory cells. The aim of the present study was to compare the biodegradation and tissue integration of native, differently processed and cross-linked collagen scaffolds in rats. Methods Four experimental porcine collagen matrices of 1.0 mm thickness, developed for soft tissue augmentation procedures, were tested. Based on the same native dermal Type I and III collagen, native (ND, Mucoderm® prototype), specifically defatted (DD), ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL) dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two specimens of 1 × 1 cm were fixed around a non-absorbable spacer using non-absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each. After each period, eight rats were sacrificed and explanted specimens were prepared for histological analysis. The following parameters were evaluated: membrane thickness as a sign of biodegradation and volume stability, cell ingrowth, vascularization, tissue integration and foreign body reaction. Results Biodegradation pattern of the non cross-linked collagen scaffolds differed only slightly in terms of presence of inflammatory cells and cell invasion into the matrix. In terms of biodegradation, ECL displayed a considerable slower resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide showed a significant higher invasion of inflammatory cells. Conclusion Within the limits of the present study it was concluded that the

  20. Efficacy of a bio-electric dressing in healing deep, partial-thickness wounds using a porcine model .

    PubMed

    Harding, Andrew C; Gil, Joel; Valdes, Jose; Solis, Michael; Davis, Stephen C

    2012-09-01

    Numerous physical modalities have been used in attempts to augment the healing process, including ultrasound, low- energy light therapy, and electrical stimulation (ES). ES has been shown to benefit tissue repair in a variety of wound types, but variations in study designs, administration, and parameters render its application in clinical practice somewhat unconventional. A dressing was designed to generate an electric potential of 0.6 V to 0.7 V in the presence of moisture, thereby delivering a sustained micro-current without the need for an external power source. The purpose of this study was to examine the effects of this bio-electric dressing (BED) on deep, partial-thickness wounds using six female specific pathogen-free animals and a well established porcine model for wound healing. Wounds (10 mm x 7 mm x 0.5 mm) were created in paravertebral and thoracic areas of these animals using a specialized electrokeratome and covered with the active polyester BED and a polyurethane film dressing (n = 30) (treatment) or an inactive polyester and film dressing (n = 30). Using an epidermal migration assay, wounds were assessed daily from day 4 through day 8 post-wounding. Differences in the proportion of wounds healed were statistically significant (P <0.001) on days 5 and 6 post-wounding. These results show BED is more effective than a control dressing treatment with moisture-retentive dressings in this animal model. Controlled clinical studies are warranted to elucidate the potential clinical implications of this treatment modality.

  1. An In Vivo Comparison of Hemostatic Gelatin Matrix Products in a Porcine Spleen Biopsy-punch Model.

    PubMed

    Hutchinson, Richard W; Werrlein, Stephanie; Johns, Douglas B; Zhang, Gary; Clymer, Jeffrey W; Kocharian, Richard

    2015-11-01

    Flowable gelatin matrix products have established themselves as effective, easy-to-use hemostatic agents useful in a variety of surgical situations. A recently reformulated gelatin matrix, Surgiflo® (Ethicon Inc., Somerville, NJ), can be prepared quickly and provides consistent flow over an 8-hr. period. No in vivo studies have yet been reported comparing hemostasis with the new Surgiflo to other currently marketed flowable gelatin matrix products. This study was conducted to determine whether Surgiflo in actual use has hemostatic qualities different from another commercial gelatin matrix. An in vivo model based on porcine spleen biopsy punch-induced bleeding was used to compare Surgiflo and Floseal™ (Baxter Healthcare Corporation, Hayward, CA), both with thrombin. Time required to achieve hemostasis and proportion of sites achieving hemostasis within 30 s were determined for both hemostatic agents and a control of saline-soaked gauze. Results were stratified by the degree of initial bleeding (mild, moderate, severe). Hemostasis was achieved within 3 minutes at all sites for both test products regardless of level of initial bleeding, and control sites continued bleeding past 10 minutes. There were no statistically significant differences between Surgiflo and Floseal for either mean time to hemostasis or proportion of sites hemostatic within 30 s. In this realistic in vivo model both gelatin matrix products were effective, and there were no significant differences observed in hemostatic efficacy between Surgiflo and Floseal. Other factors, such as ease of preparation and application, in-use stability, and economic considerations may affect a surgeon's decision in selection of a desirable hemostatic product.

  2. Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock.

    PubMed

    Bambakidis, Ted; Dekker, Simone E; Sillesen, Martin; Liu, Baoling; Johnson, Craig N; Jin, Guang; de Vries, Helga E; Li, Yongqing; Alam, Hasan B

    2016-08-15

    Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2 h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300 mg/kg, n = 5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis® (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p < 0.001), natural killer cell communication (p < 0.001), and dendritic cell maturation (p < 0.001). DAVID analysis indicated that a cluster of inflammatory pathways held the highest rank and gene enrichment score. Real-time PCR data confirmed that VPA significantly down-expressed genes that ultimately regulate nuclear factor-kB (NF-kB)-mediated production of cytokines, such as TYROBP, TREM2, CCR1, and IL-1β. This high-throughput analysis of cerebral gene expression shows that addition of VPA to the resuscitation protocol significantly modulates the expression of inflammatory pathways in a clinically realistic model of TBI+HS. PMID:26905959

  3. Succinobucol-Eluting Stents Increase Neointimal Thickening and Peri-Strut Inflammation in a Porcine Coronary Model

    PubMed Central

    Watt, Jonathan; Kennedy, Simon; McCormick, Christopher; Agbani, Ejaife O; McPhaden, Allan; Mullen, Alexander; Czudaj, Peter; Behnisch, Boris; Wadsworth, Roger M; Oldroyd, Keith G

    2013-01-01

    Objective The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model. Background: Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties. Methods Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS). Results The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05). Conclusion In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting. © 2012 Wiley Periodicals, Inc. PMID:22581717

  4. Modelling from the experimental developmental biologists viewpoint.

    PubMed

    Economou, Andrew D; Green, Jeremy B A

    2014-11-01

    In this review we consider Reaction-Diffusion as the archetype of a model in developmental biology. We consider its history in relation to experimental work since it was first proposed in 1952 by Turing and revived in the 1970s by Meinhardt. We then discuss the most recent examples of experiments that address this model, including the challenges that remain in capturing the physico-chemical manifestation of the model mechanism in a real developmental system. Finally we discuss the model's current status and use in the experimental community. PMID:25026465

  5. Experimental Modeling of Proliferative Vitreoretinopathy. An Experimental Morphological Study.

    PubMed

    Khoroshilova-Maslova, I P; Leparskaya, N L; Nabieva, M M; Andreeva, L D

    2015-05-01

    A model of proliferative vitreoretinopathy induced by simultaneous intravitreal injection of recombinant IL-1β and platelet concentrate is created and its main morphological manifestations are studied on Chinchilla rabbits. The model reflects pathogenesis of proliferative vitreoretinopathy: epiretinal membrane with the formation of retinal plication, traction detachment of the retina; moderate inflammatory reaction in the uveal tract, in the optic nerve infundibulum, in the vitreous body; intact structural elements of the retina, dissociation of the retinal pigmented epithelium cells with their subsequent migration. The model is adequate to the clinical picture of proliferative vitreoretinopathy in humans, which recommends it for experimental studies of the efficiency of drug therapy and prevention of this disease. PMID:26033599

  6. Impact of Cardiopulmonary Bypass on Respiratory Mucociliary Function in an Experimental Porcine Model

    PubMed Central

    Sánchez-Véliz, Rodrigo; Carmona, Maria José; Otsuki, Denise Aya; Freitas, Claudia; Benício, Anderson; Negri, Elnara Marcia; Malbouisson, Luiz Marcelo

    2015-01-01

    Background The impact of cardiac surgery using cardiopulmonary bypass (CPB) on the respiratory mucociliary function is unknown. This study evaluated the effects of CPB and interruption of mechanical ventilation on the respiratory mucociliary system. Methods Twenty-two pigs were randomly assigned to the control (n = 10) or CPB group (n = 12). After the induction of anesthesia, a tracheostomy was performed, and tracheal tissue samples were excised (T0) from both groups. All animals underwent thoracotomy. In the CPB group, an aorto-bicaval CPB was installed and maintained for 90 minutes. During the CPB, mechanical ventilation was interrupted, and the tracheal tube was disconnected. A second tracheal tissue sample was obtained 180 minutes after the tracheostomy (T180). Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo tracheal epithelium. Mucus viscosity (MV) was assessed using a cone-plate viscometer. Qualitative tracheal histological analysis was performed at T180 tissue samples. Results CBF decreased in the CPB group (13.1 ± 1.9 Hz vs. 11.1 ± 2.1 Hz, p < 0.05) but not in the control group (13.1 ± 1 Hz vs. 13 ± 2.9 Hz). At T90, viscosity was increased in the CPB group compared to the control (p < 0.05). No significant differences were observed in in situ MCT. Tracheal histology in the CPB group showed areas of ciliated epithelium loss, submucosal edema and infiltration of inflammatory cells. Conclusion CPB acutely contributed to alterations in tracheal mucocilliary function. PMID:26288020

  7. Improving the physiological realism of experimental models.

    PubMed

    Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

    2016-04-01

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease. PMID:27051507

  8. Improving the physiological realism of experimental models.

    PubMed

    Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

    2016-04-01

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

  9. 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.

    PubMed

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

    2015-01-01

    Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system in the perspective of genital Chlamydia infection. The comparison of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, only showing a slight difference in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4(+)/CD8(+) double positive T cells. The genital immune system is also very similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa - predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in Göttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5-5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital Chlamydia infection. PMID:26411309

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

    PubMed

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

    2015-09-28

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

  11. Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model

    PubMed Central

    Zentai, Christian; Solomon, Cristina; van der Meijden, Paola E. J.; Spronk, Henri M. H.; Schnabel, Jonas; Rossaint, Rolf

    2015-01-01

    Introduction: In a 24-hour porcine model of liver injury, we showed that fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis. Here we report data from the same study showing the impact of fibrinogen on coagulation variables. Materials and Methods: Coagulopathy was induced in 20 German land race pigs by hemodilution and blunt liver injury. Animals randomly received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters were assessed and thromboelastometry (ROTEM) was performed. Results: Fibrinogen concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM clot formation time, and prothrombin time induced by hemodilution and liver injury. A decrease in clot strength was also ameliorated. Endogenous thrombin potential was significantly higher in the fibrinogen group than in the control group, 20 minutes (353 ± 24 vs 289 ± 22 nmol/L·min; P < .05) and 100 minutes (315 ± 40 vs 263 ± 38 nmol/L·min; P < .05) after the start of infusion. However, no significant between-group differences were seen in other thrombin generation parameters or in d-dimer or thrombin–antithrombin levels. Fibrinogen–platelet binding was reduced following liver injury, with no significant differences between groups. No significant between-group differences were observed in any parameter at ∼12 and ∼24 hours. Conclusion: This study suggests that, in trauma, fibrinogen supplementation may shorten some measurements of the speed of coagulation initiation and produce a short-lived increase in endogenous thrombin potential, potentially through increased clotting substrate availability. Approximately 12 and 24 hours after starting fibrinogen concentrate/saline infusion, all parameters measured in this study were comparable in the 2 study groups. PMID:25948634

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

    PubMed Central

    Shi, Haifeng; Li, Ruokun; Qiang, Jinwei; Li, Ying; Wang, Li; Sun, Rongxun

    2016-01-01

    Objective To evaluate multi-slice computed tomography (CT) perfusion imaging (CTPI) for identifying microcirculatory dysfunction in small intestinal ischemia−reperfusion (IR) injury in a porcine model. Materials and Methods Fifty-two pigs were randomly divided into 4 groups: (1) the IR group (n = 24), where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA) for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively); (2) the sham-operated (SO) group (n = 20), where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively); (3) the ischemia group (n = 4), where the SMA was separated and clamped for 2 h, without reperfusion, and (4) baseline group (n = 4), an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) and for histopathological examination. Results The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia). The blood flow (BF), blood volume (BV), and permeability surface (PS) among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion. Conclusion CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury. PMID:27458696

  13. 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

    PubMed Central

    2012-01-01

    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 modulations point to

  14. Transitional Employment Experimental Model (TEEM). Final Report.

    ERIC Educational Resources Information Center

    California State Personnel Board, Sacramento.

    The final report of the Transitional Employemnt Experimental Model (TEEM) Project, a research and development project providing a potential model for a large scale manpower absorption program in times of economic need, is presented. One major purpose of the project was to demonstrate the viability of providing suitable job placement for the…

  15. Comparing fluid mechanics models with experimental data.

    PubMed Central

    Spedding, G R

    2003-01-01

    The art of modelling the physical world lies in the appropriate simplification and abstraction of the complete problem. In fluid mechanics, the Navier-Stokes equations provide a model that is valid under most circumstances germane to animal locomotion, but the complexity of solutions provides strong incentive for the development of further, more simplified practical models. When the flow organizes itself so that all shearing motions are collected into localized patches, then various mathematical vortex models have been very successful in predicting and furthering the physical understanding of many flows, particularly in aerodynamics. Experimental models have the significant added convenience that the fluid mechanics can be generated by a real fluid, not a model, provided the appropriate dimensionless groups have similar values. Then, analogous problems can be encountered in making intelligible but independent descriptions of the experimental results. Finally, model predictions and experimental results may be compared if, and only if, numerical estimates of the likely variations in the tested quantities are provided. Examples from recent experimental measurements of wakes behind a fixed wing and behind a bird in free flight are used to illustrate these principles. PMID:14561348

  16. Experimental and Modeling Studies of Massif Anorthosites

    NASA Technical Reports Server (NTRS)

    Longhi, John

    1999-01-01

    This termination report covers the latter part of a single research effort spanning several grant cycles. During this time there was a single title, "Experimental and Modeling Studies of Massif Anorthosites", but there were several contract numbers as the mode and location of NASA contract administration changed. Initially, the project was funded as an increment to the PI's other grant, "Early Differentiation of the Moon: Experimental and Modeling Studies", but subsequently it became an independent grant. Table 1 contains a brief summary of the dates and contract numbers.

  17. A mathematical model of detection and dynamics of porcine transmissible gastroenteritis.

    PubMed Central

    Hone, J.

    1994-01-01

    Transmissible gastroenteritis (TGE) is a viral disease causing dehydration, diarrhoea and death in pigs. The disease is widespread in pig-producing areas of the world but does not occur in Australia. A mathematical model of TGE spread within a pig herd is proposed and calibrated by reference to published data. The model is then applied to two situations of special interest; first to estimate the delay before detection of TGE (6 to over 30 days) when infection is first introduced into a herd of domestic or feral pigs, and second the effect of the disease in a population of feral pigs (could become endemic if transmission is high). PMID:8062875

  18. Experimental Concepts for Testing Seismic Hazard Models

    NASA Astrophysics Data System (ADS)

    Marzocchi, W.; Jordan, T. H.

    2015-12-01

    Seismic hazard analysis is the primary interface through which useful information about earthquake rupture and wave propagation is delivered to society. To account for the randomness (aleatory variability) and limited knowledge (epistemic uncertainty) of these natural processes, seismologists must formulate and test hazard models using the concepts of probability. In this presentation, we will address the scientific objections that have been raised over the years against probabilistic seismic hazard analysis (PSHA). Owing to the paucity of observations, we must rely on expert opinion to quantify the epistemic uncertainties of PSHA models (e.g., in the weighting of individual models from logic-tree ensembles of plausible models). The main theoretical issue is a frequentist critique: subjectivity is immeasurable; ergo, PSHA models cannot be objectively tested against data; ergo, they are fundamentally unscientific. We have argued (PNAS, 111, 11973-11978) that the Bayesian subjectivity required for casting epistemic uncertainties can be bridged with the frequentist objectivity needed for pure significance testing through "experimental concepts." An experimental concept specifies collections of data, observed and not yet observed, that are judged to be exchangeable (i.e., with a joint distribution independent of the data ordering) when conditioned on a set of explanatory variables. We illustrate, through concrete examples, experimental concepts useful in the testing of PSHA models for ontological errors in the presence of aleatory variability and epistemic uncertainty. In particular, we describe experimental concepts that lead to exchangeable binary sequences that are statistically independent but not identically distributed, showing how the Bayesian concept of exchangeability generalizes the frequentist concept of experimental repeatability. We also address the issue of testing PSHA models using spatially correlated data.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock.

    PubMed

    Palágyi, Péter; Kaszaki, József; Rostás, Andrea; Érces, Dániel; Németh, Márton; Boros, Mihály; Molnár, Zsolt

    2015-01-01

    Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n = 9) and shock groups (n = 27). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60-180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r = -0.65, p < 0.0001), CPR (r = -0.64, p < 0.0001), central venous oxygen saturation (r = -0.50, p < 0.0001), and central venous-to-arterial PCO2 difference (r = 0.62, p < 0.0001). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock. PMID:26504837

  1. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock

    PubMed Central

    Palágyi, Péter; Kaszaki, József; Rostás, Andrea; Érces, Dániel; Németh, Márton; Boros, Mihály; Molnár, Zsolt

    2015-01-01

    Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n = 9) and shock groups (n = 27). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r = −0.65, p < 0.0001), CPR (r = −0.64, p < 0.0001), central venous oxygen saturation (r = −0.50, p < 0.0001), and central venous-to-arterial PCO2 difference (r = 0.62, p < 0.0001). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock. PMID:26504837

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

    SciTech Connect

    Planche, Olivier; Teriitehau, Christophe; Boudabous, Sana; Robinson, Joey Marie; Rao, Pramod; Deschamps, Frederic; Farouil, Geoffroy; Baere, Thierry de

    2013-02-15

    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.

  3. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research.

  4. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research. PMID:26743051

  5. Optimal Experimental Design for Model Discrimination

    PubMed Central

    Myung, Jay I.; Pitt, Mark A.

    2009-01-01

    Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it possible to determine these values, and thereby identify an optimal experimental design. After describing the method, it is demonstrated in two content areas in cognitive psychology in which models are highly competitive: retention (i.e., forgetting) and categorization. The optimal design is compared with the quality of designs used in the literature. The findings demonstrate that design optimization has the potential to increase the informativeness of the experimental method. PMID:19618983

  6. Influence of Chest Compressions on Circulation during the Peri-Cardiac Arrest Period in Porcine Models

    PubMed Central

    Li, Yan; Walline, Joseph; Zheng, Liangliang; Fu, Yangyang; Yao, Dongqi; Zhu, Huadong; Liu, Xiaohe; Chai, Yanfen; Wang, Zhong; Yu, Xuezhong

    2016-01-01

    Objective Starting chest compressions immediately after a defibrillation shock might be harmful, if the victim already had a return of spontaneous circulation (ROSC) and yet was still being subjected to external compressions at the same time. The objective of this study was to study the influence of chest compressions on circulation during the peri-cardiac arrest period. Design Prospective, randomized controlled study. Setting Animal experimental center in Peking Union Medical Collage Hospital, Beijing, China. Subjects Healthy 3-month-old male domestic pigs. Interventions 44 pigs (28±2 kg) were randomly assigned to three groups: Group I (non-arrested with compressions) (n = 12); Group II (arrested with compressions only) (n = 12); Group III (ROSC after compressions and defibrillation) (n = 20). In Groups I and II, compressions were performed to a depth of 5cm (Ia and IIa, n = 6) or a depth of 3cm (Ib and IIb, n = 6) respectively, while in Group III, the animals which had just achieved ROSC (n = 18) were compressed to a depth of 5cm (IIIa, n = 6), a depth of 3cm (IIIb, n = 6), or had no compressions (IIIc, n = 6). Hemodynamic parameters were collected and analyzed. Measurements and Findings Hemodynamics were statistically different between Groups Ia and Ib when different depths of compressions were performed (p < 0.05). In Group II, compressions were beneficial and hemodynamics correlated with the depth of compressions (p < 0.05). In Group III, compressions that continued after ROSC produced a reduction in arterial pressure (p < 0.05). Conclusions Chest compressions might be detrimental to hemodynamics in the early post-ROSC stage. The deeper the compressions were, the better the effect on hemodynamics during cardiac arrest, but the worse the effect on hemodynamics after ROSC. PMID:27168071

  7. Optimal Experimental Design for Model Discrimination

    ERIC Educational Resources Information Center

    Myung, Jay I.; Pitt, Mark A.

    2009-01-01

    Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it…

  8. Establishment of a novel, eco-friendly transgenic pig model using porcine pancreatic amylase promoter-driven fungal cellulase transgenes.

    PubMed

    Lin, Y S; Yang, C C; Hsu, C C; Hsu, J T; Wu, S C; Lin, C J; Cheng, W T K

    2015-02-01

    Competition between humans and livestock for cereal and legume grains makes it challenging to provide economical feeds to livestock animals. Recent increases in corn and soybean prices have had a significant impact on the cost of feed for pig producers. The utilization of byproducts and alternative ingredients in pig diets has the potential to reduce feed costs. Moreover, unlike ruminants, pigs have limited ability to utilize diets with high fiber content because they lack endogenous enzymes capable of breaking down nonstarch polysaccharides into simple sugars. Here, we investigated the feasibility of a transgenic strategy in which expression of the fungal cellulase transgene was driven by the porcine pancreatic amylase promoter in pigs. A 2,488 bp 5'-flanking region of the porcine pancreatic amylase gene was cloned by the genomic walking technique, and its structural features were characterized. Using GFP as a reporter, we found that this region contained promoter activity and had the potential to control heterologous gene expression. Transgenic pigs were generated by pronuclear microinjection. Founders and offspring were identified by PCR and Southern blot analyses. Cellulase mRNA and protein showed tissue-specific expression in the pancreas of F1 generation pigs. Cellulolytic enzyme activity was also identified in the pancreas of transgenic pigs. These results demonstrated the establishment of a tissue-specific promoter of the porcine pancreatic amylase gene. Transgenic pigs expressing exogenous cellulase may represent a way to increase the intake of low-cost, fiber-rich feeds.

  9. Cholestasis: human disease and experimental animal models.

    PubMed

    Rodríguez-Garay, Emilio Alberto

    2003-01-01

    Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common. Other types of cholestasis seen in humans are a group of familial cholestatic disorders, obstructive cholestasis, primary biliary cirrhosis, extrahepatic biliary atresia, primary sclerosing cholangitis, cholestasis of pregnancy, oral contraceptive-induced cholestasis, and sepsis-induced cholestasis. Experimental animal models allow the understanding of pathophysiological mechanisms involved and their clinical correlates. The most common experimental models of intrahepatic cholestasis are estrogen-induced, endotoxin-induced and drug-induced cholestasis. A well known model of extrahepatic biliary obstruction is common bile duct ligation. Drug-induced cholestasis were described using different drugs. On this regard, alpha naphthylisothiocyanate treatment has been extensively used, permitting to describe not only cholestatic alterations but also compensatory mechanisms. Congenital defficiency of transport proteins also were studied in natural rat models of cholestasis. The experimental animal models allow to define down-regulated alterations of hepatocyte transport proteins, and up-regulated ones acting as compensatory mechanisms. In conclusion, animal model and transport protein studies are necessary for the progressive understanding of congenital and acquired human cholestasis, and regulatory mechanisms that operate on liver cells.

  10. Porcine Sialoadhesin: A Newly Identified Xenogeneic Innate Immune Receptor

    PubMed Central

    Brock, Linda G.; Delputte, Peter L.; Waldman, Joshua P.; Nauwynck, Hans J.; Rees, Michael A.

