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Pig Model (pig + model)
Kinds of Pig Model Selected AbstractsCryolipolysis for Noninvasive Fat Cell Destruction: Initial Results from a Pig ModelDERMATOLOGIC SURGERY, Issue 10 2009BRIAN ZELICKSON MD BACKGROUND Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (,43.8 mW/cm2), one at CIF 24.9 (,44.7 mW/cm2), and one at CIF 25.4 (,45.6 mW/cm2). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold-induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3-month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids. [source] The Effect of Betamethasone Treatment on Neuroactive Steroid Synthesis in a Foetal Guinea Pig Model of Growth RestrictionJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2010A. A. McKendry There are ongoing concerns that antenatal corticosteroids, which are administered to women at high risk of delivering preterm to reduce the incidence of respiratory distress syndrome, have adverse effects on foetal brain development and subsequent effects on behaviour and learning, when administered as repeated courses. The present study aimed to examine whether repeated betamethasone treatment alters the expression of the key-rate limiting enzyme, 5,-reductase, in the synthetic pathway of the potent neuroactive steroid allopregnanolone in the brain and placenta and whether this effect is potentiated in growth restricted foetuses. To investigate this, pregnant guinea pigs carrying either control (sham surgery) or growth-restricted foetuses were treated with vehicle or betamethasone (1 mg/kg/day) for 4 days prior to sacrifice (65d). Placental insufficiency was induced by the ablation of uterine artery branches supplying each placenta at mid gestation, resulting in foetal growth restriction characterised by ,brain sparing'. Real-time reverse transcriptase polymerase chain reaction was used to determine relative 5,-reductase type 1 and 2 mRNA expression in the placenta and brain. Immunohistochemistry was used to examine the glial fibrillary acidic protein (GFAP) expression in the subcortical white matter, CA1 and dentate regions of the hippocampus. 5,-reductase type 2 mRNA expression in the brain was markedly reduced by betamethasone treatment in male foetuses compared to vehicle-treated controls but not in female foetuses. In addition, 5,-reductase type 1 expression in the brain was increased by growth restriction and/or betamethasone treatment in female foetuses but expression in males foetuses did not increase. 5,-reductase type 2 expression in the placenta was markedly reduced by betamethasone treatment compared to vehicle-treated control. Intrauterine growth restriction and betamethasone treatment reduced GFAP expression in the CA1 region of the hippocampus in the brains of male but not female foetuses. These data indicate that betamethasone treatment suppresses placental expression and has sexually dimorphic effects on expression of neuroactive steroid synthetic enzymes in the brain. These actions may lead to adverse effects on the developing brain, particularly in male foetuses, such as the observed effects on GFAP expression. [source] Impaired Terminal Differentiation of Pulmonary Macrophages in a Guinea Pig Model of Chronic Ethanol IngestionALCOHOLISM, Issue 10 2009Sheena D. Brown Background:, Alcoholic patients have an increased risk of respiratory infections, which is partially due to an impaired immune response of alveolar macrophages. The mechanisms by which alcohol impairs alveolar macrophage function are poorly understood