    2012-01-01

    Extracorporeal porcine liver perfusion is being developed as a bridge to liver allotransplantation for patients with fulminant hepatic failure. This strategy is limited by porcine Kupffer cell destruction of human erythrocytes, mediated by lectin binding of a sialic acid motif in the absence of antibody and complement. Sialoadhesin, a macrophage restricted lectin that binds sialic acid, was originally described as a sheep erythrocyte binding receptor. Given similarities between sialoadhesin and the unidentified macrophage lectin in our model, we hypothesized porcine sialoadhesin contributed to recognition of human erythrocytes. Two additional types of macrophages were identified to bind human erythrocytes - spleen and alveolar. Expression of sialoadhesin was confirmed by immunofluorescence in porcine tissues and by flow cytometry on primary macrophages. A stable transgenic cell line expressing porcine sialoadhesin (pSn CHO) bound human erythrocytes, while a sialoadhesin mutant cell line did not. Porcine macrophage and pSn CHO recognition of human erythrocytes was inhibited approximately 90% by an anti-porcine sialoadhesin monoclonal antibody and by human erythrocyte glycoproteins. Furthermore, this binding was substantially reduced by sialidase treatment of erythrocytes. These data support the hypothesis that porcine sialoadhesin is a xenogeneic receptor that mediates porcine macrophage binding of human erythrocytes in a sialic acid-dependent manner. PMID:22958948

  11. Magnetic sentinel lymph node biopsy and localization properties of a magnetic tracer in an in vivo porcine model.

    PubMed

    Anninga, Bauke; Ahmed, Muneer; Van Hemelrijck, Mieke; Pouw, Joost; Westbroek, David; Pinder, Sarah; Ten Haken, Bennie; Pankhurst, Quentin; Douek, Michael

    2013-08-01

    The standard for the treatment of early non-palpable breast cancers is wide local excision directed by wire-guided localization and sentinel lymph node biopsy (SLNB). This has drawbacks technically and due to reliance upon radioisotopes. We evaluated the use of a magnetic tracer for its localization capabilities and concurrent performance of SLNB using a handheld magnetometer in a porcine model as a novel alternative to the current standard. Ethical approval by the IRCAD Ethics Review Board, Strasbourg (France) was received. A magnetic tracer was injected in varying volumes (0.1-5 mL) subcutaneously into the areolar of the left and right 3rd inguinal mammary glands in 16 mini-pigs. After 4 h magnetometer counts were taken at the injection sites and in the groins. The magnetometer was used to localize any in vivo signal from the draining inguinal lymph nodes. Magnetic SLNB followed by excision of the injection site was performed. The iron content of sentinel lymph nodes (SLNs) were graded and quantified. All excised specimens were weighed and volumes were calculated. Univariate analyses were performed to evaluate correlation. Magnetic SLNB was successful in all mini-pigs. There was a significant correlation (r = 0.86; p < 0.01) between magnetometer counts and iron content of SLNs. Grading of SLNs on both H&E and Perl's staining correlated significantly with the iron content (p = 0.001; p = 0.003) and magnetometer counts (p < 0.001; p = 0.004). The peak counts corresponded to the original magnetic tracer injection sites 4 h after injection in all cases. The mean volume and weight of excised injection site specimens was 2.9 cm(3) (SD 0.81) and 3.1 g (SD 0.85), respectively. Injection of ≥0.5 mL magnetic tracer was associated with significantly greater volume (p = 0.05) and weight of excision specimens (p = 0.01). SLNB and localization can be performed in vivo using a magnetic tracer. This could provide a viable alternative for lesion localization and concurrent SLNB

  12. Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

    PubMed Central

    Hanawa, Kenichiro; Ito, Kenta; Aizawa, Kentaro; Shindo, Tomohiko; Nishimiya, Kensuke; Hasebe, Yuhi; Tuburaya, Ryuji; Hasegawa, Hideyuki; Yasuda, Satoshi; Kanai, Hiroshi; Shimokawa, Hiroaki

    2014-01-01

    Background Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD. Methods and Results We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group. Conclusions These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. PMID:25111309

  13. Experimental and model analysis on the temperature dynamics during diode laser welding of the cornea.

    PubMed

    Rossi, Francesca; Pini, Roberto; Menabuoni, Luca

    2007-01-01

    Corneal laser welding is a technique used clinically to induce the immediate sealing of corneal wounds. We present an experimental and model analysis of the temperature dynamics during diode laser-induced corneal welding, which is aimed at characterizing the mechanism of tissue fusion. Ex vivo tests were performed on porcine eyes in the typical irradiation conditions used for laser-induced suturing in cornea transplant. Three laser power densities (12.5 W/cm(2), 16.7 W/cm(2), 20.8 W/cm(2)) were tested. The superficial temperature of the cornea was measured by means of an infrared thermocamera. Experimental data were compared with the results of a three-dimensional (3D) model of a laser-welding process in the cornea, solved by the use of the Finite Element Method (FEM). The model solution and experimental results showed good agreement. The model was thus used to estimate the temperature enhancement inside the corneal wound and to calculate the thermal damage inside the tissue. The results indicated a selective, spatially confined heating effect that occurred at operative temperatures (59 to 66 degrees C) close to intermediate denaturation points of the stromal collagen, before its complete disorganization. No significant heat damage to the region of the laser-treated wound was evidenced in the operative irradiation conditions of corneal welding.

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

    PubMed

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

    2014-05-19

    Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm(2) ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p < 0.001) and control (41 ± 4%, p = 0.012) groups. LVEF markedly improved in shock-wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Amniotic Fluid-Derived Mesenchymal Stem Cells Prevent Fibrosis and Preserve Renal Function in a Preclinical Porcine Model of Kidney Transplantation

    PubMed Central

    Baulier, Edouard; Favreau, Frederic; Le Corf, Amélie; Jayle, Christophe; Schneider, Fabrice; Goujon, Jean-Michel; Feraud, Olivier; Bennaceur-Griscelli, Annelise; Turhan, Ali G.

    2014-01-01

    It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation. PMID:24797827

  16. Primary in vitro culture of porcine tracheal epithelial cells in an air-liquid interface as a model to study airway epithelium and Aspergillus fumigatus interactions.

    PubMed

    Khoufache, Khaled; Cabaret, Odile; Farrugia, Cécile; Rivollet, Danièle; Alliot, Annie; Allaire, Eric; Cordonnier, Catherine; Bretagne, Stéphane; Botterel, Françoise

    2010-12-01

    Since the airway epithelium is the first tissue encountered by airborne fungal spores, specific models are needed to study this interaction. We developed such a model using primary porcine tracheal epithelial cells (PTEC) as a possible alternative to the use of primary human cells. PTEC were obtained from pigs and were cultivated in an air-liquid interface. Fluorescent brightener was employed to quantify the internalization of Aspergillus fumigatus conidia. Potential differences (Vt) and transepithelial resistances (Rt) after challenge with the mycotoxin, verruculogen, were studied. Primers for porcine inflammatory mediator genes IL-8, TNF-alpha, and GM-CSF were designed for a quantitative real-time PCR procedure to study cellular responses to challenges with A. fumigatus conidia. TEM showed the differentiation of ciliated cells and the PTEC ability to internalize conidia. The internalization rate was 21.9 ± 1.4% after 8 h of incubation. Verruculogen (10(-6) M) significantly increased Vt without having an effect on the Rt. Exposure of PTEC to live A. fumigatus conidia for 24 h induced a 10- to 40-fold increase in the mRNA levels of inflammatory mediator genes. PTEC behave similarly to human cells and are therefore a suitable alternative to human cells for studying interaction between airway epithelium and A. fumigatus. PMID:20608777

  17. Cryopreservation of germinal vesicle stage porcine oocytes based on intracellular ice formation assessment.

    PubMed

    Yang, C Y; Chen, M C; Lee, P T; Lin, T T

    2012-01-01

    This study aimed at evaluating the feasibility of slow freezing for cryopreservation of germinal vesicle (GV) stage porcine oocytes. In this study, intracellular ice formation (IIF) characteristics of GV porcine oocytes were investigated by using a thermoelectric cooling (TEC) cryomicroscope system. This cryomicroscope system used a thermoelectric cooling (TEC) chip in its cold stage as a heat sink and employed a PID control algorithm to achieve accurate temperature control. The temperature was controlled to a range between 70 degree C and -55 degree C with an accuracy of +/- 0.5 degree C. Five constant cooling rates of 24, 12, 6, 3 and 1.5 degree C/min were tested in experiments in freezing GV porcine oocytes from 20 degree C to -50 degree C in an NCSU-23 medium plus 2.0 M DMSO. The IIF temperature of each individual oocyte was recorded and cumulative IIF probabilities were calculated for each cooling rate. The total cumulative probabilities of IIF temperature distribution were 100 percent, 100 percent, 50.0 percent, 54.3 percent and 58.6 percent at cooling rates of 24, 12, 6, 3 and 1.5 degree C/min, respectively. A Weibull distribution model was found to adequately describe the distribution of IIF temperatures of GV porcine oocytes for the cooling rates tested (R2 = 0.858 +/- 0.09). The IIF experimental results indicate that cooling rates of 6, 3 and 1.5°C/min could be considered as possible cryopreservation protocols. Further experiments were performed to examine the feasibility of using these protocols to cryopreserve GV porcine oocytes. After 44 h of in-vitro maturation in NCSU-23, the survival of thawed oocytes was checked. Porcine oocytes developed from the GV stage to the MII stage by using Hoechst 33258 staining, followed by Lacmoid staining as a secondary check. Normalized survival rates of 37.7 +/- 4.6 percent, 45.0 4.4 percent and 45.4 +/- 5.9 percent were obtained for GV oocytes frozen at 1.5, 3 and 6 degree C/min, respectively. The experimental

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

    PubMed Central

    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

  19. Inflammation in response to n3 fatty acids in a porcine obesity model.

    PubMed

    Faris, Richard J; Boddicker, Rebecca L; Walker-Daniels, Jennifer; Li, Jenny; Jones, Douglas E; Spurlock, Michael E

    2012-12-01

    Fatty acids have distinct cellular effects related to inflammation and insulin sensitivity. Dietary saturated fat activates toll-like receptor 4, which in turn can lead to chronic inflammation, insulin resistance, and adipose tissue macrophage infiltration. Conversely, n3 fatty acids are generally antiinflammatory and promote insulin sensitivity, in part via peroxisome proliferator-activated receptor γ. Ossabaw swine are a useful biomedical model of obesity. We fed Ossabaw pigs either a low-fat control diet or a diet containing high-fat palm oil with or without additional n3 fatty acids for 30 wk to investigate the effect of saturated fats and n3 fatty acids on obesity-linked inflammatory markers. The diet did not influence the inflammatory markers C-reactive protein, TNFα, IL6, or IL12. In addition, n3 fatty acids attenuated the increase in inflammatory adipose tissue CD16(-)CD14(+) macrophages induced by high palm oil. High-fat diets with and without n3 fatty acids both induced hyperglycemia without hyperinsulinemia. The high-fat only group but not the high-fat group with n3 fatty acids showed reduced insulin sensitivity in response to insulin challenge. This effect was not mediated by decreased phosphorylation of protein kinase B. Therefore, in obese Ossabaw swine, n3 fatty acids partially attenuate insulin resistance but only marginally change inflammatory status and macrophage phenotype in adipose tissue.

  20. Macrophages and Uveitis in Experimental Animal Models

    PubMed Central

    Mérida, Salvador; Palacios, Elena; Bosch-Morell, Francisco

    2015-01-01

    Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution. PMID:26078494

  1. Experimental Flow Models for SSME Flowfield Characterization

    NASA Technical Reports Server (NTRS)

    Abel, L. C.; Ramsey, P. E.

    1989-01-01

    Full scale flow models with extensive instrumentation were designed and manufactured to provide data necessary for flow field characterization in rocket engines of the Space Shuttle Main Engine (SSME) type. These models include accurate flow path geometries from the pre-burner outlet through the throat of the main combustion chamber. The turbines are simulated with static models designed to provide the correct pressure drop and swirl for specific power levels. The correct turbopump-hot gas manifold interfaces were designed into the flow models to permit parametric/integration studies for new turbine designs. These experimental flow models provide a vehicle for understanding the fluid dynamics associated with specific engine issues and also fill the more general need for establishing a more detailed fluid dynamic base to support development and verification of advanced math models.

  2. Irradiation Design for an Experimental Murine Model

    SciTech Connect

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-12-07

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

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

    PubMed

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

    2012-08-01

    Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell-based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non-keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts. PMID:22309108

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

    PubMed Central

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

    2015-01-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the dermis upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. PMID:26256624

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed

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

    2015-07-01

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

  8. Laparoscopic Mesh Fixation Using Laser-Assisted Tissue Soldering in a Porcine Model

    PubMed Central

    Soltz, Barbara A.; Stadler, Istvan; Soltz, Robert

    2009-01-01

    Background and Objective: Animal studies using open surgical models indicate that collagen solder is capable of fixation of surgical meshes without interfering with tissue integration, increasing adhesions, or increasing inflammation intraperitoneally. This study describes development of instrumentation and techniques for laparoscopic herniorrhaphy using laser-assisted soldering technology. Study Design and Methods: Anesthetized 20 kg to 25 kg female Yorkshire pigs underwent laparoscopy with a 3-trocar technique. Parietex TET, Parietex TEC, and Prolene mesh segments (5 × 5 cm) were embedded in 55% collagen solder. Segments were inserted by using a specially designed introducer and affixed to the peritoneum by using prototype laser devices (1.45 µ, 4.5 W continuous wave, 5-mm spot, 55° C set temperature) and a custom laparoscopic handpiece (IPOM). Parietex PCO mesh was inserted and affixed using the Endo-hernia stapler (Control). Animals were recovered and underwent second-look laparoscopy at 6 weeks. Mesh sites were harvested after animals were euthanized. Results: The mesh-solder constructs were easily inserted and affixed in an IPOM approach. Prolene mesh tended to curl at its edges as the solder was melted. Postoperative healing was similar to that in Control segments in all cases. Discussion and Conclusion: Collagen-based tissue soldering permits normal wound healing and may mitigate or reduce the use of staples or other foreign bodies for laparoscopic mesh fixation, prevent tissue ischemia and possibly nerve entrapment, which result in severe postoperative pain and morbidity. Laser-assisted mesh fixation is a promising alternative for laparoscopic herniorrhaphy. Further development of this strategy is warranted. PMID:19793465

  9. Acute hematological effects of solar particle event proton radiation in the porcine model.

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2015-07-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. PMID:26256624

  11. Autologous Graft Thickness Affects Scar Contraction and Quality in a Porcine Excisional Wound Model

    PubMed Central

    Rose, Lloyd F.; Wu, Jesse C.; Tucker, David I.; Chan, Maren M.; Christy, Robert J.; Hale, Robert G.; Leung, Kai P.

    2015-01-01

    Background: Texture, color, and durability are important characteristics to consider for skin replacement in conspicuous and/or mobile regions of the body such as the face, neck, and hands. Although autograft thickness is a known determinant of skin quality, few studies have correlated the subjective and objective characters of skin graft healing with their associated morphologic and cellular profiles. Defining these relationships may help guide development and evaluation of future skin replacement strategies. Methods: Six-centimeter-diameter full-thickness wounds were created on the back of female Yorkshire pigs and covered by autografts of variable thicknesses. Skin quality was assessed on day 120 using an observer scar assessment score and objective determinations for scar contraction, erythema, pigmentation, and surface irregularities. Histological, histochemical, and immunohistochemical assessments were performed. Results: Thick grafts demonstrated lower observer scar assessment score (better quality) and decreased erythema, pigmentation, and surface irregularities. Histologically, thin grafts resulted in scar-like collagen proliferation while thick grafts preserves the dermal architecture. Increased vascularity and prolonged and increased cellular infiltration were observed among thin grafts. In addition, thin grafts contained predominately dense collagen fibers, whereas thick grafts had loosely arranged collagen. α-Smooth muscle actin staining for myofibroblasts was observed earlier and persisted longer among thinner grafts. Conclusions: Graft thickness is an important determinant of skin quality. High-quality skin replacements are associated with preserved collagen architecture, decreased neovascularization, and decreased inflammatory cellular infiltration. This model, using autologous skin as a metric of quality, may give a more informative analysis of emerging skin replacement strategies. PMID:26301157

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  13. Prothrombin complex concentrate mitigates diffuse bleeding after cardiopulmonary bypass in a porcine model

    PubMed Central

    Kaspereit, F.; Hoffmann, S.; Pragst, I.; Dickneite, G.

    2010-01-01

    Background Extracorporeal circuit priming and intravascular volume expansion during cardiopulmonary bypass (CPB) may lead to dilutional coagulopathy and excessive diffuse postoperative bleeding. Prothrombin complex concentrate (PCC) containing clotting factors II (FII), VII (FVII), IX (FIX), and X (FX) could be of potential value in correcting dilutional coagulopathy and reducing blood loss. Methods Anaesthetized pigs underwent CPB with hypothermia for 2 h at 25°C followed by 1 h of normothermia. Approximately 1 h after CPB, animals randomly received either isotonic saline 1 ml kg−1 or PCC 30 IU kg−1 in a volume of 1 ml kg−1. Diffuse coagulopathic bleeding was assessed as suture hole blood loss from a Gore-Tex patch placed over a full-thickness incision in the left carotid artery. Results After CPB, levels of FII, FVII, FIX, and FX declined from baseline by 32% to 48%, and PCC fully or partially reversed those deficits. Median suture hole blood loss after administration of saline placebo was 74 ml. PCC reduced suture hole bleeding by a median of 54 ml with a 95% confidence interval of 6–112 ml (P=0.026) compared with saline. PCC, but not saline, normalized skin bleeding time. Peak thrombin generation markedly decreased after CPB, but then returned in PCC-treated animals to a level higher than baseline by 28.7 nM (14.5–41.1 nM; P=0.031). Conclusions PCC was effective in correcting dilutional coagulopathy and reducing diffuse bleeding in an in vivo large-animal CPB model. Further research is warranted on PCC as a haemostatic agent in CPB. PMID:20716565

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-04-01

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

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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

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

    2016-03-21

    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 territory. This ratio was 1.00 ± 0.08 at 70 ke

  18. Experimental "evolutional machines": mathematical and experimental modeling of biological evolution

    NASA Astrophysics Data System (ADS)

    Brilkov, A. V.; Loginov, I. A.; Morozova, E. V.; Shuvaev, A. N.; Pechurkin, N. S.

    Experimentalists possess model systems of two major types for study of evolution continuous cultivation in the chemostat and long-term development in closed laboratory microecosystems with several trophic structure If evolutionary changes or transfer from one steady state to another in the result of changing qualitative properties of the system take place in such systems the main characteristics of these evolution steps can be measured By now this has not been realized from the point of view of methodology though a lot of data on the work of both types of evolutionary machines has been collected In our experiments with long-term continuous cultivation we used the bacterial strains containing in plasmids the cloned genes of bioluminescence and green fluorescent protein which expression level can be easily changed and controlled In spite of the apparent kinetic diversity of evolutionary transfers in two types of systems the general mechanisms characterizing the increase of used energy flow by populations of primer producent can be revealed at their study According to the energy approach at spontaneous transfer from one steady state to another e g in the process of microevolution competition or selection heat dissipation characterizing the rate of entropy growth should increase rather then decrease or maintain steady as usually believed The results of our observations of experimental evolution require further development of thermodynamic theory of open and closed biological systems and further study of general mechanisms of biological

  19. Modeling biomedical experimental processes with OBI

    PubMed Central

    2010-01-01

    Background Experimental descriptions are typically stored as free text without using standardized terminology, creating challenges in comparison, reproduction and analysis. These difficulties impose limitations on data exchange and information retrieval. Results The Ontology for Biomedical Investigations (OBI), developed as a global, cross-community effort, provides a resource that represents biomedical investigations in an explicit and integrative framework. Here we detail three real-world applications of OBI, provide detailed modeling information and explain how to use OBI. Conclusion We demonstrate how OBI can be applied to different biomedical investigations to both facilitate interpretation of the experimental process and increase the computational processing and integration within the Semantic Web. The logical definitions of the entities involved allow computers to unambiguously understand and integrate different biological experimental processes and their relevant components. Availability OBI is available at http://purl.obolibrary.org/obo/obi/2009-11-02/obi.owl PMID:20626927

  20. Simulations of Porcine Eye Exposure to Primary Blast Insult

    PubMed Central

    Watson, Richard; Gray, Walt; Sponsel, William E.; Lund, Brian J.; Glickman, Randolph D.; Groth, Sylvia L.; Reilly, Matthew A.

    2015-01-01

    Purpose A computational model of the porcine eye was developed to simulate primary blast exposure. This model facilitates understanding of blast-induced injury mechanisms. Methods A computational model of the porcine eye was used to simulate the effects of primary blast loading for comparison with experimental findings from shock tube experiments. The eye model was exposed to overpressure-time histories measured during physical experiments. Deformations and mechanical stresses within various ocular tissues were then examined for correlation with pathological findings in the experiments. Results Stresses and strains experienced in the eye during a primary blast event increase as the severity of the blast exposure increases. Peak stresses in the model occurred in locations in which damage was most often observed in the physical experiments. Conclusions Blast injuries to the anterior chamber may be due to inertial displacement of the lens and ciliary body while posterior damage may arise due to contrecoup interactions of the vitreous and retina. Correlation of modeling predictions with physical experiments lends confidence that the model accurately represents the conditions found in the physical experiments. Translational Relevance This computational model offers insights into the mechanisms of ocular injuries arising due to primary blast and may be used to simulate the effects of new protective eyewear designs. PMID:26336633

  1. A Comparison of a Fully Covered and an Uncovered Segmented Biodegradable Esophageal Stent in a Porcine Model: Preclinical Evaluation of Degradation, Complications, and Tissue Reactions

    PubMed Central

    Feng, Yadong; Jiao, Chunhua; Cao, Yang; Zhao, Ye; Chen, Yanfang; Fang, Lin; Shi, Ruihua

    2016-01-01

    Aims. This study was to compare the degradation, complications, and tissue reactions of two segmented biodegradable esophageal stents in a porcine model. Methods. Uncovered biodegradable segmented stents and fully covered biodegradable segmented stents (FCBDS) were transplanted into the porcine esophagus lumen. Data on biodegradation, complications, and tissue reactions were collected and compared. Results. All animals kept good general conditions. No severe complications and stents migration occurred. Stents degradation commenced at week 3. Compared with uncovered stents, stents structure breakage and complete stents absorption in FCBDS were postponed for 1-2 weeks. Hyperplasia was prominent at early stage and ameliorated at late stage after stents insertion. Tissue reactions in FCBDS were milder than those in uncovered stents in the early stage. A longer degradation period was present in FCBDS than in uncovered stents, while FCBDS induced tissue reaction at late stage was mild. Conclusions. Biodegradable esophageal stents with a segmented trunk may be further evaluated in refractory benign esophagus strictures. This FCBDS may be advantageous compared with uncovered stents for a longer degradation period. PMID:27022391

  2. Interactive real-time mapping and catheter ablation of the cavotricuspid isthmus guided by magnetic resonance imaging in a porcine model

    PubMed Central

    Hoffmann, Boris A.; Koops, Andreas; Rostock, Thomas; Müllerleile, Kai; Steven, Daniel; Karst, Roman; Steinke, Mark U.; Drewitz, Imke; Lund, Gunnar; Koops, Susan; Adam, Gerhard; Willems, Stephan

    2010-01-01

    Aims We investigated the feasibility of real-time magnetic resonance imaging (RTMRI) guided ablation of the cavotricuspid isthmus (CTI) by using a MRI-compatible ablation catheter. Methods and results Cavotricuspid isthmus ablation was performed in an interventional RTMRI suite by using a novel 7 French, steerable, non-ferromagnetic ablation catheter in a porcine in vivo model (n = 20). The catheter was introduced and navigated by RTMRI visualization only. Catheter position and movement during manipulation were continuously visualized during the entire intervention. Two porcine prematurely died due to VT/VF. Anatomical completion of the CTI ablation line could be achieved after a mean of 6.3±3 RF pulses (RF energy: 1807±1016.4 Ws/RF pulse, temperature: 55.9±5.9°C) in n = 18 animals. In 15 of 18 procedures (83.3%) a complete CTI block was proven by conventional mapping in the electrophysiological (EP) lab. Conclusion Completely non-fluoroscopic ablation guided by RTMRI using a steerable and non-ferromagnetic catheter is a promising novel technology in interventional electrophysiology. PMID:19897495

  3. Experimental Animal Models in Periodontology: A Review

    PubMed Central

    Struillou, Xavier; Boutigny, Hervé; Soueidan, Assem; Layrolle, Pierre

    2010-01-01

    In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and primates have been used for modeling human periodontal diseases and treatments. However, both the anatomy and physiopathology of animals are different from those of humans, making difficult the evaluation of new therapies. Experimental models have been developed in order to reproduce major periodontal diseases (gingivitis, periodontitis), their pathogenesis and to investigate new surgical techniques. The aim of this review is to define the most pertinent animal models for periodontal research depending on the hypothesis and expected results. PMID:20556202

  4. [Experimental model of ocular ischemic diseases].

    PubMed

    Kiseleva, T N; Chudin, A V

    2014-01-01

    The review presents the most common methods of modeling of retinal ischemia in vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo (a model with increased intraocular pressure, cerebral artery occlusion, chronic ligation of the carotid arteries, photocoagulation of the retinal vessels, occlusion of the central retinal artery, endothelin-1 administration). Modeling ischemic injury in rats is the most frequently used method in studies, because the blood supply of their eyes is similar to blood flow in the human eyes. Each method has its own advantages and disadvantages. Application of methods depends on the purpose of the experimental study. Currently model of ocular ischemic disease can be obtained easily by injecting vasoconstrictive drug endothelin-1. It is the most widely used method of high intraocular pressure induced ocular ischemic damage similar to glaucoma, occlusion of central retinal artery or ophthalmic artery in human. The development of experimental models of ocular ischemic diseases and detailed investigation of mechanisms of impairment of microcirculation are useful for improve the efficiency of diagnostic and treatment of ischemic diseases of retina and optic nerve. PMID:25971134

  5. Experimental models of repetitive brain injuries.

    PubMed

    Weber, John T

    2007-01-01

    Repetitive traumatic brain injury (TBI) occurs in a significant portion of trauma patients, especially in specific populations, such as child abuse victims or athletes involved in contact sports (e.g. boxing, football, hockey, and soccer). A continually emerging hypothesis is that repeated mild injuries may cause cumulative damage to the brain, resulting in long-term cognitive dysfunction. The growing attention to this hypothesis is reflected in several recent experimental studies of repeated mild TBI in vivo. These reports generally demonstrate cellular and cognitive dysfunction after repetitive injury using rodent TBI models. In some cases, data suggests that the effects of a second mild TBI may be synergistic, rather than additive. In addition, some studies have found increases in cellular markers associated with Alzheimer's disease after repeated mild injuries, which demonstrates a direct experimental link between repetitive TBI and neurodegenerative disease. To complement the findings from humans and in vivo experimentation, my laboratory group has investigated the effects of repeated trauma in cultured brain cells using a model of stretch-induced mechanical injury in vitro. In these studies, hippocampal cells exhibited cumulative damage when mild stretch injuries were repeated at either 1-h or 24-h intervals. Interestingly, the extent of damage to the cells was dependent on the time between repeated injuries. Also, a very low level of stretch, which produced no cell damage on its own, induced cell damage when it was repeated several times at a short interval (every 2 min). Although direct comparisons to the clinical situation are difficult, these types of repetitive, low-level, mechanical stresses may be similar to the insults received by certain athletes, such as boxers, or hockey and soccer players. This type of in vitro model could provide a reliable system in which to study the mechanisms underlying cellular dysfunction following repeated injuries. As

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

    PubMed Central

    2014-01-01

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

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

    SciTech Connect

    Davis, Catherine C.; Baccam, Mekhine; Mantz, Mary J.; Osborn, Thomas W.; Hill, Donna R.; Squier, Christopher A.

    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.

  8. Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model

    PubMed Central

    Gu, Wei; Zhang, Qian; Li, Chun-Sheng

    2016-01-01

    Background: Postresuscitation immune dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The purpose of this study was to investigate whether splenic regulatory T-cell (Treg) apoptosis was involved in the postresuscitation immune dysfunction. Methods: Thirty-eight pigs were randomly divided into sham-operated group (SHAM group, n = 8), 12 h post return of spontaneous circulation (ROSC) group, 24 h post-ROSC group, and 48 h post-ROSC group (n = 10 per group). A Wuzhishan miniature porcine model of 8-min ventricular fibrillation cardiac arrest (CA) was established. The apoptosis rates of Treg in the spleen were tested by flow cytometry; the expressions of forkhead/winged helix transcription factor (Foxp3) of Treg in the spleen were detected by real-time polymerase chain reaction; and the levels of interleukin-4 (IL-4), IL-10, and interferon gamma (IFN-γ) of Treg in the spleen were detected by enzyme-linked immunosorbent assay. Results: The apoptosis rates of Treg in all post-ROSC groups were significantly lower than that of SHAM group (7.7% ± 1.9%, 7.1% ± 1.8%, 6.2% ± 0.4% vs. 13.1% ± 1.6%; P < 0.05); the expression levels of Foxp3 and IL-10 were also decreased with the increase of apoptosis rates of Treg. Helper T-cells CD4+ lymphocyte subsets were significantly lower in the post-ROSC groups compared with SHAM group (29.1% ± 2.2%, 24.3% ± 2.2%, 24.1% ± 2.5% vs. 43.8% ± 4.5%; P < 0.01) at 12, 24, and 48 h after ROSC. Compared with SHAM group, the levels of IFN-γ (161.0 ± 12.9, 167.7 ± 10.5, 191.2 ± 7.7 vs. 7.6 ± 0.9 ng/L) and IL-4 (27.7 ± 6.2, 35.9 ± 3.5, 50.6 ± 6.1 vs. 13.3 ± 2.3 ng/L) and the ratio of IFN-γ/IL-4 (8.6 ± 2.3, 4.9 ± 0.4, 4.5 ± 0.9 vs. 0.8 ± 0.2) were all greatly elevated in all post-ROSC groups (P < 0.05). Conclusions: Apoptosis rate of Treg was significantly decreased after CA, and thus the proportion of Treg was increased and the inhibitory effects were

  9. Lentiviral Vector Gene Transfer to Porcine Airways

    PubMed Central

    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). PMID:23187455

  10. Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental Mycobacterium Ulcerans Pig Infection Model

    PubMed Central

    Bolz, Miriam; Ruggli, Nicolas; Borel, Nicole; Pluschke, Gerd; Ruf, Marie-Thérèse

    2016-01-01

    Background Buruli ulcer is a neglected tropical disease of the skin that is caused by infection with Mycobacterium ulcerans. We recently established an experimental pig (Sus scrofa) infection model for Buruli ulcer to investigate host-pathogen interactions, the efficacy of candidate vaccines and of new treatment options. Methodology/Principal Findings Here we have used the model to study pathogenesis and early host-pathogen interactions in the affected porcine skin upon infection with mycolactone-producing and non-producing M. ulcerans strains. Histopathological analyses of nodular lesions in the porcine skin revealed that six weeks after infection with wild-type M. ulcerans bacteria extracellular acid fast bacilli were surrounded by distinct layers of neutrophils, macrophages and lymphocytes. Upon ulceration, the necrotic tissue containing the major bacterial burden was sloughing off, leading to the loss of most of the mycobacteria. Compared to wild-type M. ulcerans bacteria, toxin-deficient mutants caused an increased granulomatous cellular infiltration without massive tissue necrosis, and only smaller clusters of acid fast bacilli. Conclusions/Significance In summary, the present study shows that the pathogenesis and early immune response to M. ulcerans infection in the pig is very well reflecting BU disease in humans, making the pig infection model an excellent tool for the profiling of new therapeutic and prophylactic interventions. PMID:27128097

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

    PubMed Central

    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

  12. Porcine small intestinal epithelial cell line (IPEC-J2) of rotavirus infection as a new model for the study of innate immune responses to rotaviruses and probiotics.

    PubMed

    Liu, Fangning; Li, Guohua; Wen, Ke; Bui, Tammy; Cao, Dianjun; Zhang, Yanming; Yuan, Lijuan

    2010-04-01

    Previous studies of epithelial immune responses to rotavirus infection have been conducted in transformed cell lines. In this study, we evaluated a non-transformed porcine jejunum epithelial cell line (IPEC-J2) as an in-vitro model of rotavirus infection and probiotic treatment. Cell-culture-adapted porcine rotavirus (PRV) OSU strain, or human rotavirus (HRV) Wa strain, along with Lactobacillus acidophilus (LA) or Lactobacillus rhamnosus GG (LGG) were used to inoculate IPEC-J2 cells. LA or LGG treatment was applied pre- or post-rotavirus infection. We demonstrated that IPEC-J2 cells were productively infected by PRV. LA or LGG treatment of the cells did not reduce virus replication. PRV infection increased MUC3 mucin secretion. LGG treatment post-rotavirus infection reduced the mucin secretion response induced by PRV; LGG alone increased the production of membrane-associated MUC3 mucin. LA treatment prior to rotavirus infection significantly increased PRV replication and the IL-6 response to PRV infection, which is consistent with the adjuvant effect of LA. LGG treatment post-rotavirus infection downregulated the IL-6 response, confirming the anti-inflammatory effect of LGG. IPEC-J2 cells expressed toll-like receptor (TLR) 2, TLR3, and TLR9 constitutively. TLR2 expression was upregulated by LGG and peptidoglycan, corresponding to the decreased IL-6 response, indicating that the protective effect of LGG is associated with upregulation of TLR2 expression on intestinal epithelial cells. The IPEC-J2 cell model of PRV infection is a completely homologous system. It is a valuable model for studying the interactions among rotavirus-host-probiotics, and the mechanisms behind the immunomodulating effect of probiotic bacteria on innate immune responses.

  13. Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome

    PubMed Central

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [15O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting 68Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([68Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [68Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [68Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [68Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion. PMID:27069763

  14. Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome.

    PubMed

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion. PMID:27069763

  15. The topical administration of rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) improves healing in a porcine full-thickness excisional wound model.

    PubMed

    Gainza, Garazi; Bonafonte, Diego Celdran; Moreno, Beatriz; Aguirre, José Javier; Gutierrez, Francisco Borja; Villullas, Silvia; Pedraz, José Luis; Igartua, Manoli; Hernandez, Rosa Maria

    2015-01-10

    The development of an effective treatment able to reduce the healing time of chronic wounds is a major health care need. In this regard, our research group has recently demonstrated the in vivo effectiveness of the topical administration of rhEGF-loaded lipid nanoparticles in healing-impaired db/db mice. Here we report the effectiveness of rhEGF-NLC (rhEGF loaded nanostructured lipid carriers) in a more relevant preclinical model of wound healing, the porcine full-thickness excisional wound model. The rhEGF-NLC showed a particle size of around 335nm, negative surface charge (-27mV) and a high encapsulation efficiency of 94%. rhEGF plasma levels were almost undetectable, suggesting that no systemic absorption occurred, which may minimise potential side effects and improve treatment safety. In vivo healing experiments carried out in large white pigs demonstrated that 20μg of rhEGF-NLC topically administered twice a week increased the wound closure and percentage of healed wounds by day 25, compared with the same number of intralesional administrations of 75μg free rhEGF and empty NLC. Moreover, rhEGF-NLC improved the wound healing quality expressed in terms of number of arranged microvasculature, fibroblast migration and proliferation, collagen deposition and evolution of the inflammatory response. Overall, these findings demonstrated that topically administered rhEGF-NLC may generate de novo intact skin after full thickness injury in a porcine model, thereby confirming their potential clinical application for the treatment of chronic wounds.

  16. Isolation, Culture and Identification of Porcine Skeletal Muscle Satellite Cells.

    PubMed

    Li, Bo-Jiang; Li, Ping-Hua; Huang, Rui-Hua; Sun, Wen-Xing; Wang, Han; Li, Qi-Fa; Chen, Jie; Wu, Wang-Jun; Liu, Hong-Lin

    2015-08-01

    The objective of this study was to establish the optimum protocol for the isolation and culture of porcine muscle satellite cells. Mononuclear muscle satellite cells are a kind of adult stem cell, which is located between the basal lamina and sarcolemma of muscle fibers and is the primary source of myogenic precursor cells in postnatal muscle. Muscle satellite cells are a useful model to investigate the mechanisms of muscle growth and development. Although the isolation and culture protocols of muscle satellite cells in some species (e.g. mouse) have been established successfully, the culture system for porcine muscle satellite cells is very limited. In this study, we optimized the isolation procedure of porcine muscle satellite cells and elaborated the isolation and culture process in detail. Furthermore, we characterized the porcine muscle satellite cells using the immunofluorecence. Our study provides a reference for the isolation of porcine muscle satellite cells and will be useful for studying the molecular mechanisms in these cells.

  17. Revelation of the IFNα, IL-10, IL-8 and IL-1β as promising biomarkers reflecting immuno-pathological mechanisms in porcine Huntington's disease model.

    PubMed

    Valekova, Ivona; Jarkovska, Karla; Kotrcova, Eva; Bucci, John; Ellederova, Zdenka; Juhas, Stefan; Motlik, Jan; Gadher, Suresh Jivan; Kovarova, Hana

    2016-04-15

    Studies on Huntington's disease (HD) demonstrated altered immune response in HD gene carriers. Using multiplexing immunoassay, we simultaneously investigated seven cytokines in secretomes of microglia and blood monocytes, cerebrospinal fluid (CSF) and serum collected from transgenic HD minipigs at pre-symptomatic disease stage. Decline in IFNα and IL-10 was observed in CSF and secretome of microglia whilst elevated IL-8 and IL-1β levels were secreted by microglia. Additionally, IL-8 was increased in serum. The proportion of mutant huntingtin in microglia may have causative impact on cytokine production. IFNα, IL-10, IL-8 and IL-1β represent promising biomarkers reflecting immuno-pathological mechanisms in porcine HD model. PMID:27049565

  18. Graphical Models for Quasi-Experimental Designs

    ERIC Educational Resources Information Center

    Kim, Yongnam; Steiner, Peter M.; Hall, Courtney E.; Su, Dan

    2016-01-01

    Experimental and quasi-experimental designs play a central role in estimating cause-effect relationships in education, psychology, and many other fields of the social and behavioral sciences. This paper presents and discusses the causal graphs of experimental and quasi-experimental designs. For quasi-experimental designs the authors demonstrate…

  19. 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

    PubMed Central

    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 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 = 0.20Hz, magnitude >13mm). Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96Hz, magnitude <1mm). The fusion modeling quantified the deleterious effects of respiratory motions on the size and homogeneity of a standard “cigar-shaped” millimetric lesion usually predicted after a 5-second single spherical HIFU exposure in stationary tissues (Dice Similarity Coefficient: DSC<45%). This method assessed the ability to enlarge HIFU ablations during respiration, either by juxtaposing “cigar-shaped” lesions with spherical HIFU exposures, or by generating one large single lesion with toroidal HIFU exposures (DSC>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

  20. Environmental hypothermia in porcine polytrauma and hemorrhagic shock is safe.

    PubMed

    Iyegha, Uroghupatei P; Greenberg, Joseph J; Mulier, Kristine E; Chipman, Jeffrey; George, Mark; Beilman, Greg J

    2012-10-01

    We have previously demonstrated survival benefit to induced hypothermia in a porcine model of controlled hemorrhagic shock simulating an associated delay to definitive care. In the current study, we wished to evaluate the effects of environmental hypothermia in a porcine model of hemorrhagic shock with the addition of polytrauma. Sixteen pigs were randomized to normothermic (39°C, n = 7) or hypothermic (34°C, n = 9) groups. The model included instrumentation, chest injury (captive bolt device), hemorrhage to systolic blood pressure (SBP) of ∼50 mmHg, and crush liver injury. Animals received limited fluid resuscitation for a 1-h period with goal SBP of greater than 80 mmHg and ice packs or warming blankets to achieve goal temperatures, followed by full resuscitation with goal SBP of greater than 90 mmHg, adequate urine output, and hemoglobin by protocol for 20 h. Survivors were observed for an additional 24 h with end points including mortality, markers of organ injury, and neurologic function. There were no differences in survival between the groups (mortality = 1/9, hypothermia group vs. 2/7, normothermia group, P = 0.39). Markers of organ injury were elevated in the hypothermia group at 24 h after injury but were identical between groups at the end of the experimental protocol (48 h after injury). There were no noted differences in neurologic function between the two groups. Environmental hypothermia in a model of polytrauma and hemorrhagic shock was not associated with worse outcomes. PMID:22777118

  1. Infection dynamics and clinical manifestations following experimental inoculation of gilts at 90 days of gestation with a low dose of porcine reproductive and respiratory syndrome virus

    PubMed Central

    Cano, Jean Paul; Dee, Scott A.; Murtaugh, Michael P.; Rovira, Albert; Morrison, Robert B.

    2009-01-01

    Understanding the dynamics of porcine reproductive and respiratory syndrome virus (PRRSV) vertical transmission is important to enhance the accuracy of monitoring protocols for endemically infected breeding herds. The objectives of this study were to determine the prevalence of PRRSV within infected litters, to quantify viremia, and to identify specific attributes of infected individuals. Eight gilts were intramuscularly inoculated with 101 TCID50 of a mildly virulent PRRSV strain (MN-30100) at 90 d of gestation. All inoculated gilts transmitted the virus in utero. The proportion of PRRSV PCR-positive piglets and the level of viremia in the piglets were higher at 4 d of age than at birth or at weaning. No specific attributes were associated with PRRSV infection in the piglets. This is the first report, that we are aware of, documenting the efficient in utero transmission of an extremely low dose of a mildly virulent strain of PRRSV. The results support the sampling of piglets late during lactation as a tool to monitor PRRSV shedding from sow-herds. PMID:20046633

  2. The effects of acid and alkaline solutions on cut marks and on the structure of bone: An experimental study on porcine ribs.

    PubMed

    Amadasi, Alberto; Camici, Arianna; Sironi, Luca; Profumo, Antonella; Merli, Davide; Mazzarelli, Debora; Porta, Davide; Duday, Henri; Cattaneo, Cristina

    2015-11-01

    Among taphonomical modifications during decomposition processes, little is known about the action of high or low pH to human tissues and bones. Moreover, acid or basic solutions are seldom used to ease decomposition and wrecking of the body. In this study a total of 60 samples of porcine bones on which two cut marks were produced before the beginning of the experiment, were put in six different solutions with different pH (1, 3, 5, 9, 12, 14) and analyzed every five days over a period of 70 days. Surveys were carried out macroscopically, with stereomicroscopy and with light microscopy on thin sections. Only the specimens exposed to extremely acid (<1) or basic (>12) pH showed evident modifications of the bone's structure, as witnessed by the analyses with stereomicroscopy as well. Many samples showed a detachment of the periosteum; cut marks became soon unrecognizable with pH 14 but still detectable in all the other samples. The information gained from the present study can be of great help in detecting the exposure of human tissues to high or low environmental pH and in understanding the effects that these solutions can exert on human bones. PMID:26593998

  3. The effects of acid and alkaline solutions on cut marks and on the structure of bone: An experimental study on porcine ribs.

    PubMed

    Amadasi, Alberto; Camici, Arianna; Sironi, Luca; Profumo, Antonella; Merli, Davide; Mazzarelli, Debora; Porta, Davide; Duday, Henri; Cattaneo, Cristina

    2015-11-01

    Among taphonomical modifications during decomposition processes, little is known about the action of high or low pH to human tissues and bones. Moreover, acid or basic solutions are seldom used to ease decomposition and wrecking of the body. In this study a total of 60 samples of porcine bones on which two cut marks were produced before the beginning of the experiment, were put in six different solutions with different pH (1, 3, 5, 9, 12, 14) and analyzed every five days over a period of 70 days. Surveys were carried out macroscopically, with stereomicroscopy and with light microscopy on thin sections. Only the specimens exposed to extremely acid (<1) or basic (>12) pH showed evident modifications of the bone's structure, as witnessed by the analyses with stereomicroscopy as well. Many samples showed a detachment of the periosteum; cut marks became soon unrecognizable with pH 14 but still detectable in all the other samples. The information gained from the present study can be of great help in detecting the exposure of human tissues to high or low environmental pH and in understanding the effects that these solutions can exert on human bones.

  4. Biodegradable elastic patch plasty ameliorates left ventricular adverse remodeling after ischemia–reperfusion injury: A preclinical study of a porous polyurethane material in a porcine model

    PubMed Central

    Hashizume, Ryotaro; Fujimoto, Kazuro L.; Hong, Yi; Guan, Jianjun; Toma, Catalin; Tobita, Kimimasa; Wagner, William R.

    2013-01-01

    Objective Myocardial infarction (MI) can lead to irreversible adverse left ventricular remodeling resulting in subsequent severe dysfunction. The objective of this study was to investigate the potential for biodegradable, elastomeric patch implantation to positively alter the remodeling process after MI in a porcine model. Methods Yorkshire pigs underwent a 60-minute catheter balloon occlusion of the left circumflex artery. Two weeks after MI animals underwent epicardial placement of a biodegradable, porous polyurethane (poly(ester urethane)urea; PEUU) patch (MI+PEUU, n = 7) or sham surgery (MI+sham, n = 8). Echocardiography before surgery and at 4 and 8 weeks after surgery measured the end-diastolic area (EDA) and fractional area change (% FAC). All animals were humanely killed 8 weeks after surgery and hearts were histologically assessed. Results At 8 weeks, echocardiography revealed greater EDA values in the MI+sham group (23.6 ± 6.6 cm2 , mean ± standard deviaation) than in the MI+PEUU group (15.9 ± 2.5 cm2) (P < .05) and a lower %FAC in the MI+sham group (24.8 ± 7.6) than in the MI+PEUU group (35.9 ± 7.8) (P < .05). The infarcted ventricular wall was thicker in the MI+PEUU group (1.56 ± 0.5 cm) than in the MI+sham group (0.91 ± 0.24 cm) (P < .01). Conclusions Biodegradable elastomeric PEUU patch implantation onto the porcine heart 2 weeks post-MI attenuated left ventricular adverse remodeling and functional deterioration and was accompanied by increased neovascularization. These findings, although limited to a 2-month follow-up, may suggest an attractive clinical option to moderate post-MI cardiac failure. PMID:23219497

  5. Corneal-Protective Effects of an Artificial Tear Containing Sodium Hyaluronate and Castor Oil on a Porcine Short-Term Dry Eye Model

    PubMed Central

    HASEGAWA, Takashi; AMAKO, Hideki; YAMAMOTO, Takeshi; TAZAWA, Mariko; SAKAMOTO, Yuji

    2014-01-01

    ABSTRACT The corneal-protective effects of an artificial tear containing sodium hyaluronate (SH) and castor oil (CO) were evaluated on a porcine short-term dry eye model. Fresh porcine eyes with an intact cornea were treated with an artificial tear of saline, SH solution (0.1%, 0.5% or 1%), CO solution (0.5%, 1% or 5%) or a mixture solution containing 0.5% SH and 1% CO and then desiccated for 60, 90 or 180 min. To assess corneal damage, the eyes were stained with methylene blue (MB) or lissamine green (LG). The staining score of MB, absorbance of MB extracted from the cornea and staining density of LG increased significantly with increasing desiccation time in untreated and all artificial tear-treated eyes, although there were no significant differences in staining scores and absorbance of MB between eyes treated continuously with saline and 1% SH-treated ones at 60 and 90 min of desiccation or the mixture-treated eyes at 60 min of desiccation. No significant differences in the staining density of LG were also found between continuous saline-treated eyes and ones desiccated for 60 min and treated with 1% SH and the mixture. Mild cytoplasmic vacuolations were histopathologically observed in the basal and wing cells in eyes desiccated for 60 min and treated with 1% SH and the mixture. The mixture solution containing 0.5% SH and 1% CO has protective effects against corneal desiccation similar to those of 1% SH and would be helpful as an artificial tear. PMID:24881653

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2014-12-18

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

  8. Colonic perianastomotic carcinogenesis in an experimental model

    PubMed Central

    Pérez-Holanda, Sergio; Rodrigo, Luis; Pinyol-Felis, Carme; Vinyas-Salas, Joan

    2008-01-01

    Background To examine the effect of anastomosis on experimental carcinogenesis in the colon of rats. Methods Forty-three 10-week-old male and female Sprague-Dawley rats were operated on by performing an end-to-side ileorectostomy. Group A:16 rats received no treatment. Group B: 27 rats received 18 subcutaneous injections weekly at a dose of 21 mg/kg wt of 1–2 dimethylhydrazine (DMH), from the eighth day after the intervention. Animals were sacrificed between 25–27 weeks. The number of tumours, their localization, size and microscopic characteristics were recorded. A paired chi-squared analysis was performed comparing tumoral induction in the perianastomotic zone with the rest of colon with faeces. Results No tumours appeared in the dimethylhydrazine-free group. The percentage tumoral area was greater in the perianastomotic zone compared to tumours which had developed in the rest of colon with faeces (p = 0.014). Conclusion We found a cocarcinogenic effect due to the creation of an anastomosis, when using an experimental model of colonic carcinogenesis induced by DMH in rats. PMID:18667092

  9. Physicochemical Selectivity of the BBB Microenvironment Governing Passive Diffusion—Matching with a Porcine Brain Lipid Extract Artificial Membrane Permeability Model

    PubMed Central

    Tsinman, Oksana; Tsinman, Konstantin; Sun, Na; Avdeef, Alex

    2011-01-01

    Purpose To mimic the physicochemical selectivity of the blood-brain barrier (BBB) and to predict its passive permeability using a PAMPA model based on porcine brain lipid extract (PBLE 10%w/v in alkane). Methods Three PAMPA (BD pre-coated and PBLE with 2 different lipid volumes) models were tested with 108 drugs. Abraham solvation descriptors were used to interpret the in vitro-in vivo correlation with 282 in situ brain perfusion measurements, spanning over 5 orders of magnitude. An in combo PAMPA model was developed from combining measured PAMPA permeability with one H-bond descriptor. Results The in combo PAMPA predicted 93% of the variance of 197 largely efflux-inhibited insitu permeability training set. The model was cross-validated by the “leave-many-out” procedure, with q2=0.92±0.03. The PAMPA models indicated the presence of paramembrane water channels. Only the PBLE-based PAMPA-BBB model with sufficient lipid to fill all the internal pore space of the filter showed a wide dynamic range window, selectivity coefficient near 1, and was suitable for predicting BBB permeability. Conclusion BBB permeability can be predicted by in combo PAMPA. Its speed and substantially lower cost, compared to in vivo measurements, make it an attractive first-pass screening method for BBB passive permeability. PMID:20945153

  10. Influence of maternal antibodies on efficacy of porcine circovirus type 2 (PCV2) vaccination to protect pigs from experimental infection with PCV2.

    PubMed

    Opriessnig, T; Patterson, A R; Elsener, J; Meng, X J; Halbur, P G

    2008-03-01

    Due to the ubiquitous nature of porcine circovirus type 2 (PCV2) in the pig population and the increasing use of PCV2 vaccines in breeding herds, the majority of dams have been exposed to field PCV2 or PCV2 vaccines, resulting in piglets with varied levels of passively acquired PCV2 maternal antibodies. The objective of the current research was to investigate the influence of passively acquired anti-PCV2 antibodies on PCV2 vaccine efficacy. Sixty 26-day-old pigs were divided into four groups: vaccinated pigs with no maternal PCV2 antibodies at the time of vaccination (VAC-NEG; n = 9), vaccinated pigs with maternal PCV2 antibodies at the time of vaccination (VAC-POS; n = 21), nonvaccinated pigs with no maternal antibodies at the time of challenge (NVAC-CNEG; n = 15), and nonvaccinated pigs with maternal antibodies at the time of challenge (NVAC-CPOS; n = 15). Vaccinations and challenges were performed on trial days 0 and 28, respectively, according to group designation. The pigs were monitored for clinical signs of disease daily and weighed weekly, and blood was collected weekly. All pigs were necropsied on trial day 49, and tissues were evaluated for macroscopic and microscopic lesions. Serum was evaluated using PCV2 immunoglobulin G (IgG) and PCV2 IgM enzyme-linked immunosorbent assays, quantitative PCV2 PCR, and a serum PCV2 neutralizing antibody test. In comparison to NVAC-CPOS pigs, VAC-POS animals had significantly (P < 0.01) less severe microscopic PCV2-associated lymphoid lesions and significantly (P < 0.04) reduced PCV2 genomic copies in serum following PCV2 challenge. These results indicate that vaccination with Suvaxyn PCV2 One Dose reduces viremia and prevents microscopic lesions associated with PCV2 in the presence of maternal antibodies.

  11. Influence of Maternal Antibodies on Efficacy of Porcine Circovirus Type 2 (PCV2) Vaccination To Protect Pigs from Experimental Infection with PCV2▿

    PubMed Central

    Opriessnig, T.; Patterson, A. R.; Elsener, J.; Meng, X. J.; Halbur, P. G.

    2008-01-01

    Due to the ubiquitous nature of porcine circovirus type 2 (PCV2) in the pig population and the increasing use of PCV2 vaccines in breeding herds, the majority of dams have been exposed to field PCV2 or PCV2 vaccines, resulting in piglets with varied levels of passively acquired PCV2 maternal antibodies. The objective of the current research was to investigate the influence of passively acquired anti-PCV2 antibodies on PCV2 vaccine efficacy. Sixty 26-day-old pigs were divided into four groups: vaccinated pigs with no maternal PCV2 antibodies at the time of vaccination (VAC-NEG; n = 9), vaccinated pigs with maternal PCV2 antibodies at the time of vaccination (VAC-POS; n = 21), nonvaccinated pigs with no maternal antibodies at the time of challenge (NVAC-CNEG; n = 15), and nonvaccinated pigs with maternal antibodies at the time of challenge (NVAC-CPOS; n = 15). Vaccinations and challenges were performed on trial days 0 and 28, respectively, according to group designation. The pigs were monitored for clinical signs of disease daily and weighed weekly, and blood was collected weekly. All pigs were necropsied on trial day 49, and tissues were evaluated for macroscopic and microscopic lesions. Serum was evaluated using PCV2 immunoglobulin G (IgG) and PCV2 IgM enzyme-linked immunosorbent assays, quantitative PCV2 PCR, and a serum PCV2 neutralizing antibody test. In comparison to NVAC-CPOS pigs, VAC-POS animals had significantly (P < 0.01) less severe microscopic PCV2-associated lymphoid lesions and significantly (P < 0.04) reduced PCV2 genomic copies in serum following PCV2 challenge. These results indicate that vaccination with Suvaxyn PCV2 One Dose reduces viremia and prevents microscopic lesions associated with PCV2 in the presence of maternal antibodies. PMID:18094109

  12. A prediction model for ocular damage - Experimental validation.

    PubMed

    Heussner, Nico; Vagos, Márcia; Spitzer, Martin S; Stork, Wilhelm

    2015-08-01

    With the increasing number of laser applications in medicine and technology, accidental as well as intentional exposure of the human eye to laser sources has become a major concern. Therefore, a prediction model for ocular damage (PMOD) is presented within this work and validated for long-term exposure. This model is a combination of a raytracing model with a thermodynamical model of the human and an application which determines the thermal damage by the implementation of the Arrhenius integral. The model is based on our earlier work and is here validated against temperature measurements taken with porcine eye samples. For this validation, three different powers were used: 50mW, 100mW and 200mW with a spot size of 1.9mm. Also, the measurements were taken with two different sensing systems, an infrared camera and a fibre optic probe placed within the tissue. The temperatures were measured up to 60s and then compared against simulations. The measured temperatures were found to be in good agreement with the values predicted by the PMOD-model. To our best knowledge, this is the first model which is validated for both short-term and long-term irradiations in terms of temperature and thus demonstrates that temperatures can be accurately predicted within the thermal damage regime. PMID:26267496

  13. Effects of anethole in nociception experimental models.

    PubMed

    Ritter, Alessandra Mileni Versuti; Ames, Franciele Queiroz; Otani, Fernando; de Oliveira, Rubia Maria Weffort; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2014-01-01

    This study investigated the antinociceptive activity of anethole (anethole 1-methoxy-4-benzene (1-propenyl)), major compound of the essential oil of star anise (Illicium verum), in different experimental models of nociception. The animals were pretreated with anethole (62.5, 125, 250, and 500 mg/kg) one hour before the experiments. To eliminate a possible sedative effect of anethole, the open field test was conducted. Anethole (62.5, 125, 250, and 500 mg/kg) showed an antinociceptive effect in the writhing model induced by acetic acid, in the second phase of the formalin test (125 and 250 mg/kg) in the test of glutamate (62.5, 125, and 250 mg/kg), and expresses pain induced by ACF (250 mg/kg). In contrast, anethole was not able to increase the latency time on the hot plate and decrease the number of flinches during the initial phase of the formalin test in any of the doses tested. It was also demonstrated that anethole has no association with sedative effects. Therefore, these data showed that anethole, at all used doses, has no sedative effect and has an antinociceptive effect. This effect may be due to a decrease in the production/release of inflammatory mediators. PMID:25506382

  14. Effects of Anethole in Nociception Experimental Models

    PubMed Central

    Ritter, Alessandra Mileni Versuti; Ames, Franciele Queiroz; Otani, Fernando; de Oliveira, Rubia Maria Weffort; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2014-01-01

    This study investigated the antinociceptive activity of anethole (anethole 1-methoxy-4-benzene (1-propenyl)), major compound of the essential oil of star anise (Illicium verum), in different experimental models of nociception. The animals were pretreated with anethole (62.5, 125, 250, and 500 mg/kg) one hour before the experiments. To eliminate a possible sedative effect of anethole, the open field test was conducted. Anethole (62.5, 125, 250, and 500 mg/kg) showed an antinociceptive effect in the writhing model induced by acetic acid, in the second phase of the formalin test (125 and 250 mg/kg) in the test of glutamate (62.5, 125, and 250 mg/kg), and expresses pain induced by ACF (250 mg/kg). In contrast, anethole was not able to increase the latency time on the hot plate and decrease the number of flinches during the initial phase of the formalin test in any of the doses tested. It was also demonstrated that anethole has no association with sedative effects. Therefore, these data showed that anethole, at all used doses, has no sedative effect and has an antinociceptive effect. This effect may be due to a decrease in the production/release of inflammatory mediators. PMID:25506382

  15. Interactions of porcine circovirus 2 with its hosts.

    PubMed

    Ren, Linzhu; Chen, Xinrong; Ouyang, Hongsheng

    2016-08-01

    Porcine circovirus 2 (PCV2) can cause porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are widely presented in swine-producing countries. Since the discovery of this virus, considerable efforts have been devoted to understanding this pathogen and its interactions with its host. Here, we review the current state of knowledge on interactions between host cell factors and PCV2 with respect to viral proliferation, virus-induced cell apoptosis and autophagy, and host antiviral defenses during PCV2 infection. We also review mouse model systems for PCV2 infection. PMID:27016220

  16. Uniaxial and biaxial mechanical properties of porcine linea alba.

    PubMed

    Cooney, Gerard M; Moerman, Kevin M; Takaza, Michael; Winter, Des C; Simms, Ciaran K

    2015-01-01

    Incisional hernia is a severe complication post-laparoscopic/laparotomy surgery that is commonly associated with the linea alba. However, the few studies on the mechanical properties of the linea alba in the literature appear contradictory, possible due to challenges with the physical dimensions of samples and variations in protocol. This study focuses on the tensile mechanical characterisation of the porcine linea alba, as determined by uniaxial and equi-load biaxial testing using image-based strain measurement methods. Results show that the linea alba demonstrated a non-linear elastic, anisotropic behaviour which is often observed in biological soft tissues. The transverse direction (parallel to fibres) was found to be approximately eight times stiffer than the longitudinal (cross-fibre) direction under both uniaxial and equi-load biaxial loading. The equi-load biaxial tensile tests revealed that contraction could occur in the transverse direction despite increasing load, probably due to the anisotropy of the tissue. Optical surface marker tracking and digital image correlation methods were found to greatly improve the accuracy of stretch measurement, resulting in a 75% change in the apparent stiffness compared to using strain derived from machine cross-head displacement. Additionally, a finite element model of the experiments using a combination of an Ogden and fibre exponential power law model for the linea alba was implemented to quantify the effect of clamping and tissue dimensions (which are suboptimal for tensile testing) on the results. The preliminary model results were used to apply a correction factor to the uniaxial experimental data prior to inverse optimisation to derive best fit material parameters for the fibre reinforced Ogden model. Application of the model to the equi-load biaxial case showed some differences compared to the experimental data, suggesting a more complex anisotropic model may be necessary to capture biaxial behaviour. These

  17. A Porcine Animal Model for Early Meniscal Degeneration – Analysis of Histology, Gene Expression and Magnetic Resonance Imaging Six Months after Resection of the Anterior Cruciate Ligament

    PubMed Central

    Kreinest, Michael; Reisig, Gregor; Ströbel, Philipp; Dinter, Dietmar; Attenberger, Ulrike; Lipp, Peter; Schwarz, Markus

    2016-01-01

    Background/Objective The menisci of the mammalian knee joint balance the incongruence between femoral condyle and tibial plateau and thus menisci absorb and distribute high loads. Degeneration processes of the menisci lead to pain syndromes in the knee joint. The origin of such degenerative processes on meniscal tissue is rarely understood and may be described best as an imbalance of anabolic and catabolic metabolism. A standardized animal model of meniscal degeneration is needed for further studies. The aim of the current study was to develop a porcine animal model with early meniscal degeneration. Material and Methods Resection of the anterior cruciate ligament (ACLR) was performed on the left knee joints of eight Göttingen minipigs. A sham operation was carried out on the right knee joint. The grade of degeneration was determined 26 weeks after the operation using histology and magnetic resonance imaging (MRI). Furthermore, the expression of 14 genes which code for extracellular matrix proteins, catabolic matrix metalloproteinases and inflammation mediators were analyzed. Results Degenerative changes were detected by a histological analysis of the medial meniscus after ACLR. These changes were not detected by MRI. In terms of their gene expression profile, these degenerated medial menisci showed a significantly increased expression of COL1A1. Conclusion This paper describes a new animal model for early secondary meniscal degeneration in the Göttingen minipig. Histopathological evidence of the degenerative changes could be described. This early degenerative changes could not be seen by NMR imaging. PMID:27434644

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

    PubMed

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

    2015-11-12

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

  19. Experimental, Numerical and Observational Models in Geodynamics

    NASA Astrophysics Data System (ADS)

    Lithgow-Bertelloni, Carolina

    2015-04-01

    Geodynamics, the study of the forces that drives all Earth's processes is a rich field that deeply connects all aspects of geological and geophysical studies, from surface observations of the sedimentary record to knowledge of deep Earth structure from mineral physics and seismology. In the context of the solid Earth geodynamics primarily focuses on lithosphere and mantle dynamics, while core dynamics is the purview of geomagnetism. I will focus this talk on the former, its historical context and future developments. We have known the equations of motion and mechanics for ~200 years, but only relatively recently can they be solved with enough accuracy and resolution to do geology. We have made great strides since Arthur Holmes conceptual models of mantle flow, thanks to computational and experimental advances. We can know model plate boundaries globally with resolutions in the order of a few kms and image temperature and velocity simultaneously in the laboratory in 3D and non-intrusively. We have also learned a great deal about the physics of the Earth, from composition to rheology. New theories on plate boundary rheology are paving the way for self-consistent generation of plates from mantle flow. New computational methods allow for adaptive meshing, fabric development and history, so we can study deformation and compare directly to geological observations in mountain ranges and continental rifts. We can use ever more sophisticated images of mantle structure from seismic and other geophysical data to probe the relationship between melting, flow and dynamical processes. We can reconstruct landscapes and relief, plate motions and sedimentation and ask how much the mantle has contributed to drainage reversal, sedimentation and climate change. The future of the field is ever brighter.

  20. A human experimental model of episodic pain.

    PubMed

    Petrini, Laura; Hennings, Kristian; Li, Xi; Negro, Francesco; Arendt-Nielsen, Lars

    2014-12-01

    An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants were subjected to 45 min of intense painful cutaneous electrical stimulation (episodic pain session), using a stimulus paradigm that in animals has been shown to induce long-term potentiation. These electrical stimulations produced a verbal pain rating of approximately 85 on a 0-100 verbal rating scale (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused significantly increased cutaneous blood flow around the site of the stimulation. Axon flare reflex and blood flow reached a plateau on day one in all the subjects and no significant changes between the days were observed. The results showed that the effect of the electrical stimulations changed over the five days; pain potentiation was induced on the first day (significant increase in the verbal pain ratings during the 45 min stimulation) but not on any of the subsequent days. After five days of subsequent pain induction, the global field power showed a significant reduction in P2 amplitude in the late stage (200-370 ms, in the central-parietal area). In conclusion, the results suggest that in healthy individuals this model of episodic pain produces a rapid adaptation after day one and that generates significant SEP changes at day five.

  1. Splicing variants of porcine synphilin-1.

    PubMed

    Larsen, Knud; Madsen, Lone Bruhn; Farajzadeh, Leila; Bendixen, Christian

    2015-09-01

    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. PMID:26101749

  2. Experimental modelling of outburst flood - bed interactions

    NASA Astrophysics Data System (ADS)

    Carrivick, J. L.; Xie, Z.; Sleigh, A.; Hubbard, M.

    2009-04-01

    Outburst floods are a sudden release and advancing wave of water and sediment, with a peak discharge that is often several orders of magnitude greater than perennial flows. Common outburst floods from natural sources include those from glacial and moraine-impounded lakes, freshwater dyke and levee bursts, volcanic debris dams, landslides, avalanches, coastal bay-bars, and those from tree or vegetation dams. Outburst flood hazards are regularly incorporated into risk assessments for urban, coastal and mountainous areas, for example. Outburst flood hazards are primarily due to direct impacts, caused by a frontal surge wave, from debris within a flow body, and from the mass and consistency of the flows. A number of secondary impacts also pose hazards, including widespread deposition of sediment and blocked tributary streams. It is rapid landscape change, which is achieved the mobilization and redistribution of sediment that causes one of the greatest hazards due to outburst floods. The aim of this project is therefore to parameterise hydrodynamic - sedimentary interactions in experimental outburst floods. Specifically, this project applies laboratory flume modelling, which offers a hitherto untapped opportunity for examining complex interactions between water and sediment within outburst floods. The experimental set-up is of a tradition lock-gate design with a straight 4 m long tank. Hydraulics are scaled at 1:20 froude scale and the following controls on frontal wave flow-bed interactions and hence on rapid landscape change are being investigated: 1. Pre-existing mobile sediment effects, fixed bed roughness effects, sediment concentration effects, mobile bed effects. An emphasis is being maintained on examining the downstream temporal and spatial change in physical character of the water / sediment frontal wave. Facilities are state-of-the-art with a fully-automated laser bed-profiler to measure bed elevation after a run, Seatek arrays to measure transient flow

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

    PubMed

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

    2012-02-01

    Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n = 6) or normothermia (38°C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P < 0.05) and miR-208b (P < 0.05), respectively. Therapeutic hypothermia significantly diminished the increase in miR-122 compared with the normothermic group (P < 0.005). In our model, hypothermia was initiated after coronary reperfusion and did not affect either myocardial damage as previously assessed by magnetic resonance imaging or the plasma level of miR-208b. Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.

  4. Novel Glucagon-Like Peptide-1 Analog Delivered Orally Reduces Postprandial Glucose Excursions in Porcine and Canine Models

    PubMed Central

    Eldor, Roy; Kidron, Miriam; Greenberg-Shushlav, Yael; Arbit, Ehud

    2010-01-01

    Background Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence. Methods Healthy, fasting, enterically cannulated pigs and beagle canines were administered a single dose of the exenatide-based ORMD-0901 formulation 30 min before oral glucose challenges. Blood samples were collected every 15 min for evaluation of ORMD-0901 safety and efficacy in regulating postchallenge glucose excursions. Results Enterically delivered ORMD-0901 was well tolerated by all animals. ORMD-0901 formulations RG3 and AG2 led to reduced glucose excursions in pigs when delivered prior to a 5 g/kg glucose challenge, where area under the curve (AUC)0–120 values were up to 43% lower than in control sessions. All canines challenged with a glucose load with no prior exposure to exenatide, demonstrated higher AUC0–150 values than in their exenatide-treated sessions. Subcutaneous exenatide delivery amounted to a 51% reduction in mean glucose AUC0–150, while formulations AG4 and AG3 prompted 43% and 29% reductions, respectively. Conclusions When delivered enterically, GLP-1 (ORMD-0901) is absorbed from the canine and porcine gastrointestinal tracts and retains its biological activity. Further development of this drug class in an oral dosage form is expected to enhance diabetes control and patient compliance. PMID:21129350

  5. Trolox and ascorbic acid reduce direct and indirect oxidative stress in the IPEC-J2 cells, an in vitro model for the porcine gastrointestinal tract.

    PubMed

    Vergauwen, Hans; Tambuyzer, Bart; Jennes, Karen; Degroote, Jeroen; Wang, Wei; De Smet, Stefaan; Michiels, Joris; Van Ginneken, Chris

    2015-01-01

    Oxidative stress in the small intestinal epithelium is a major cause of barrier malfunction and failure to regenerate. This study presents a functional in vitro model using the porcine small intestinal epithelial cell line IPEC-J2 to examine the effects of oxidative stress and to estimate the antioxidant and regenerative potential of Trolox, ascorbic acid and glutathione monoethyl ester. Hydrogen peroxide and diethyl maleate affected the tight junction (zona occludens-1) distribution, significantly increased intracellular oxidative stress (CM-H2DCFDA) and decreased the monolayer integrity (transepithelial electrical resistance and FD-4 permeability), viability (neutral red) and wound healing capacity (scratch assay). Trolox (2 mM) and 1 mM ascorbic acid pre-treatment significantly reduced intracellular oxidative stress, increased wound healing capacity and reduced FD-4 permeability in oxidatively stressed IPEC-J2 cell monolayers. All antioxidant pre-treatments increased transepithelial electrical resistance and viability only in diethyl maleate-treated cells. Glutathione monoethyl ester (10 mM) pre-treatment significantly decreased intracellular oxidative stress and monolayer permeability only in diethyl maleate-treated cells. These data demonstrate that the IPEC-J2 oxidative stress model is a valuable tool to screen antioxidants before validation in piglets. PMID:25745867

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

    PubMed

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

    2000-01-01

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

  7. Palindrome regeneration by template strand-switching mechanism at the origin of DNA replication of porcine circovirus via the rolling-circle melting-pot replication model.

    PubMed

    Cheung, Andrew K

    2004-09-01

    Palindromic sequences (inverted repeats) flanking the origin of DNA replication with the potential of forming single-stranded stem-loop cruciform structures have been reported to be essential for replication of the circular genomes of many prokaryotic and eukaryotic systems. In this study, mutant genomes of porcine circovirus with deletions in the origin-flanking palindrome and incapable of forming any cruciform structures invariably yielded progeny viruses containing longer and more stable palindromes. These results suggest that origin-flanking palindromes are essential for termination but not for initiation of DNA replication. Detection of template strand switching in the middle of an inverted repeat strand among the progeny viruses demonstrated that both the minus genome and a corresponding palindromic strand served as templates simultaneously during DNA biosynthesis and supports the recently proposed rolling-circle "melting-pot" replication model. The genome configuration presented by this model, a four-stranded tertiary structure, provides insights into the mechanisms of DNA replication, inverted repeat correction (or conversion), and illegitimate recombination of any circular DNA molecule with an origin-flanking palindrome.

  8. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome.

    PubMed

    Boker, Abdulaziz; Graham, M Ruth; Walley, Keith R; McManus, Bruce M; Girling, Linda G; Walker, Elizabeth; Lefevre, Gerald R; Mutch, W Alan C

    2002-02-15

    We compared biologically variable ventilation (V (bv); n = 9) with control mode ventilation (V (c); n = 8) at low tidal volume (VT)--initial 6 ml/kg--in a porcine model of acute respiratory distress syndrome (ARDS). Hemodynamics, respiratory gases, airway pressures, and VT data were measured. Static P-V curves were generated at 5 h. Interleukin (IL)-8 and IL-10 were measured in serum and tracheal aspirate. By 5 h, higher Pa(O(2)) (173 +/- 30 mm Hg versus 119 +/- 23 mm Hg; mean +/- SD; p < 0.0001 group x time interaction [G x T]), lower shunt fraction (6 +/- 1% versus 9 +/- 3%; p = 0.0026, G x T) at lower peak airway pressure (21 +/- 2 versus 24 +/- 1 cm H(2)O; p = 0.0342; G x T) occurred with V (bv). IL-8 concentrations in tracheal aspirate and wet:dry weight ratios were inversely related; p = 0.011. With V (c), IL-8 concentrations were 3.75-fold greater at wet:dry weight ratio of 10. IL-10 concentrations did not differ between groups. In both groups, ventilation was on the linear portion of the P-V curve. With V (bv), VT variability demonstrated an inverse power law indicating fractal behavior. In this model of ARDS, V (bv) improved Pa(O(2)) at lower peak airway pressure and IL-8 levels compared with V (c).

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

    PubMed

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

    2014-08-01

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

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

    PubMed

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

    2010-01-01

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

  11. Xenotransplantation and porcine cytomegalovirus.

    PubMed

    Denner, Joachim

    2015-01-01

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

  12. Biomass thermochemical gasification: Experimental studies and modeling

    NASA Astrophysics Data System (ADS)

    Kumar, Ajay

    The overall goals of this research were to study the biomass thermochemical gasification using experimental and modeling techniques, and to evaluate the cost of industrial gas production and combined heat and power generation. This dissertation includes an extensive review of progresses in biomass thermochemical gasification. Product gases from biomass gasification can be converted to biopower, biofuels and chemicals. However, for its viable commercial applications, the study summarizes the technical challenges in the gasification and downstream processing of product gas. Corn stover and dried distillers grains with solubles (DDGS), a non-fermentable byproduct of ethanol production, were used as the biomass feedstocks. One of the objectives was to determine selected physical and chemical properties of corn stover related to thermochemical conversion. The parameters of the reaction kinetics for weight loss were obtained. The next objective was to investigate the effects of temperature, steam to biomass ratio and equivalence ratio on gas composition and efficiencies. DDGS gasification was performed on a lab-scale fluidized-bed gasifier with steam and air as fluidizing and oxidizing agents. Increasing the temperature resulted in increases in hydrogen and methane contents and efficiencies. A model was developed to simulate the performance of a lab-scale gasifier using Aspen Plus(TM) software. Mass balance, energy balance and minimization of Gibbs free energy were applied for the gasification to determine the product gas composition. The final objective was to optimize the process by maximizing the net energy efficiency, and to estimate the cost of industrial gas, and combined heat and power (CHP) at a biomass feedrate of 2000 kg/h. The selling price of gas was estimated to be 11.49/GJ for corn stover, and 13.08/GJ for DDGS. For CHP generation, the electrical and net efficiencies were 37 and 86%, respectively for corn stover, and 34 and 78%, respectively for DDGS. For

  13. Development of a network based model to simulate the between-farm transmission of the porcine reproductive and respiratory syndrome virus.

    PubMed

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

    2015-11-18

    Contact structure within a population can significantly affect the outcomes of infectious disease spread models. The objective of this study was to develop a network based simulation model for the between-farm spread of porcine reproductive and respiratory syndrome virus to assess the impact of contact structure on between-farm transmission of PRRS virus. For these farm level models, a hypothetical population of 500 swine farms following a multistage production system was used. The contact rates between farms were based on a study analyzing movement of pigs in Canada, while disease spread parameters were extracted from published literature. Eighteen distinct scenarios were designed and simulated by varying the mode of transmission (direct versus direct and indirect contact), type of index herd (farrowing, nursery and finishing), and the presumed network structures among swine farms (random, scale-free and small-world). PRRS virus was seeded in a randomly selected farm and 500 iterations of each scenario were simulated for 52 weeks. The median epidemic size by the end of the simulated period and percentage die-out for each scenario, were the key outcomes captured. Scenarios with scale-free network models resulted in the largest epidemic sizes, while scenarios with random and small-world network models resulted in smaller and similar epidemic sizes. Similarly, stochastic die-out percentage was least for scenarios with scale-free networks followed by random and small-world networks. Findings of the study indicated that incorporating network structures among the swine farms had a considerable impact on the spread of PRRS virus, highlighting the importance of understanding and incorporating realistic contact structures when developing infectious disease spread models for similar populations.

  14. Ultrafast laser machining of porcine sclera

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    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 demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  16. The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

    PubMed

    Chung, Wen Yuan; Gravante, Gianpiero; Al-Leswas, Dhya; Arshad, Ali; Sorge, Roberto; Watson, Chris C; Pollard, Cristina; Metcalfe, Matthew S; Dennison, Ashley R

    2013-05-01

    We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments. PMID:23489088

  17. Functional Genomics Unique to Week 20 Post Wounding in the Deep Cone/Fat Dome of the Duroc/Yorkshire Porcine Model of Fibroproliferative Scarring

    PubMed Central

    Engrav, Loren H.; Tuggle, Christopher K.; Kerr, Kathleen F.; Zhu, Kathy Q.; Numhom, Surawej; Couture, Oliver P.; Beyer, Richard P.; Hocking, Anne M.; Carrougher, Gretchen J.; Ramos, Maria Luiza C.; Klein, Matthew B.; Gibran, Nicole S.

    2011-01-01

    Background Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete. Methodology/Principal Findings We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. Conclusions/Significance 1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring. PMID:21533106

  18. Experimentally Induced Mammalian Models of Glaucoma

    PubMed Central

    Yoshitomi, Takeshi; Zorumski, Charles F.; Izumi, Yukitoshi

    2015-01-01

    A wide variety of animal models have been used to study glaucoma. Although these models provide valuable information about the disease, there is still no ideal model for studying glaucoma due to its complex pathogenesis. Animal models for glaucoma are pivotal for clarifying glaucoma etiology and for developing novel therapeutic strategies to halt disease progression. In this review paper, we summarize some of the major findings obtained in various glaucoma models and examine the strengths and limitations of these models. PMID:26064891

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

    PubMed

    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.

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

    PubMed Central

    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

    abstract 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

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

    PubMed

    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

  2. The effect of long-term amiodarone administration on myocardial fibrosis and evolution of left ventricular remodeling in a porcine model of ischemic cardiomyopathy.

    PubMed

    Zagorianou, Anastasia; Marougkas, Meletios; Drakos, Stavros G; Diakos, Nikolaos; Konstantopoulos, Panagiotis; Perrea, Despina N; Anastasiou-Nana, Maria; Malliaras, Konstantinos

    2016-01-01

    Amiodarone is effective in suppressing arrhythmias in heart failure patients. We investigated the effect of long-term amiodarone administration on myocardial fibrosis and left ventricular (LV) remodeling in a porcine model of ischemic cardiomyopathy. Eighteen infarcted farm pigs were randomized to receive long-term amiodarone administration for 3 months (n = 9) or conventional follow-up (n = 9). Evolution of LV remodeling over 3 months post-myocardial infarction was examined at tissue level (myocyte size, myocardial fibrosis and vascular density assessed by whole-field digital histopathology), organ level (LV structure and function assessed by echocardiography), and systemic level (BNP and MMP-9 levels). Long-term administration of the standard anti-arrhythmic doses of amiodarone was not associated with adverse effects on myocardial fibrosis and other features of adverse cardiac remodeling. This favorable safety profile suggests that long-term anti-arrhythmic therapy with amiodarone warrants further clinical investigation in the subpopulation of heart failure patients with significantly increased burden of arrhythmias. PMID:27652141

  3. Combined experimental/analytical modeling using component mode synthesis

    SciTech Connect

    Martinez, D.R.; Carne, T.G.; Gregory, D.L.; Miller, A.K.

    1984-01-01

    This study evaluates the accuracy of computed model frequencies and mode shapes obtained from a combined experimental/analytical model for a simple beam structure. The structure was divided into two subsystems, and one subsystem was tested to obtain its free-free modes. Using a Component Mode Synthesis (CMS) technique, the experimental model data base for one subsystem was directly coupled with a finite element model of the other subsystem to create an experimental/analytical model of the total structure. Both the translational and rotational elements of the residual flexibilities and mode shapes at the interface of the experimental subsystem were measured and used in the coupling. The modal frequencies and mode shapes obtained for the combined experimental/analytical model are compared to those for a reference finite element model of the entire structure. The sensitivity of the CMS model predictions to errors in the modal parameters and residual flexibilities, which are required to define a subsystem, is also examined.

  4. A mathematical model for analyzing the elasticity, viscosity, and failure of soft tissue: comparison of native and decellularized porcine cardiac extracellular matrix for tissue engineering.

    PubMed

    Bronshtein, Tomer; Au-Yeung, Gigi Chi Ting; Sarig, Udi; Nguyen, Evelyne Bao-Vi; Mhaisalkar, Priyadarshini S; Boey, Freddy Yin Chiang; Venkatraman, Subbu S; Machluf, Marcelle

    2013-08-01

    The clinical success of tissue-engineered constructs commonly requires mechanical properties that closely mimic those of the human tissue. Determining the viscoelastic properties of such biomaterials and the factors governing their failure profiles, however, has proven challenging, although collecting extensive data regarding their tensile behavior is straightforward. The easily calculated Young's modulus remains the most reported mechanical measure, regardless of its limitations, even though single-relaxation-time (SRT) models can provide much more information, which remain scarce due to a lack of manageable tools for implementing these models. We developed an easy-to-use algorithm for applying the Zener SRT model and determining the elastic moduli, viscosity, and failure profiles of materials under different mechanical tests in a user-independent manner. The algorithm was validated on the data resulting from tensile tests on native and decellularized porcine cardiac tissue, previously suggested as a promising scaffold material for cardiac tissue engineering. This analysis yields new and more accurate measurements such as the elastic moduli and viscosity, the model's relaxation time, and information on the factors governing the materials' failure profiles. These measurements indicate that the viscoelasticity and strength of the decellularized acellular extracellular matrix (ECM) are similar to those of native tissue, although its elasticity and apparent viscosity are higher. Nonetheless, reseeding and culturing the ECM with mesenchymal stem cells was shown to partially restore the mechanical properties lost after decellularization. We propose this algorithm as a platform for soft-tissue analysis that can provide comparable and unbiased measures for characterizing viscoelastic biomaterials commonly used in tissue engineering.

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

    PubMed

    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

  6. Susceptibility of porcine preimplantation embryos to viruses associated with reproductive failure.

    PubMed

    Zhao, Haijing; Zhao, Guangyuan; Wang, Wenjun

    2016-10-15

    In the modern biological area, the applications of pig as a laboratory model have extensive prospects, such as gene transfer, IVF, SCNT, and xenotransplantation. However, the risk of pathogen transmission by porcine embryos is always a topic to be investigated, especially the viruses related to reproductive failure, for instance, pseudorabies virus, porcine reproductive and respiratory syndrome virus, porcine parvovirus, and porcine circovirus type 2. It should be mentioned that the zona pellucida (ZP) of porcine embryos can be a barrier against the viruses, but certain pathogens may stick to or even pass through the ZP. With intact, free, and damaged ZP, porcine preimplantation embryos are susceptible to these viruses in varying degrees, which may be associated with the virus-specific receptor on embryonic cell membrane. These topics are discussed in the present review. PMID:27423729

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

    PubMed

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

    2011-01-01

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

  8. A High Protein Diet during Pregnancy Affects Hepatic Gene Expression of Energy Sensing Pathways along Ontogenesis in a Porcine Model

    PubMed Central

    Oster, Michael; Murani, Eduard; Metges, Cornelia C.; Ponsuksili, Siriluck; Wimmers, Klaus

    2011-01-01

    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. PMID:21789176

  9. Modeling and experimental investigating loop heat pipes

    SciTech Connect

    Kiseev, V.M.; Pogorelov, N.P.; Nouroutdinov, V.A.

    1995-12-31

    Design variants of two-phase systems of thermal control with heat flux inversion and experimental data are presented. Simplified functional dependence of heat flux for loop heat pipes with heat flux inversion versus effective pore radius of capillary structures under various external conditions are obtained.

  10. Local delivery of allogeneic bone marrow and adipose tissue-derived mesenchymal stromal cells for cutaneous wound healing in a porcine model.

    PubMed

    Hanson, Summer E; Kleinbeck, Kyle R; Cantu, David; Kim, Jaeyhup; Bentz, Michael L; Faucher, Lee D; Kao, W John; Hematti, Peiman

    2016-02-01

    Wound healing remains a major challenge in modern medicine. Bone marrow- (BM) and adipose tissue- (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT-MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM- or AT-MSCs were administered intradermally (1 x 10(6) cells) into partial-thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC-injected wounds were associated with improved appearance and faster re-epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM- and AT-MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM- and AT-MSC for treatment of cutaneous wounds through modulation of healing and epithelialization.

  11. Combined experimental/analytical modeling using component mode synthesis

    SciTech Connect

    Martinez, D.R.; Carne, T.G.; Gregory, D.L.; Miller, A.K.

    1984-04-01

    This study evaluates the accuracy of computed modal frequencies and mode shapes obtained from a combined experimental/analytical model for a simple beam structure. The structure was divided into two subsystems and one subsystem was tested to obtain its free-free modes. Using a Component Mode Synthesis (CMS) technique, the experimental modal data base for one subsystem was directly coupled with a finite element model of the other subsystem to create an experimental/analytical model of the total structure. Both the translational and rotational elements of the residual flexibilities and mode shapes at the interface of the experimental subsystem were measured and used in the coupling. The modal frequencies and mode shapes obtained for the combined experimental/analytical model are compared to those for a reference finite element model of the entire structure. The sensitivity of the CMS model predictions to errors in the modal parameters and residual flexibilities, which are required to define a subsystem, is also examined.

  12. Heart Rate Variability in Porcine Progressive Peritonitis-Induced Sepsis

    PubMed Central

    Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Sviglerova, Jitka; Florova, Blanka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

    2016-01-01

    Accumulating evidence suggests that heart rate variability (HRV) alterations could serve as an indicator of sepsis progression and outcome, however, the relationships of HRV and major pathophysiological processes of sepsis remain unclear. Therefore, in this experimental study HRV was investigated in a clinically relevant long-term porcine model of severe sepsis/septic shock. HRV was analyzed by several methods and the parameters were correlated with pathophysiological processes of sepsis. In 16 anesthetized, mechanically ventilated, and instrumented domestic pigs of either gender, sepsis was induced by fecal peritonitis. Experimental subjects were screened up to the refractory shock development or death. ECG was continuously recorded throughout the experiment, afterwards RR intervals were detected and HRV parameters computed automatically using custom made measurement and analysis MATLAB routines. In all septic animals, progressive hyperdynamic septic shock developed. The statistical measures of HRV, geometrical measures of HRV and Poincaré plot analysis revealed a pronounced reduction of HRV that developed quickly upon the onset of sepsis and was maintained throughout the experiment. The frequency domain analysis demonstrated a decrease in the high frequency component and increase in the low frequency component together with an increase of the low/high frequency component ratio. The reduction of HRV parameters preceded sepsis-associated hemodynamic changes including heart rate increase or shock progression. In a clinically relevant porcine model of peritonitis-induced progressive septic shock, reduction of HRV parameters heralded sepsis development. HRV reduction was associated with a pronounced parasympathetic inhibition and a shift of sympathovagal balance. Early reduction of HRV may serve as a non-invasive and sensitive marker of systemic inflammatory syndrome, thereby widening the therapeutic window for early interventions. PMID:26779039

  13. Experimental Diabetes Mellitus in Different Animal Models.

    PubMed

    Al-Awar, Amin; Kupai, Krisztina; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. PMID:27595114

  14. Experimental Diabetes Mellitus in Different Animal Models

    PubMed Central

    Al-awar, Amin; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

  15. Experimental Diabetes Mellitus in Different Animal Models

    PubMed Central

    Al-awar, Amin; Veszelka, Médea; Szűcs, Gergő; Attieh, Zouhair; Murlasits, Zsolt; Török, Szilvia; Pósa, Anikó; Varga, Csaba

    2016-01-01

    Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. PMID:27595114

  16. Porcine myelomonocytic markers and cell populations.

    PubMed

    Ezquerra, A; Revilla, C; Alvarez, B; Pérez, C; Alonso, F; Domínguez, J

    2009-03-01

    This review focuses in what is currently known about swine myeloid markers, the expression and function of these receptors in the biology of porcine myelomonocytic cells, the regulation of their expression along the different developmental stages of these cells and their utility to investigate the heterogeneity of monocyte and macrophage populations. Although the number of monoclonal antibodies recognizing surface antigens expressed on either swine granulocytes or monocytes is low compared with those available for human or mouse, they have contributed significantly to study the members of myeloid lineages in this species, allowing to discriminate different maturation stages of these cells in bone marrow and to reveal the heterogeneity of blood monocytes and tissue macrophages. Porcine myeloid cells share many similarities with humans, highlighting the relevance of the pig as a biomedical model.

  17. Biomechanical response of the pediatric abdomen, part 1: development of an experimental model and quantification of structural response to dynamic belt loading.

    PubMed

    Kent, Richard; Stacey, Stephen; Kindig, Matthew; Forman, Jason; Woods, William; Rouhana, Stephen W; Higuchi, Kazuo; Tanji, Hiromasa; Lawrence, Schuyler St; Arbogast, Kristy B

    2006-11-01

    The abdomen is the second most commonly injured region in children using adult seat belts, but engineers are limited in their efforts to design systems that mitigate these injuries since no current pediatric dummy has the capability to quantify injury risk from loading to the abdomen. This paper develops a porcine (sus scrofa domestica) model of the 6-year-old human's abdomen, and then defines the biomechanical response of this abdominal model. First, a detailed abdominal necropsy study was undertaken, which involved collecting a series of anthropometric measurements and organ masses on 25 swine, ranging in age from 14 to 429 days (4-101 kg mass). These were then compared to the corresponding human quantities to identify the best porcine representation of a 6-year-old human's abdomen. This was determined to be a pig of age 77 days, and whole-body mass of 21.4 kg. The sub-injury, quasistatic response to belt loading of this porcine model compared well with pediatric human volunteer tests performed with a lap belt on the lower abdomen. A test fixture was designed to produce transverse, dynamic belt loading on the porcine abdomen. A detailed review of field cases identified the following test variables: loading location (upper/lower), penetration magnitude (23%-68% of initial abdominal depth), muscle tensing (yes/no), and belt penetration rate (quasistatic, dynamic 2.9 m/s - 7.8 m/s). Dynamic tests were performed on 47 post-mortem subjects. Belt tension and dorsal reaction force were cross-plotted with abdominal penetration to generate structural response corridors. Subcutaneous stimulation of the anterior abdominal muscle wall stiffened the quasistatic response significantly, but was of negligible importance in the dynamic tests. The upper abdomen exhibited stiffer response quasistatically, and also was more sensitive to penetration rate, with stiffness increasing significantly over the range of dynamic rates tested here. In contrast, the lower abdomen was relatively

  18. Biomechanical response of the pediatric abdomen, part 1: development of an experimental model and quantification of structural response to dynamic belt loading.

    PubMed

    Kent, Richard; Stacey, Stephen; Kindig, Matthew; Forman, Jason; Woods, William; Rouhana, Stephen W; Higuchi, Kazuo; Tanji, Hiromasa; Lawrence, Schuyler St; Arbogast, Kristy B

    2006-11-01

    The abdomen is the second most commonly injured region in children using adult seat belts, but engineers are limited in their efforts to design systems that mitigate these injuries since no current pediatric dummy has the capability to quantify injury risk from loading to the abdomen. This paper develops a porcine (sus scrofa domestica) model of the 6-year-old human's abdomen, and then defines the biomechanical response of this abdominal model. First, a detailed abdominal necropsy study was undertaken, which involved collecting a series of anthropometric measurements and organ masses on 25 swine, ranging in age from 14 to 429 days (4-101 kg mass). These were then compared to the corresponding human quantities to identify the best porcine representation of a 6-year-old human's abdomen. This was determined to be a pig of age 77 days, and whole-body mass of 21.4 kg. The sub-injury, quasistatic response to belt loading of this porcine model compared well with pediatric human volunteer tests performed with a lap belt on the lower abdomen. A test fixture was designed to produce transverse, dynamic belt loading on the porcine abdomen. A detailed review of field cases identified the following test variables: loading location (upper/lower), penetration magnitude (23%-68% of initial abdominal depth), muscle tensing (yes/no), and belt penetration rate (quasistatic, dynamic 2.9 m/s - 7.8 m/s). Dynamic tests were performed on 47 post-mortem subjects. Belt tension and dorsal reaction force were cross-plotted with abdominal penetration to generate structural response corridors. Subcutaneous stimulation of the anterior abdominal muscle wall stiffened the quasistatic response significantly, but was of negligible importance in the dynamic tests. The upper abdomen exhibited stiffer response quasistatically, and also was more sensitive to penetration rate, with stiffness increasing significantly over the range of dynamic rates tested here. In contrast, the lower abdomen was relatively

  19. Cooking Potatoes: Experimentation and Mathematical Modeling.

    ERIC Educational Resources Information Center

    Chen, Xiao Dong

    2002-01-01

    Describes a laboratory activity involving a mathematical model of cooking potatoes that can be solved analytically. Highlights the microstructure aspects of the experiment. Provides the key aspects of the results, detailed background readings, laboratory procedures and data analyses. (MM)

  20. Experimentally validated finite element model of electrocaloric multilayer ceramic structures

    SciTech Connect

    Smith, N. A. S. E-mail: maciej.rokosz@npl.co.uk Correia, T. M. E-mail: maciej.rokosz@npl.co.uk; Rokosz, M. K. E-mail: maciej.rokosz@npl.co.uk

    2014-07-28

    A novel finite element model to simulate the electrocaloric response of a multilayer ceramic capacitor (MLCC) under real environment and operational conditions has been developed. The two-dimensional transient conductive heat transfer model presented includes the electrocaloric effect as a source term, as well as accounting for radiative and convective effects. The model has been validated with experimental data obtained from the direct imaging of MLCC transient temperature variation under application of an electric field. The good agreement between simulated and experimental data, suggests that the novel experimental direct measurement methodology and the finite element model could be used to support the design of optimised electrocaloric units and operating conditions.

  1. Isolation, cloning, and characterization of a novel phosphomannan-binding lectin from porcine serum.

    PubMed

    Ma, Bruce Yong; Nakamura, Natsuko; Dlabac, Vladimir; Naito, Haruna; Yamaguchi, Shinsuke; Ishikawa, Makiko; Nonaka, Motohiro; Ishiguro, Masaji; Kawasaki, Nobuko; Oka, Shogo; Kawasaki, Toshisuke

    2007-04-27

    Mannan-binding protein (MBP) is a C-type serum lectin that is an important constituent of the innate immune defense because it activates the complement system via the lectin pathway. While the pig has been proposed to be an attractive source of xenotransplantable tissues and organs, little is known about porcine MBP. In our previous studies, phosphomannan, but not mannan, was found to be an effective inhibitor of the C1q-independent bactericidal activity of newborn piglet serum against some rough strains of Gram-negative bacteria. In contrast, the inhibitory activities of phosphomannan and mannan were very similar in the case of MBP-dependent bactericidal activity against rough strains of Escherichia coli K-12 and S-16. Based on these findings, we inferred that an MBP-like lectin with slightly or completely different carbohydrate binding specificity might exist in newborn piglet serum and be responsible for the C1q-independent bactericidal activity. Herein we report that a novel phosphomannan-binding lectin (PMBL) of 33 kDa under reducing conditions was isolated from both newborn and adult porcine serum and characterized. Porcine PMBL functionally activated the complement system via the lectin pathway triggered by binding with both phosphomannan (P-mannan) and mannan, which, unlike MBP, was effectively inhibited by mannose 6-phosphate- or galatose-containing oligosaccharides. Our observations suggest that porcine PMBL plays a critical role in the innate immune defense from the newborn stage to adult-hood, and the establishment of a newborn piglet experimental model for the innate immune system studies is a valuable step toward elucidation of the physiological function and molecular mechanism of lectin pathway. PMID:17324926

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

    PubMed

    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

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

    PubMed

    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

  4. Gear Windage Modeling Progress - Experimental Validation Status

    NASA Technical Reports Server (NTRS)

    Kunz, Rob; Handschuh, Robert F.

    2008-01-01

    In the Subsonics Rotary Wing (SRW) Project being funded for propulsion work at NASA Glenn Research Center, performance of the propulsion system is of high importance. In current rotorcraft drive systems many gearing components operate at high rotational speed (pitch line velocity > 24000 ft/ min). In our testing of high speed helical gear trains at NASA Glenn we have found that the work done on the air - oil mist within the gearbox can become a significant part of the power loss of the system. This loss mechanism is referred to as windage. The effort described in this presentation is to try to understand the variables that affect windage, develop a good experimental data base to validate, the analytical project being conducted at Penn State University by Dr. Rob Kunz under a NASA SRW NRA. The presentation provides an update to the status of these efforts.

  5. Import risk assessment incorporating a dose-response model: introduction of highly pathogenic porcine reproductive and respiratory syndrome into Australia via illegally imported raw pork.

    PubMed

    Brookes, V J; Hernández-Jover, M; Holyoake, P; Ward, M P

    2014-03-01

    Highly pathogenic porcine reproductive and respiratory syndrome (PRRS) has spread through parts of south-east Asia, posing a risk to Australia. The objective of this study was to assess the probability of infection of a feral or domestic pig in Australia with highly pathogenic PRRS following ingestion of illegally imported raw pork. A conservative scenario was considered in which 500 g of raw pork was imported from the Philippines into Australia without being detected by border security, then discarded from a household and potentially accessed by a pig. Monte Carlo simulation of a two-dimensional, stochastic model was used to estimate the probability of entry and exposure, and the probability of infection was assessed by incorporating a virus-decay and mechanistic dose-response model. Results indicated that the probability of infection of a feral pig after ingestion of raw meat was higher than the probability of infection of a domestic pig. Sensitivity analysis was used to assess the influence of input parameters on model output probability estimates, and extension of the virus-decay and dose-response model was used to explore the impact of different temperatures and time from slaughter to ingestion of the meat, different weights of meat, and the level of viraemia at slaughter on the infectivity of meat. Parameters with the highest influence on the model output were the level of viraemia of a pig prior to slaughter and the probability of access by a feral pig to food-waste discarded on property surrounding a household. Extension of the decay and dose-response model showed that small pieces of meat (10 g) from a highly pathogenic PRRS viraemic pig could contain enough virus to have a high probability of infection of a pig, and that routes to Australia by sea or air from all highly pathogenic PRRS virus endemic countries were of interest dependent on the temperature of the raw meat during transport. This study highlighted the importance of mitigation strategies such

  6. Modeling Graves' Orbitopathy in Experimental Graves' Disease.

    PubMed

    Banga, J P; Moshkelgosha, S; Berchner-Pfannschmidt, U; Eckstein, A

    2015-09-01

    Graves' orbitopathy (GO), also known as thyroid eye disease is an inflammatory disease of the orbital tissue of the eye that arises as a consequence of autoimmune thyroid disease. The central feature of the disease is the production of antibodies to the thyrotropin hormone receptor (TSHR) that modulate the function of the receptor leading to autoimmune hyperthyroidism and GO. Over the years, all viable preclinical models of Graves' disease have been incomplete and singularly failed to progress in the treatment of orbital complications. A new mouse model of GO based upon immunogenic presentation of human TSHR A-subunit plasmid by close field electroporation is shown to lead to induction of prolonged functional antibodies to TSHR resulting in chronic disease with subsequent progression to GO. The stable preclinical GO model exhibited pathologies reminiscent of human disease characterized by orbital remodeling by inflammation and adipogenesis. Inflammatory lesions characterized by CD3+ T cells and macrophages were localized in the orbital muscle tissue. This was accompanied by extensive adipogenesis of orbital fat in some immune animals. Surprisingly, other signs of orbital involvement were reminiscent of eyelid inflammation involving chemosis, with dilated and congested orbital blood vessels. More recently, the model is replicated in the author's independent laboratories. The pre-clinical model will provide the basis to study the pathogenic and regulatory roles of immune T and B cells and their subpopulations to understand the initiation, pathophysiology, and progression of GO.

  7. Experimental evaluations of the microchannel flow model

    NASA Astrophysics Data System (ADS)

    Parker, K. J.

    2015-06-01

    Recent advances have enabled a new wave of biomechanics measurements, and have renewed interest in selecting appropriate rheological models for soft tissues such as the liver, thyroid, and prostate. The microchannel flow model was recently introduced to describe the linear response of tissue to stimuli such as stress relaxation or shear wave propagation. This model postulates a power law relaxation spectrum that results from a branching distribution of vessels and channels in normal soft tissue such as liver. In this work, the derivation is extended to determine the explicit link between the distribution of vessels and the relaxation spectrum. In addition, liver tissue is modified by temperature or salinity, and the resulting changes in tissue responses (by factors of 1.5 or greater) are reasonably predicted from the microchannel flow model, simply by considering the changes in fluid flow through the modified samples. The 2 and 4 parameter versions of the model are considered, and it is shown that in some cases the maximum time constant (corresponding to the minimum vessel diameters), could be altered in a way that has major impact on the observed tissue response. This could explain why an inflamed region is palpated as a harder bump compared to surrounding normal tissue.

  8. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  9. Experimental Design and Multiplexed Modeling Using Titrimetry and Spreadsheets

    NASA Astrophysics Data System (ADS)

    Harrington, Peter De B.; Kolbrich, Erin; Cline, Jennifer

    2002-07-01

    The topics of experimental design and modeling are important for inclusion in the undergraduate curriculum. Many general chemistry and quantitative analysis courses introduce students to spreadsheet programs, such as MS Excel. Students in the laboratory sections of these courses use titrimetry as a quantitative measurement method. Unfortunately, the only model that students may be exposed to in introductory chemistry courses is the working curve that uses the linear model. A novel experiment based on a multiplex model has been devised for titrating several vinegar samples at a time. The multiplex titration can be applied to many other routine determinations. An experimental design model is fit to titrimetric measurements using the MS Excel LINEST function to estimate concentration from each sample. This experiment provides valuable lessons in error analysis, Class A glassware tolerances, experimental simulation, statistics, modeling, and experimental design.

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

    PubMed Central

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

    2016-01-01

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

  11. Relationship between retrograde coronary blood flow and the extent of no-reflow and infarct size in a porcine ischemia-reperfusion model.

    PubMed

    Stavrakis, Stavros; Terrovitis, John; Tsolakis, Elias; Drakos, Stavros; Dalianis, Argirios; Bonios, Michael; Koudoumas, Dimitrios; Malliaras, Konstantinos; Nanas, John

    2011-02-01

    Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia-reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30 min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2 h of reperfusion predicted a larger IA (r = 0.71; p = 0.001). Time-to-development of retrograde CBF was inversely related to IA (r = -0.55; p = 0.019) and NR (r = -0.62; p = 0.006). A larger IA (OR 1.12, 95% CI 1.01-1.24, p = 0.037) and NR (OR 1.09, 95% CI 1.01-1.18, p = 0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level. PMID:21153063

  12. 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.

    PubMed

    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

  13. Xenotransplantation of Bone Marrow-Derived Human Mesenchymal Stem Cell Sheets Attenuates Left Ventricular Remodeling in a Porcine Ischemic Cardiomyopathy Model

    PubMed Central

    Kawamura, Masashi; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Toda, Koichi; Daimon, Takashi; Shimizu, Tatsuya; Okano, Teruo

    2015-01-01

    Introduction: Bone marrow-derived autologous human mesenchymal stem cells (MSCs) are one of the most promising cell sources for cell therapy to treat heart failure. The cell sheet technique has allowed transplantation of a large number of cells and enhanced the efficacy of cell therapy. We hypothesized that the transplantation of MSC sheets may be a feasible, safe, and effective treatment for ischemic cardiomyopathy (ICM). Methods and Results: Human MSCs acquired from bone marrow were positive for CD73, CD90, and CD105 and negative for CD11b and CD45 by flow cytometry. Ten MSC sheets were created from a total cell number of 1×108 MSCs using temperature-responsive culture dishes. These were successfully transplanted over the infarct myocardium of porcine ICM models induced by placing an ameroid constrictor on the left anterior descending coronary artery without any procedural-related complications (MSC group=6: sheet transplantation; sham group=6, oral intake of tacrolimus in both groups). Premature ventricular contractions were rarely detected by Holter electrocardiogram (ECG) in the MSC group in the first week after transplantation. On echocardiography, the cardiac performance of the MSC group was significantly better than that of the sham group at 8 weeks after transplantation. On histological examination 8 weeks after transplantation, left ventricular (LV) remodeling was significantly attenuated compared with the sham group (cardiomyocyte size and interstitial fibrosis were measured). Immunohistochemistry of the von Willebrand factor showed that the vascular density in the infarct border area was significantly greater in the MSC group than the sham group. Expression of angiogenesis-related factors in the infarct border area of the MSC group was significantly greater than that of the sham group, as measured by real-time polymerase chain reaction. Conclusions: Bone marrow-derived MSC sheets improved cardiac function and attenuated LV remodeling in ICM without

  14. Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a β-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model

    PubMed Central

    Skorup, Paul; Maudsdotter, Lisa; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Jonsson, Ann-Beth; Sjölin, Jan

    2014-01-01

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal’s individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome. PMID:24587365

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

    PubMed Central

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

    2016-01-01

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

  16. A Multimodality Imaging Approach for Serial Assessment of Regional Changes in Lower Extremity Arteriogenesis and Tissue Perfusion in a Porcine Model of Peripheral Arterial Disease

    PubMed Central

    Stacy, Mitchel R.; Yu, Da Yu; Maxfield, Mark W.; Jaba, Irina M.; Jozwik, Bartosz P.; Zhuang, Zhen W.; Lin, Ben A.; Hawley, Christi L.; Caracciolo, Christopher M.; Pal, Prasanta; Tirziu, Daniela; Sampath, Smita; Sinusas, Albert J.

    2014-01-01

    Background A standard quantitative imaging approach to evaluate peripheral arterial disease (PAD) does not exist. Quantitative tools for evaluating arteriogenesis in vivo are not readily available and the feasibility of monitoring serial regional changes in lower extremity perfusion has not been examined. Methods and Results Serial changes in lower extremity arteriogenesis and muscle perfusion were evaluated following femoral artery occlusion in a porcine model using SPECT/CT imaging with post-mortem validation of in vivo findings using gamma counting, post-mortem imaging, and histological analysis. Hybrid thallium-201 (201Tl) SPECT/CT imaging was performed in pigs (n=8) at baseline, immediately post-occlusion, and at 1 and 4 weeks post-occlusion. CT imaging was used to identify muscle regions of interest in the ischemic (I) and non-ischemic (NI) hindlimbs for quantification of regional changes in CT defined arteriogenesis and quantification of 201Tl perfusion. Four weeks post-occlusion, post-mortem tissue 201Tl activity was measured by gamma counting and immunohistochemistry was performed to assess capillary density. Relative 201Tl retention (I/NI) was reduced immediately post-occlusion in distal and proximal muscles and remained lower in calf and gluteus muscles 4 weeks later. Analysis of CT angiography revealed collateralization at 4 weeks within proximal muscles (p<0.05). SPECT perfusion correlated with tissue gamma counting at 4 weeks (p=0.01). Increased capillary density was seen within the ischemic calf at 4 weeks (p=0.004). Conclusions 201Tl SPECT/CT imaging permits serial, regional quantification of arteriogenesis and resting tissue perfusion following limb ischemia. This approach may be effective for detection of disease and monitoring therapy in PAD. PMID:24170237

  17. A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental model.

    PubMed

    Apitz-Castro, R; Badimon, J J; Badimon, L

    1994-08-01

    Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. We used a well characterized perfusion chamber to study the in vivo effects of ajoene on platelet deposition onto a highly thrombogenic, severely damaged arterial wall, obtained by stripping off the intimal layer and exposing tunica media. Platelet-vessel wall interaction and the effect of ajoene was studied under flow conditions of high and low local shear rate that mimics laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at local low blood shear rate. Ajoene does not inhibit binding of vWF to GPIb, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/IIIa, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, under in vivo flow conditions and in the presence of physiological calcium levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, mainly in arterial sites with local low shear rates.

  18. Scaled Experimental Modeling of VHTR Plenum Flows

    SciTech Connect

    ICONE 15

    2007-04-01

    Abstract The Very High Temperature Reactor (VHTR) is the leading candidate for the Next Generation Nuclear Power (NGNP) Project in the U.S. which has the goal of demonstrating the production of emissions free electricity and hydrogen by 2015. Various scaled heated gas and water flow facilities were investigated for modeling VHTR upper and lower plenum flows during the decay heat portion of a pressurized conduction-cooldown scenario and for modeling thermal mixing and stratification (“thermal striping”) in the lower plenum during normal operation. It was concluded, based on phenomena scaling and instrumentation and other practical considerations, that a heated water flow scale model facility is preferable to a heated gas flow facility and to unheated facilities which use fluids with ranges of density to simulate the density effect of heating. For a heated water flow lower plenum model, both the Richardson numbers and Reynolds numbers may be approximately matched for conduction-cooldown natural circulation conditions. Thermal mixing during normal operation may be simulated but at lower, but still fully turbulent, Reynolds numbers than in the prototype. Natural circulation flows in the upper plenum may also be simulated in a separate heated water flow facility that uses the same plumbing as the lower plenum model. However, Reynolds number scaling distortions will occur at matching Richardson numbers due primarily to the necessity of using a reduced number of channels connected to the plenum than in the prototype (which has approximately 11,000 core channels connected to the upper plenum) in an otherwise geometrically scaled model. Experiments conducted in either or both facilities will meet the objectives of providing benchmark data for the validation of codes proposed for NGNP designs and safety studies, as well as providing a better understanding of the complex flow phenomena in the plenums.

  19. Software reliability: Repetitive run experimentation and modeling

    NASA Technical Reports Server (NTRS)

    Nagel, P. M.; Skrivan, J. A.

    1982-01-01

    A software experiment conducted with repetitive run sampling is reported. Independently generated input data was used to verify that interfailure times are very nearly exponentially distributed and to obtain good estimates of the failure rates of individual errors and demonstrate how widely they vary. This fact invalidates many of the popular software reliability models now in use. The log failure rate of interfailure time was nearly linear as a function of the number of errors corrected. A new model of software reliability is proposed that incorporates these observations.

  20. Experimental Control of Simple Pendulum Model

    ERIC Educational Resources Information Center

    Medina, C.

    2004-01-01

    This paper conveys information about a Physics laboratory experiment for students with some theoretical knowledge about oscillatory motion. Students construct a simple pendulum that behaves as an ideal one, and analyze model assumption incidence on its period. The following aspects are quantitatively analyzed: vanishing friction, small amplitude,…

  1. Experimental Investigation of Iron Plasma Opacity Models

    SciTech Connect

    Bailey, J. E.; Rochau, G. A.; Hansen, S. B.; Nash, T. J.; Nielsen, D. S.; Lake, P. W.; Iglesias, C. A.; Mancini, R. C.; MacFarlane, J. J.; Golovkin, I.; Wang, P.; Blancard, C.; Cosse, Ph.; Faussurier, G.; Gilleron, F.; Pain, J. C.; Abdallah, J. Jr.; Pradhan, A. K.; Nahar, S. N.

    2009-09-10

    Recent experiments extended iron opacity model tests to temperatures above 150 eV for the first time. The experiments use the Z Facility to volumetrically heat a CH-tamped Fe/Mg plasma using x-rays. The frequency dependent sample transmission is measured by viewing a backlight through the sample. The plasma conditions are inferred from the Mg K-shell absorption. The strategy for this research is to examine the underlying physics within Fe opacity models by comparisons with the measured transmission. Physics topics of interest include charge state distribution, energy level structure, and line broadening. In this talk we discuss methods to exploit the data and advance understanding for these topics. In addition, we review new experiments under way to further improve the data and to achieve higher energy density conditions.

  2. Performance Modeling of Experimental Laser Lightcrafts

    NASA Technical Reports Server (NTRS)

    Wang, Ten-See; Chen, Yen-Sen; Liu, Jiwen; Myrabo, Leik N.; Mead, Franklin B., Jr.; Turner, Jim (Technical Monitor)

    2001-01-01

    A computational plasma aerodynamics model is developed to study the performance of a laser propelled Lightcraft. The computational methodology is based on a time-accurate, three-dimensional, finite-difference, chemically reacting, unstructured grid, pressure-based formulation. The underlying physics are added and tested systematically using a building-block approach. The physics modeled include non-equilibrium thermodynamics, non-equilibrium air-plasma finite-rate kinetics, specular ray tracing, laser beam energy absorption and refraction by plasma, non-equilibrium plasma radiation, and plasma resonance. A series of transient computations are performed at several laser pulse energy levels and the simulated physics are discussed and compared with those of tests and literatures. The predicted coupling coefficients for the Lightcraft compared reasonably well with those of tests conducted on a pendulum apparatus.

  3. Experimental Forelimb Allotransplantation in Canine Model.

    PubMed

    Hong, Sa-Hyeok; Eun, Seok-Chan

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  4. Experimental Forelimb Allotransplantation in Canine Model

    PubMed Central

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  5. Different experimental approaches in modelling cataractogenesis

    PubMed Central

    Kyselova, Zuzana

    2010-01-01

    Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed. PMID:21217865

  6. Porcine circovirus type 2 detection in in vitro produced porcine blastocysts after virus sperm exposure.

    PubMed

    Galeati, Giovanna; Zannoni, Augusta; Spinaci, Marcella; Bucci, Diego; Ostanello, Fabio; Panarese, Serena; Tamanini, Carlo; Sarli, Giuseppe

    2016-04-01

    This study was aimed at assessing the capability of semen experimentally infected with porcine circovirus type 2 (PCV2) to produce porcine blastocysts PCR positive for PCV2. Embryos were obtained from in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes or by parthenogenesis. Sperm suspension was exposed to PCV2b and utilized for IVF. PCV2 spiked semen did not reveal any reduction in sperm viability or motility but its ability to produce infected blastocysts was irrelevant as only one out of 15 blastocysts obtained by IVF were PCV2b; however two blastocysts were PCV2a positive. Furthermore, the presence of PCV2 was demonstrated also in embryos obtained by parthenogenesis (one out of 17 was PCV2b and one PCV2a positive). Even if PCV2 firmly attaches to the surface of spermatozoa, experimentally spiked sperm were not effective in infecting oocytes during IVF and in producing PCR positive embryos. The infected blastocysts we obtained derived most probably from infected oocytes recovered at the abattoir. PMID:26434667

  7. Experimental models of hepatocellular carcinoma: developments and evolution.

    PubMed

    Wu, Long; Tang, Zhao-You; Li, Yan

    2009-08-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The biological mechanisms of hepatocarcinogenesis and progression are poorly understood. Experimental models of HCC provide valuable tools to evaluate the risk factors, new treatment modalities and biologic characteristics. Under the constant evolution in model design and technology development, new experimental models continue to emerge, including spontaneous models, induced models, viral models, transplantable models, and genetically engineered models. These models are used as tools to investigate basic biological mechanisms of growth and differentiation, oncogene function, and as systems to test new diagnostic and therapeutic approaches. Each model has its own advantages and disadvantages. The progress in HCC model construction and studies are summarized in this review. PMID:19399516

  8. Experimental Validation of a Thermoelastic Model for SMA Hybrid Composites

    NASA Technical Reports Server (NTRS)

    Turner, Travis L.

    2001-01-01

    This study presents results from experimental validation of a recently developed model for predicting the thermomechanical behavior of shape memory alloy hybrid composite (SMAHC) structures, composite structures with an embedded SMA constituent. The model captures the material nonlinearity of the material system with temperature and is capable of modeling constrained, restrained, or free recovery behavior from experimental measurement of fundamental engineering properties. A brief description of the model and analysis procedures is given, followed by an overview of a parallel effort to fabricate and characterize the material system of SMAHC specimens. Static and dynamic experimental configurations for the SMAHC specimens are described and experimental results for thermal post-buckling and random response are presented. Excellent agreement is achieved between the measured and predicted results, fully validating the theoretical model for constrained recovery behavior of SMAHC structures.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. Experimentally testing the standard cosmological model

    SciTech Connect

    Schramm, D.N. Fermi National Accelerator Lab., Batavia, IL )

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, {Omega}{sub b}, remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that {Omega}{sub b} {approximately} 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming {Omega}{sub total} = 1) and the need for dark baryonic matter, since {Omega}{sub visible} < {Omega}{sub b}. Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M{sub x} {approx gt} 20 GeV and an interaction weaker than the Z{sup 0} coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for {nu}-masses may imply that the {nu}{sub {tau}} is a good hot dark matter candidate. 73 refs., 5 figs.

  11. Experimental photoallergic contact dermatitis: a mouse model

    SciTech Connect

    Maguire, H.C. Jr.; Kaidbey, K.

    1982-09-01

    We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model.

  12. Experimental and analytical generic space station dynamic models

    NASA Technical Reports Server (NTRS)

    Belvin, W. K.; Edighoffer, H. H.

    1986-01-01

    A dynamic model used for verification of analytical and experimental methods is documented. The model consists of five substructures to simulate the multibody, low frequency nature of large space structures. Design considerations which led to a fundamental vibration frequency of less than one Hz are described. Finite element analysis used to predict the vibration modes and frequencies of the experimental model is presented. In addition, modeling of cable suspension effects using prestressed vibration analysis is described. Details of the expermental and analytical models are included to permit replication of the study. Results of the modal vibration tests and analysis are presented in a separate document.

  13. Segmented Polynomial Models in Quasi-Experimental Research.

    ERIC Educational Resources Information Center

    Wasik, John L.

    1981-01-01

    The use of segmented polynomial models is explained. Examples of design matrices of dummy variables are given for the least squares analyses of time series and discontinuity quasi-experimental research designs. Linear combinations of dummy variable vectors appear to provide tests of effects in the two quasi-experimental designs. (Author/BW)

  14. Experimental Models on Effects of Psychostimulants.

    PubMed

    Kõks, Sulev

    2015-01-01

    Psychostimulants are a diverse group of substances that cause an increase in psychomotor activity at least in part through their actions on catecholaminergic systems including the dopaminergic mesolimbic pathways. Animal models used to study addiction are based on the psychomotor stimulant theory of addiction. The basics of this theory are that the reinforcing effects and the addition liabilities of the drugs can be predicted from their ability to induce psychomotor activation. This approach focuses on the ability of the drugs to directly control the animal's behavior and to induce psychomotor stimulation, and is consistent with the behavioral definition of addiction and behavioral sensitization. Animal experiments have the advantage over clinical studies of lower variation and fewer confounding effects. PMID:26070755

  15. Experimental Models on Effects of Psychostimulants.

    PubMed

    Kõks, Sulev

    2015-01-01

    Psychostimulants are a diverse group of substances that cause an increase in psychomotor activity at least in part through their actions on catecholaminergic systems including the dopaminergic mesolimbic pathways. Animal models used to study addiction are based on the psychomotor stimulant theory of addiction. The basics of this theory are that the reinforcing effects and the addition liabilities of the drugs can be predicted from their ability to induce psychomotor activation. This approach focuses on the ability of the drugs to directly control the animal's behavior and to induce psychomotor stimulation, and is consistent with the behavioral definition of addiction and behavioral sensitization. Animal experiments have the advantage over clinical studies of lower variation and fewer confounding effects.

  16. Experimental investigation of a flapping wing model

    NASA Astrophysics Data System (ADS)

    Hubel, Tatjana Y.; Tropea, Cameron

    The main objective of this research study was to investigate the aerodynamic forces of an avian flapping wing model system. The model size and the flow conditions were chosen to approximate the flight of a goose. Direct force measurements, using a three-component balance, and PIV flow field measurements parallel and perpendicular to the oncoming flow, were performed in a wind tunnel at Reynolds numbers between 28,000 and 141,000 (3-15 m/s), throughout a range of reduced frequencies between 0.04 and 0.20. The appropriateness of quasi-steady assumptions used to compare 2D, time-averaged particle image velocimetry (PIV) measurements in the wake with direct force measurements was evaluated. The vertical force coefficient for flapping wings was typically significantly higher than the maximum coefficient of the fixed wing, implying the influence of unsteady effects, such as delayed stall, even at low reduced frequencies. This puts the validity of the quasi-steady assumption into question. The (local) change in circulation over the wing beat cycle and the circulation distribution along the wingspan were obtained from the measurements in the tip and transverse vortex planes. Flow separation could be observed in the distribution of the circulation, and while the circulation derived from the wake measurements failed to agree exactly with the absolute value of the circulation, the change in circulation over the wing beat cycle was in excellent agreement for low and moderate reduced frequencies. The comparison between the PIV measurements in the two perpendicular planes and the direct force balance measurements, show that within certain limitations the wake visualization is a powerful tool to gain insight into force generation and the flow behavior on flapping wings over the wing beat cycle.

  17. Experimental investigation of a flapping wing model

    NASA Astrophysics Data System (ADS)

    Hubel, Tatjana Y.; Tropea, Cameron

    2009-05-01

    The main objective of this research study was to investigate the aerodynamic forces of an avian flapping wing model system. The model size and the flow conditions were chosen to approximate the flight of a goose. Direct force measurements, using a three-component balance, and PIV flow field measurements parallel and perpendicular to the oncoming flow, were performed in a wind tunnel at Reynolds numbers between 28,000 and 141,000 (3-15 m/s), throughout a range of reduced frequencies between 0.04 and 0.20. The appropriateness of quasi-steady assumptions used to compare 2D, time-averaged particle image velocimetry (PIV) measurements in the wake with direct force measurements was evaluated. The vertical force coefficient for flapping wings was typically significantly higher than the maximum coefficient of the fixed wing, implying the influence of unsteady effects, such as delayed stall, even at low reduced frequencies. This puts the validity of the quasi-steady assumption into question. The (local) change in circulation over the wing beat cycle and the circulation distribution along the wingspan were obtained from the measurements in the tip and transverse vortex planes. Flow separation could be observed in the distribution of the circulation, and while the circulation derived from the wake measurements failed to agree exactly with the absolute value of the circulation, the change in circulation over the wing beat cycle was in excellent agreement for low and moderate reduced frequencies. The comparison between the PIV measurements in the two perpendicular planes and the direct force balance measurements, show that within certain limitations the wake visualization is a powerful tool to gain insight into force generation and the flow behavior on flapping wings over the wing beat cycle.

  18. Cardiovascular Magnetic Resonance Imaging in Experimental Models

    PubMed Central

    Price, Anthony N.; Cheung, King K.; Cleary, Jon O; Campbell, Adrienne E; Riegler, Johannes; Lythgoe, Mark F

    2010-01-01

    Cardiovascular magnetic resonance (CMR) imaging is the modality of choice for clinical studies of the heart and vasculature, offering detailed images of both structure and function with high temporal resolution. Small animals are increasingly used for genetic and translational research, in conjunction with models of common pathologies such as myocardial infarction. In all cases, effective methods for characterising a wide range of functional and anatomical parameters are crucial for robust studies. CMR is the gold-standard for the non-invasive examination of these models, although physiological differences, such as rapid heart rate, make this a greater challenge than conventional clinical imaging. However, with the help of specialised magnetic resonance (MR) systems, novel gating strategies and optimised pulse sequences, high-quality images can be obtained in these animals despite their small size. In this review, we provide an overview of the principal CMR techniques for small animals for example cine, angiography and perfusion imaging, which can provide measures such as ejection fraction, vessel anatomy and local blood flow, respectively. In combination with MR contrast agents, regional dysfunction in the heart can also be identified and assessed. We also discuss optimal methods for analysing CMR data, particularly the use of semi-automated tools for parameter measurement to reduce analysis time. Finally, we describe current and emerging methods for imaging the developing heart, aiding characterisation of congenital cardiovascular defects. Advanced small animal CMR now offers an unparalleled range of cardiovascular assessments. Employing these methods should allow new insights into the structural, functional and molecular basis of the cardiovascular system. PMID:21331311

  19. Mathematical Models and the Experimental Analysis of Behavior

    ERIC Educational Resources Information Center

    Mazur, James E.

    2006-01-01

    The use of mathematical models in the experimental analysis of behavior has increased over the years, and they offer several advantages. Mathematical models require theorists to be precise and unambiguous, often allowing comparisons of competing theories that sound similar when stated in words. Sometimes different mathematical models may make…

  20. A systematic review of animal models for experimental neuroma.

    PubMed

    Toia, Francesca; Giesen, Thomas; Giovanoli, Pietro; Calcagni, Maurizio

    2015-10-01

    Peripheral neuromas can result in an unbearable neuropathic pain and functional impairment. Their treatment is still challenging, and their optimal management is to be defined. Experimental research still plays a major role, but - although numerous neuroma models have been proposed on different animals - there is still no single model recognised as being the reference. Several models show advantages over the others in specific aspects of neuroma physiopathology, prevention or treatment, making it unlikely that a single model could be of reference. A reproducible and standardised model of peripheral neuroma would allow better comparison of results from different studies. We present a systematic review of the literature on experimental in vivo models, analysing advantages and disadvantages, specific features and indications, with the goal of providing suggestions to help their standardisation. Published models greatly differ in the animal and the nerve employed, the mechanisms of nerve injury and the evaluation methods. Specific experimental models exist for terminal neuromas and neuromas in continuity (NIC). The rat is the most widely employed animal, the rabbit being the second most popular model. NIC models are more actively researched, but it is more difficult to generate such studies in a reproducible manner. Nerve transection is considered the best method to cause terminal neuromas, whereas partial transection is the best method to cause NIC. Traditional histomorphology is the historical gold-standard evaluation method, but immunolabelling, reverse transcriptase-polymerase chain reaction (RT-PCR) and proteomics are gaining increasing popularity. Computerised gait analysis is the gold standard for motor-recovery evaluation, whereas mechanical testing of allodynia and hyperalgesia reproducibly assesses sensory recovery. This review summarises current knowledge on experimental neuroma models, and it provides a useful tool for defining experimental protocols

  1. Development of an Ex Vivo Porcine Lung Model for Studying Growth, Virulence, and Signaling of Pseudomonas aeruginosa

    PubMed Central

    Muruli, Aneesha; Higgins, Steven; Diggle, Stephen P.

    2014-01-01

    Research into chronic infection by bacterial pathogens, such as Pseudomonas aeruginosa, uses various in vitro and live host models. While these have increased our understanding of pathogen growth, virulence, and evolution, each model has certain limitations. In vitro models cannot recapitulate the complex spatial structure of host organs, while experiments on live hosts are limited in terms of sample size and infection duration for ethical reasons; live mammal models also require specialized facilities which are costly to run. To address this, we have developed an ex vivo pig lung (EVPL) model for quantifying Pseudomonas aeruginosa growth, quorum sensing (QS), virulence factor production, and tissue damage in an environment that mimics a chronically infected cystic fibrosis (CF) lung. In a first test of our model, we show that lasR mutants, which do not respond to 3-oxo-C12-homoserine lactone (HSL)-mediated QS, exhibit reduced virulence factor production in EVPL. We also show that lasR mutants grow as well as or better than a corresponding wild-type strain in EVPL. lasR mutants frequently and repeatedly arise during chronic CF lung infection, but the evolutionary forces governing their appearance and spread are not clear. Our data are not consistent with the hypothesis that lasR mutants act as social “cheats” in the lung; rather, our results support the hypothesis that lasR mutants are more adapted to the lung environment. More generally, this model will facilitate improved studies of microbial disease, especially studies of how cells of the same and different species interact in polymicrobial infections in a spatially structured environment. PMID:24866798

  2. Mutant mice: experimental organisms as materialised models in biomedicine.

    PubMed

    Huber, Lara; Keuck, Lara K

    2013-09-01

    Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease.

  3. Experimental tests of the standard model.

    SciTech Connect

    Nodulman, L.

    1998-11-11

    The title implies an impossibly broad field, as the Standard Model includes the fermion matter states, as well as the forces and fields of SU(3) x SU(2) x U(1). For practical purposes, I will confine myself to electroweak unification, as discussed in the lectures of M. Herrero. Quarks and mixing were discussed in the lectures of R. Aleksan, and leptons and mixing were discussed in the lectures of K. Nakamura. I will essentially assume universality, that is flavor independence, rather than discussing tests of it. I will not pursue tests of QED beyond noting the consistency and precision of measurements of {alpha}{sub EM} in various processes including the Lamb shift, the anomalous magnetic moment (g-2) of the electron, and the quantum Hall effect. The fantastic precision and agreement of these predictions and measurements is something that convinces people that there may be something to this science enterprise. Also impressive is the success of the ''Universal Fermi Interaction'' description of beta decay processes, or in more modern parlance, weak charged current interactions. With one coupling constant G{sub F}, most precisely determined in muon decay, a huge number of nuclear instabilities are described. The slightly slow rate for neutron beta decay was one of the initial pieces of evidence for Cabbibo mixing, now generalized so that all charged current decays of any flavor are covered.

  4. L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of this paper was to investigate the role of porcine basophils in protective immunity. Experimental pigs were infected with 1,000 Ascaris suum eggs daily for 21 days. Control pigs were maintained helminth-free. Circulating porcine basophils were isolated from the anti-coagulated whole blood ...

  5. The Standard Solar Model versus Experimental Observations

    NASA Astrophysics Data System (ADS)

    Manuel, O.

    2000-12-01

    The standard solar model (ssm) assumes the that Sun formed as a homogeneous body, its interior consists mostly of hydrogen, and its radiant energy comes from H-fusion in its core. Two sets of measurements indicate the ssm is wrong: 1. Analyses of material in the planetary system show that - (a) Fe, O, Ni, Si, Mg, S and Ca have high nuclear stability and comprise 98+% of ordinary meteorites that formed at the birth of the solar system; (b) the cores of inner planets formed in a central region consisting mostly of heavy elements like Fe, Ni and S; (c) the outer planets formed mostly from elements like H, He and C; and (d) isotopic heterogeneities accompanied these chemical gradients in debris of the supernova that exploded here 5 billion years ago to produce the solar system (See Origin of the Elements at http://www.umr.edu/õm/). 2. Analyses of material coming from the Sun show that - (a) there are not enough neutrinos for H-fusion to be its main source of energy; (b) light-weight isotopes (mass =L) of He, Ne, Ar, Kr and Xe in the solar wind are enriched relative to heavy isotopes (mass = H) by a factor, f, where log f = 4.56 log [H/L] -- - Eq. (1); (c) solar flares by-pass 3.4 of these 9-stages of diffusion and deplete the light-weight isotopes of He, Ne, Mg and Ar by a factor, f*, where log f* = -1.7 log [H/L] --- Eq. (2); (d) proton-capture on N-14 increased N-15 in the solar wind over geologic time; and (e) solar flares dredge up nitrogen with less N-15 from this H-fusion reaction. Each observation above is unexplained by ssm. After correcting photospheric abundances for diffusion [Observation 2(b)], the most abundant elements in the bulk sun are Fe, Ni, O, Si, S, Mg and Ca, the same elements that comprise ordinary meteorites [Observation 1(a)]. The probability that Eq. (1) would randomly select these elements from the photosphere, i.e., the likelihood for a meaningless agreement between observations 2(b) and 1(a), is < 2.0E(-33). Thus, ssm does not describe the

  6. Material Characterization of In Vivo and In Vitro Porcine Brain using Shear Wave Elasticity

    PubMed Central

    Urbanczyk, Caryn A.; Palmeri, Mark L.; Bass, Cameron R.

    2015-01-01

    Realistic computer simulation of closed head trauma requires accurate mechanical properties of brain tissue, ideally in vivo. A substantive deficiency of most existing experimental brain data is that properties were identified through in vitro mechanical testing. This study develops a novel application of shear wave elasticity imaging (SWEI) to assess porcine brain tissue shear modulus in vivo. SWEI is a quantitative ultrasound technique that has been used here to examine changes in brain tissue shear modulus as a function of several experimental and physiological parameters. Animal studies were performed using two different ultrasound transducers to explore the differences between physical response with closed skull and open skull arrangements. In vivo intracranial pressure (ICP) in four animal subjects was varied over a relevant physiological range (2-40 mmHg), and was correlated with shear wave speed and stiffness estimates in brain tissue. We found that stiffness does not vary with modulation of ICP. Additional in vitro porcine specimens (n=14) were used to investigate variation in brain tissue stiffness with temperature, confinement, spatial location, and transducer orientation. We found a statistically significant decrease in stiffness with increased temperature (23%) and an increase in stiffness with decreasing external confinement (22 - 37%). This study demonstrated the feasibility of using SWEI to characterize porcine brain tissue both in vitro and in vivo. Our results underline the importance of temperature and skull derived boundary conditions on brain stiffness and suggests that physiological ranges of ICP do not significantly affect in situ brain tissue properties. SWEI allowed for brain material properties to be experimentally-characterized in a physiological setting and provides a stronger basis for assessing brain injury in computational models. PMID:25683220

  7. Identification of porcine polycystic kidney disease 1 (PKD1) gene: molecular cloning, expression profile, and implication in disease model.

    PubMed

    He, Jin; Wang, Qingsong; Ye, Jianhua; Hu, Xiaoxiang; Li, Ning

    2011-12-15

    The polycystic kidney disease 1 (PKD1) gene, which accounts for ~85% of human autosomal dominant polycystic kidney disease (ADPKD) cases, has been extensively studied in human and mouse. Much information about the pathogenesis of and treatments for ADPKD has been gained from the use of mouse models. However, because mouse models pose some limitations, further studies in other model systems are needed to investigate the biological basis of ADPKD. The pig is regarded as an important biomedical model. Thus, we isolated a pig PKD1 homolog and characterized its cDNA sequence, genomic structure, expression profile, alternative splicing, methylation status, protein characteristics, and immunohistochemical features in both neonatal and adult pigs. The pig PKD1 cDNA is 14,209bp long and encodes a 4305-residue polypeptide. The genomic sequence of PKD1 is ~50kb with 46 exons. An alternative splice acceptor site was identified in intron 9. PKD1 is expressed in all tissues tested in both neonatal and adult pigs and exhibits a developmentally regulated expression pattern. Western blotting revealed that the molecular mass of polycystin-1 is ~460kDa, but its expression level is relatively low. Immunohistochemical study of the kidneys shows that polycystin-1 is mainly expressed in the tubular epithelia. Bisulfite methylation analysis of CpG islands in the promoter region does not show a direct correlation between methylation status and expression level among different tissues/cells. The cloning and characterization of pig PKD1 indicates that the pig and human genes are highly similar in length of genomic and cDNA sequences, genomic structure and context, expression patterns, conserved transcription factor binding sites, and the molecular mass of the encoded polycystin-1. These data support our current understanding of PKD1, and suggest that the pig is an ideal candidate for development of an ADPKD disease model. PMID:21945688

  8. Current Experimental Basis for Modeling Ice Accretions on Swept Wings

    NASA Technical Reports Server (NTRS)

    Vargas, Mario

    2005-01-01

    This work presents a review of the experimental basis for modeling ice accretions on swept wings. Experimental work related to ice accretion physics on swept wings conducted between 1954 and 2004 is reviewed. Proposed models or explanations of scallop formations are singled out and discussed. Special emphasis is placed on reviewing the work done to determine the basic macroscopic mechanisms of scallop formation. The role of feather growth and its connection to scallop growth is discussed. Conceptual steps in modeling scallop formations are presented. Research elements needed for modeling are discussed.

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

    PubMed

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

    2000-11-01

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

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

    SciTech Connect

    Hadad, Ivan; Johnstone, Brian H.; Brabham, Jeffrey G.; Blanton, Matthew W.; Rogers, Pamela I.; Fellers, Cory; Solomon, James L.; Merfeld-Clauss, Stephanie; DesRosiers, Colleen M.; Dynlacht, Joseph R.; Coleman, John J.; March, Keith L.

    2010-11-01

    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-cm{sup 2} 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.

  11. Stiffness of Carpentry Connections - Numerical Modelling vs. Experimental Test

    NASA Astrophysics Data System (ADS)

    Kekeliak, Miloš; Gocál, Jozef; Vičan, Josef

    2015-12-01

    In this paper, numerical modelling of the traditional carpentry connection with mortise and tenon is presented. Numerical modelling is focused on its stiffness and the results are compared to results of experimental tests carried out by (Feio, 2005) [6]. To consider soft behaviour of wood in carpentry connections, which are related to its surface roughness and geometrical accuracy of the contact surfaces, the characteristics of the normal contact stiffness, determined experimentally, are introduced in the numerical model. Parametric study by means of numerical modelling with regard to the sensitivity of connection stiffness to contact stiffness is presented. Based on the study results, in conclusion there are presented relevant differences between the results of numerical modelling and experimental tests (Feio, 2005) [6].

  12. In vitro culturing of porcine tracheal mucosa as an ideal model for investigating the influence of drugs on human respiratory mucosa

    PubMed Central

    Siefer, Oliver; Zheng, Meihua; Walger, Martin; Mickenhagen, Axel

    2008-01-01

    It has been previously shown that fresh mucosa from different mammals could serve as raw material for in vitro culturing with the differentiation of cilia, which are the most important morphological structures for the function of the mucociliary system. Increasing legal restrictions on the removal of human tissue and changing surgical techniques have led to a lack of fresh human mucosa for culturing. Most of the animals that have been used as donors up to now are genetically not very close to human beings and must all be sacrificed for such studies. We, therefore, established a modified system of culturing mucosa cells from the trachea of pigs, which is available as a regular by-product after slaughtering. With respect to the possibility of developing “beating” cilia, it could be shown that the speed of cell proliferation until adhesion to the coated culture dishes, the formation of conjunctions of cell clusters and the proliferation of cilia were comparable for porcine and human mucosa. Moreover, it could be demonstrated that the porcine cilia beat frequency of 7.57 ± 1.39 Hz was comparable to the human mucosa cells beat frequency of 7.3 ± 1.4 Hz and that this beat frequency was absolutely constant over the investigation time of 360 min. In order to prove whether the reaction to different drugs is comparable between the porcine and human cilia, we initially tested benzalkonium chloride, which is known to be toxic for human cells, followed by naphazoline, which we found in previous studies on human mucosa to be non-toxic. The results clearly showed that the functional and morphological reactions of the porcine ciliated cells to these substances were similar to the reaction we found in the in vitro cultured human mucosa. PMID:18458926

  13. Combustion modeling for experimentation in a space environment

    NASA Technical Reports Server (NTRS)

    Berlad, A. L.

    1974-01-01

    The merits of combustion experimentation in a space environment are assessed, and the impact of such experimentation on current theoretical models is considered. It is noted that combustion theory and experimentation for less than normal gravitational conditions are incomplete, inadequate, or nonexistent. Extensive and systematic experimentation in a space environment is viewed as essential for more adequate and complete theoretical models of such processes as premixed flame propagation and extinction limits, premixed flame propagation in droplet and particle clouds, ignition and autoignition in premixed combustible media, and gas jet combustion of unpremixed reactants. Current theories and models in these areas are described, and some combustion studies that can be undertaken in the Space Shuttle Program are proposed, including crossed molecular beam, turbulence, and upper pressure limit (of gases) studies.

  14. Combined experimental/analytical modeling of shell/payload structures

    SciTech Connect

    Martinez, D.R.; Miller, A.K.; Carne, T.G.

    1985-12-01

    This study evaluates the accuracy of computed modal frequencies obtained from a combined experimental/analytical model of a shell/payload structure. A component mode synthesis technique was used which incorporated free modes and residual effects. The total structure is physically divided into the two subsystems which are connected through stiff joints. The payload was tested to obtain its free-free modes, while a finite element model of the shell was analyzed to obtain its modal description. Both the translational and rotational components of the experimental mode shapes at the payload interface were used in the coupling. Sensitivity studies were also performed to determine the effect of neglecting the residual terms of the payload. Results from a previous study of a combined experimental/analytical model for a beam structure are also given. The beam structure was used to examine the basic procedures and difficulties in experimentally measuring, and analytically accounting for the rotational and residual quantities.

  15. Effect of Negative Pressure Therapy on the Inflammatory Response of the Intestinal Microenvironment in a Porcine Septic Model

    PubMed Central

    Norbury, Kenneth C.; Moyer, Mary Pat

    2015-01-01

    In a swine model of ischemia/reperfusion injury coupled with sepsis, we have previously shown attenuation of secondary organ injury and decreased mortality with negative pressure therapy (NPT). We hypothesized that NPT modulates the intestinal microenvironment by mediating the innate immune system. Sepsis was induced in 12 anesthetized female pigs. Group 1 (n = 6) was decompressed at 12 hrs after injury (T12) and treated with standard of care (SOC), and group 2 (n = 6) with NPT for up to T48. Immunoparalysis was evident as lymphocytopenia at T24 in both groups; however, survival was improved in the NPT group versus SOC (Odds ratio = 4.0). The SOC group showed significant reduction in lymphocyte numbers compared to NPT group by T48 (p < 0.05). The capacity of peritoneal fluid to stimulate a robust reactive oxygen species response in vitro was greater for the NPT group, peaking at T24 for both M1 (p = 0.0197) and M2 macrophages (p = 0.085). Plasma elicited little if any effect which was confirmed by microarray analysis. In this septic swine model NPT appeared to modulate the intestinal microenvironment, facilitating an early robust, yet transient, host defense mediated by M1 and M2 macrophages. NPT may help overcome immunoparalysis that occurs during inflammatory response to septic injury. PMID:26294849

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

    PubMed Central

    Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E.; Audi, Said; Zimmer, Michael; Holly, Thomas A; Lee, Daniel; Zhu, Bao; Zhu, Haibo; Zhao, Ming

    2015-01-01

    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 was 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 3.23 ± 0

  17. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

    PubMed Central

    Bradley, Jessica M.; Islam, Kazi N.; Polhemus, David J.; Donnarumma, Erminia; Brewster, Luke P.; Tao, Ya-Xiong; Goodchild, Traci T.

    2015-01-01

    Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg·kg−1·day−1 bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation. PMID:25957218

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

    PubMed Central

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

    2015-01-01

    Background Endovascular repair of aortic aneurysms has a higher incidence of late complications, and open conversion (OC) associated with high mortality may be required. As alternatives to OCs, we propose minimal invasive laparo-/thoracoscopic approaches, either to control endoleaks after endovascular repair, or to convert non-endovascular treatable cases due to a hostile neck anatomy by inserting a peri-aortic PTFE collar before endovascular repair. Such interventions may reduce complications and the necessity for OCs in the future. Methods In twelve pigs, were 10 had infra-/juxtrarenal AAAs, externally placed collars/aneuwraps around the proximal AAA neck and just below the left subclavian artery and division of the aortic side branches were carried out laparo-and thoracoscopically. Results For the laparoscopic and thoracoscopic procedures respectively, mean operative time was 143 ± 41 min and 86 ± 51 min and a mean of 2.6 and 2.25 aortic side branches were ligated/divided. For both procedures, the last half in the series were carried out significantly faster (p < 0.05) indicating a learning curve. Blood loss was minimal and no procedure related complications were seen. 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. PMID:26793311

  19. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease.

    PubMed

    Bradley, Jessica M; Islam, Kazi N; Polhemus, David J; Donnarumma, Erminia; Brewster, Luke P; Tao, Ya-Xiong; Goodchild, Traci T; Lefer, David J

    2015-07-15

    Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.

  20. Design and Implementation of an Experimental Segway Model

    NASA Astrophysics Data System (ADS)

    Younis, Wael; Abdelati, Mohammed

    2009-03-01

    The segway is the first transportation product to stand, balance, and move in the same way we do. It is a truly 21st-century idea. The aim of this research is to study the theory behind building segway vehicles based on the stabilization of an inverted pendulum. An experimental model has been designed and implemented through this study. The model has been tested for its balance by running a Proportional Derivative (PD) algorithm on a microprocessor chip. The model has been identified in order to serve as an educational experimental platform for segways.

  1. Experimental study and modeling of a novel magnetorheological elastomer isolator

    NASA Astrophysics Data System (ADS)

    Yang, Jian; Du, Haiping; Li, Weihua; Li, Yancheng; Li, Jianchun; Sun, Shuaishuai; Deng, H. X.

    2013-11-01

    This paper reports an experimental setup aiming at evaluating the performance of a newly designed magnetorheological elastomer (MRE) seismic isolator. As a further effort to explore the field-dependent stiffness/damping properties of the MRE isolator, a series of experimental testing were conducted. Based upon the analysis of the experimental responses and the characteristics of the MRE isolator, a new model that is capable of reproducing the unique MRE isolator dynamics behaviors is proposed. The validation results verify the model’s effectiveness to portray the MRE isolator. A study on the field-dependent parameters is then provided to make the model valid with fluctuating magnetic fields. To fully explore the mechanism of the proposed model, an investigation relating the dependence of the proposed model on every parameter is carried out.

  2. Modeling, Robust Control, and Experimental Validation of a Supercavitating Vehicle

    NASA Astrophysics Data System (ADS)

    Escobar Sanabria, David

    This dissertation considers the mathematical modeling, control under uncertainty, and experimental validation of an underwater supercavitating vehicle. By traveling inside a gas cavity, a supercavitating vehicle reduces hydrodynamic drag, increases speed, and minimizes power consumption. The attainable speed and power efficiency make these vehicles attractive for undersea exploration, high-speed transportation, and defense. However, the benefits of traveling inside a cavity come with difficulties in controlling the vehicle dynamics. The main challenge is the nonlinear force that arises when the back-end of the vehicle pierces the cavity. This force, referred to as planing, leads to oscillatory motion and instability. Control technologies that are robust to planing and suited for practical implementation need to be developed. To enable these technologies, a low-order vehicle model that accounts for inaccuracy in the characterization of planing is required. Additionally, an experimental method to evaluate possible pitfalls in the models and controllers is necessary before undersea testing. The major contribution of this dissertation is a unified framework for mathematical modeling, robust control synthesis, and experimental validation of a supercavitating vehicle. First, we introduce affordable experimental methods for mathematical modeling and controller testing under planing and realistic flow conditions. Then, using experimental observations and physical principles, we create a low-order nonlinear model of the longitudinal vehicle motion. This model quantifies the planing uncertainty and is suitable for robust controller synthesis. Next, based on the vehicle model, we develop automated tools for synthesizing controllers that deliver a certificate of performance in the face of nonlinear and uncertain planing forces. We demonstrate theoretically and experimentally that the proposed controllers ensure higher performance when the uncertain planing dynamics are

  3. Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure.

    PubMed

    Defterevos, Georgios; Nastos, Constantinos; Papalois, Apostolos; Kalimeris, Konstantinos; Margelos, Vassileios; Fragulidis, George; Pafiti, Agathi; Mikrovas, Aggeliki; Nomikos, Tzortzis; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2016-08-01

    Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study. PMID:27094211

  4. Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

    PubMed Central

    Schlimp, Christoph J.; Solomon, Cristina; Keibl, Claudia; Zipperle, Johannes; Nürnberger, Sylvia; Öhlinger, Wolfgang; Redl, Heinz; Schöchl, Herbert

    2014-01-01

    be time consuming. LEVEL OF EVIDENCE Prospective, randomized, therapeutic feasibility study in an animal model, level V. PMID:24747454

  5. Computational modeling of epilepsy for an experimental neurologist

    PubMed Central

    Holt, Abbey B.; Netoff, Theoden I.

    2013-01-01

    Computational modeling can be a powerful tool for an experimentalist, providing a rigorous mathematical model of the system you are studying. This can be valuable in testing your hypotheses and developing experimental protocols prior to experimenting. This paper reviews models of seizures and epilepsy at different scales, including cellular, network, cortical region, and brain scales by looking at how they have been used in conjunction with experimental data. At each scale, models with different levels of abstraction, the extraction of physiological detail, are presented. Varying levels of detail are necessary in different situations. Physiologically realistic models are valuable surrogates for experimental systems because, unlike in an experiment, every parameter can be changed and every variable can be observed. Abstract models are useful in determining essential parameters of a system, allowing the experimentalist to extract principles that explain the relationship between mechanisms and the behavior of the system. Modeling is becoming easier with the emergence of platforms dedicated to neuronal modeling and databases of models that can be downloaded. Modeling will never be a replacement for animal and clinical experiments, but it should be a starting point in designing experiments and understanding their results. PMID:22617489

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

    PubMed Central

    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 PMWS, subclinical disease (reduce growth without evident clinical signs) or remain healthy (normal growth and no clinical signs), depending on the farm level PMWS severity. This PMWS severity measure accounted for the level of post-weaning mortality, PMWS morbidity and proportion of PCV2 infected pigs observed on farms. The model generated six outcomes: infected pigs with PMWS that die (PMWS-D); infected pigs with PMWS that recover (PMWS-R); subclinical pigs that die (Sub-D); subclinical pigs that reach slaughter age (Sub-S); healthy pigs sold (H-S); and pigs, infected or non-infected by PCV2, that die due to non-PCV2 related causes (nonPCV2-D). Enterprise and partial budget analyses were used to assess the deficit/profits and the extra costs/extra benefits of a change in disease status, respectively. Results from the economic analysis at pig level were combined with the disease model's estimates of the proportion of different pigs produced at different severity scores to assess the cost of PMWS and subclinical disease at farm level, and these were then extrapolated to estimate costs at national level. The net profit for a H-S pig was £19.2. The mean loss for a PMWS-D pig was £84.1 (90% CI: 79.6–89.1), £24.5 (90% CI: 15.1–35.4) for a PMWS-R pig, £82.3 (90% CI: 78.1–87.5) for a Sub-D pig, and £8.1 (90% CI: 2.18–15.1) for a Sub-S pig. At farm level, the greatest proportion of negative economic impact was attributed to PCV2 subclinical pigs. The economic impact for the

  7. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 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...

  8. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 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...

  9. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 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...

  10. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 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...

  11. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2010 CFR

    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...

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Finite element modeling for validation of structural damage identification experimentation.

    SciTech Connect

    Stinemates, D. W.; Bennett, J. G.

    2001-01-01

    The project described in this report was performed to couple experimental and analytical techniques in the field of structural health monitoring and darnage identification. To do this, a finite dement model was Constructed of a simulated three-story building used for damage identification experiments. The model was used in conjunction with data from thie physical structure to research damage identification algorithms. Of particular interest was modeling slip in joints as a function of bolt torque and predicting the smallest change of torque that could be detected experimentally. After being validated with results from the physical structure, the model was used to produce data to test the capabilities of damage identification algorithms. This report describes the finite element model constructed, the results obtained, and proposed future use of the model.

  14. An Experimentally Determined Evolutionary Model Dramatically Improves Phylogenetic Fit

    PubMed Central

    Bloom, Jesse D.

    2014-01-01

    All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses. PMID:24859245

  15. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass†

    PubMed Central

    Aass, Terje; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Dahle, Geir Olav; Chambers, David J.; Markou, Thomais; Eliassen, Finn; Urban, Malte; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-01-01

    OBJECTIVES Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure–conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0

  16. An Experimental Study and Constitutive Modeling of Saturated Porous Rocks

    NASA Astrophysics Data System (ADS)

    Xie, S. Y.; Shao, J. F.

    2015-01-01

    This paper is devoted to the experimental characterization and constitutive modeling of saturated porous rocks. A typical porous chalk is investigated. Drained hydrostatic and triaxial compression tests are first performed to characterize the basic mechanical behavior of chalk. Drained triaxial tests with constant interstitial pressure are then carried out to study the effects of interstitial pressure on the plastic deformation and failure criterion. Finally, undrained triaxial compression tests are performed to investigate poromechanical coupling in saturated conditions. Based on the experimental data and some relevant micromechanical considerations, a micromechanics-based plastic model is proposed and extended to poroplastic coupling using the effective stress concept. The proposed model is verified through comparisons between the numerical results and experimental data for both drained and undrained tests.

  17. Experimental Verification of Structural-Acoustic Modelling and Design Optimization

    NASA Astrophysics Data System (ADS)

    MARBURG, S.; BEER, H.-J.; GIER, J.; HARDTKE, H.-J.; RENNERT, R.; PERRET, F.

    2002-05-01

    A number of papers have been published on the simulation of structural-acoustic design optimization. However, extensive work is required to verify these results in practical applications. Herein, a steel box of 1·0×1·1×1·5 m with an external beam structure welded on three surface plates was investigated. This investigation included experimental modal analysis and experimental measurements of certain noise transfer functions (sound pressure at points inside the box due to force excitation at beam structure). Using these experimental data, the finite element model of the structure was tuned to provide similar results. With a first structural mode at less than 20 Hz, the reliable frequency range was identified up to about 60 Hz. Obviously, the finite element model could not be further improved only by mesh refinement. The tuning process will be explained in detail since there was a number of changes that helped to improve the structure. Other changes did not improve the structure. Although this model of the box could be expected as a rather simple structure, it can be considered to be a complex structure for simulation purposes. A defined modification of the physical model verified the simulation model. In a final step, the optimal location of stiffening beam structures was predicted by simulation. Their effect on the noise transfer function was experimentally verified. This paper critically discusses modelling techniques that are applied for structural-acoustic simulation of sedan bodies.

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

    PubMed

    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

  19. Experimental models of hepatotoxicity related to acute liver failure.

    PubMed

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  20. Experimental models of hepatotoxicity related to acute liver failure

    PubMed Central

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  1. Experimental models of hepatotoxicity related to acute liver failure.

    PubMed

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure.

  2. Experimental validation of flexible robot arm modeling and control

    NASA Technical Reports Server (NTRS)

    Ulsoy, A. Galip

    1989-01-01

    Flexibility is important for high speed, high precision operation of lightweight manipulators. Accurate dynamic modeling of flexible robot arms is needed. Previous work has mostly been based on linear elasticity with prescribed rigid body motions (i.e., no effect of flexible motion on rigid body motion). Little or no experimental validation of dynamic models for flexible arms is available. Experimental results are also limited for flexible arm control. Researchers include the effects of prismatic as well as revolute joints. They investigate the effect of full coupling between the rigid and flexible motions, and of axial shortening, and consider the control of flexible arms using only additional sensors.

  3. Modeling and managing experimental data using FuGE.

    PubMed

    Jones, Andrew R; Lister, Allyson L; Hermida, Leandro; Wilkinson, Peter; Eisenacher, Martin; Belhajjame, Khalid; Gibson, Frank; Lord, Phil; Pocock, Matthew; Rosenfelder, Heiko; Santoyo-Lopez, Javier; Wipat, Anil; Paton, Norman W

    2009-06-01

    The Functional Genomics Experiment data model (FuGE) has been developed to increase the consistency and efficiency of experimental data modeling in the life sciences, and it has been adopted by a number of high-profile standardization organizations. FuGE can be used: (1) directly, whereby generic modeling constructs are used to represent concepts from specific experimental activities; or (2) as a framework within which method-specific models can be developed. FuGE is both rich and flexible, providing a considerable number of modeling constructs, which can be used in a range of different ways. However, such richness and flexibility also mean that modelers and application developers have choices to make when applying FuGE in a given context. This paper captures emerging best practice in the use of FuGE in the light of the experience of several groups by: (1) proposing guidelines for the use and extension of the FuGE data model; (2) presenting design patterns that reflect recurring requirements in experimental data modeling; and (3) describing a community software tool kit (STK) that supports application development using FuGE. We anticipate that these guidelines will encourage consistent usage of FuGE, and as such, will contribute to the development of convergent data standards in omics research.

  4. Sound transmission in porcine thorax through airway insonification.

    PubMed

    Peng, Ying; Dai, Zoujun; Mansy, Hansen A; Henry, Brian M; Sandler, Richard H; Balk, Robert A; Royston, Thomas J

    2016-04-01

    Many pulmonary injuries and pathologies may lead to structural and functional changes in the lungs resulting in measurable sound transmission changes on the chest surface. Additionally, noninvasive imaging of externally driven mechanical wave motion in the chest (e.g., using magnetic resonance elastography) can provide information about lung structural property changes and, hence, may be of diagnostic value. In the present study, a comprehensive computational simulation (in silico) model was developed to simulate sound wave propagation in the airways, lung, and chest wall under normal and pneumothorax conditions. Experiments were carried out to validate the model. Here, sound waves with frequency content from 50 to 700 Hz were introduced into airways of five porcine subjects via an endotracheal tube, and transmitted waves were measured by scanning laser Doppler vibrometry at the chest wall surface. The computational model predictions of decreased sound transmission with pneumothorax were consistent with experimental measurements. The in silico model can also be used to visualize wave propagation inside and on the chest wall surface for other pulmonary pathologies, which may help in developing and interpreting diagnostic procedures that utilize sound and vibration.

  5. Comparison of hybrid Hall thruster model to experimental measurements

    NASA Astrophysics Data System (ADS)

    Scharfe, Michelle K.; Gascon, Nicolas; Cappelli, Mark A.; Fernandez, Eduardo

    2006-08-01

    A two-dimensional hybrid particle-in-cell numerical model has been constructed in the radial-axial plane with the intent of examining the physics governing Hall thruster operation. The electrons are treated as a magnetized quasi-one-dimensional fluid and the ions are treated as collisionless, unmagnetized discrete particles. The anomalously high electron conductivity experimentally observed in Hall thrusters is accounted for using experimental measurements of electron mobility in the Stanford Hall Thruster. While an experimental mobility results in improved simulation of electron temperature and electric potential relative to a Bohm-type model, results suggest that energy losses due to electron wall interactions may also be an important factor in accurately simulating plasma properties. Using a simplified electron wall damping model modified to produce general agreement with experimental measurements, an evaluation is made of differing treatments of electron mobility, background gas, neutral wall interactions, and charge exchange collisions. Although background gas results in two populations of neutrals, the increased neutral density has little effect on other plasma properties. Diffuse neutral wall interactions are in better agreement with experimental measurements than specular scattering. Also, charge exchange collisions result in an increase in average neutral velocity of 11% and a decrease in average ion velocity of 4% near the exit plane. The momentum exchange that occurs during charge exchange collisions is found to be negligible.

  6. Experimental, numerical and analytical models of mantle starting plumes

    NASA Astrophysics Data System (ADS)

    Coulliette, D. L.; Loper, D. E.

    1995-12-01

    The results of a combined experimental, numerical and analytical investigation of starting thermal plumes are described, to obtain a better perspective on plumes within the Earth's mantle. Thermal plumes were generated experimentally in a tank of corn syrup by means of an electrical heater. Viscosity ratios of 400, 30 000, and 10 8 were generated by varying the temperature of the tank. Plumes for the smaller ratios had the traditional 'balloon-on-astring' shape, but that at the highest ratio had a novel morphology. The plume heads in the first two cases were observed to rise at roughly a constant speed, in contrast to most previous studies which found the plume heads to accelerate. Loss of buoyancy from the plume head owing to heat loss is believed to be responsible for this difference. Starting plumes were simulated numerically using an axisymmetric, finite-element code to solve the Boussinesq equations at finite Prandtl numbers. The constant rise speed observed experimentally was confirmed by the numerical simulation for the viscosity ratios of 400 and 30 000, but numerical instability prevented simulation of the case with a viscosity ratio of 10 8. There was very good agreement between the experimental and numerical rise speeds. An analytical model was developed which reduces to previous models in limiting cases. This parameterization gives better agreement with the experimental and numerical results than does any previous model.

  7. A numerical cloud model for the support of laboratory experimentation

    NASA Technical Reports Server (NTRS)

    Hagen, D. E.

    1979-01-01

    A numerical cloud model is presented which can describe the evolution of a cloud starting from moist aerosol-laden air through the diffusional growth regime. The model is designed for the direct support of cloud chamber laboratory experimentation, i.e., experiment preparation, real-time control and data analysis. In the model the thermodynamics is uncoupled from the droplet growth processes. Analytic solutions for the cloud droplet growth equations are developed which can be applied in most laboratory situations. The model is applied to a variety of representative experiments.

  8. Experimental Models of Microvascular Immunopathology: The Example of Cerebral Malaria

    PubMed Central

    El-Assaad, Fatima; Combes, Valery; Grau, Georges ER

    2015-01-01

    Human cerebral malaria is a severe and often lethal complication of Plasmodium falciparum infection. Complex host and parasite interactions should the precise mechanisms involved in the onset of this neuropathology. Adhesion of parasitised red blood cells and host cells to endothelial cells lead to profound endothelial alterations that trigger immunopathological changes, varying degrees of brain oedema and can compromise cerebral blood flow, cause cranial nerve dysfunction and hypoxia. Study of the cerebral pathology in human patients is limited to clinical and genetic field studies in endemic areas, thus cerebral malaria (CM) research relies heavily on experimental models. The availability of malaria models allows study from the inoculation of Plasmodium to the onset of disease and permit invasive experiments. Here, we discuss some aspects of our current understanding of CM, the experimental models available and some important recent findings extrapolated from these models. PMID:26430675

  9. Microbiome and Asthma: What Have Experimental Models Already Taught Us?

    PubMed Central

    Bonamichi-Santos, R.; Aun, M. V.; Agondi, R. C.; Kalil, J.; Giavina-Bianchi, P.

    2015-01-01

    Asthma is a chronic inflammatory disease that imposes a substantial burden on patients, their families, and the community. Although many aspects of the pathogenesis of classical allergic asthma are well known by the scientific community, other points are not yet understood. Experimental asthma models, particularly murine models, have been used for over 100 years in order to better understand the immunopathology of asthma. It has been shown that human microbiome is an important component in the development of the immune system. Furthermore, the occurrence of many inflammatory diseases is influenced by the presence of microbes. Again, experimental models of asthma have helped researchers to understand the relationship between the microbiome and respiratory inflammation. In this review, we discuss the evolution of murine models of asthma and approach the major studies involving the microbiome and asthma. PMID:26266269

  10. The immediate effect of repeated loading on the compressive strength of young porcine lumbar spine.

    PubMed

    Thoreson, Olof; Baranto, Adad; Ekström, Lars; Holm, Sten; Hellström, Mikael; Swärd, Leif

    2010-05-01

    The human spine is exposed to repeated loading during daily activities and more extremely during sports. Despite this, there remains a lack of knowledge regarding the immediate effects on the spine due to this mode of loading. Age-specific spinal injury patterns has been demonstrated and this implies differences in reaction to load mode and load history The purpose of the present study was to investigate the impact of cyclic pre-loading on the biomechanical properties and fracture patterns of the adolescent spine in an experimental model. Eight functional spinal units from four young porcine spines were harvested. The functional spinal units were cyclic loaded with 20,000 cycles and then axially compressed to failure. The compression load at failure, ultimate stress and viscoelastic parameters were calculated. The functional spinal units were examined with plain radiography, computer tomography and MRI before and after the loading, and finally macroscopically and histologically. The median compression load at failure in this study was 8.3 kN (range 5.6-8.7 kN). The median deformation for all cases was 2.24 mm (range 2.30-2.7 mm) and stiffness was 3.45 N/mm (range 3.5-4.5 N/mm). A fracture was seen on radiograph in one case, on CT and macroscopically in seven, and on MRI and histologically in all eight cases. The cyclic loaded functional spinal units in the present study were not more sensitive to axial compression than non-cyclic loaded functional spinal units from young porcine. The endplate and the growth zone were the weakest part in the cyclic loaded functional spinal units. Disc signal reduction and disc height reduction was found on MRI. The E-modulus value found in this study was of the same order of magnitude as found by others using a porcine animal model.

  11. Developing an Experimental Model of Vascular Toxicity in Embryonic Zebrafish

    EPA Science Inventory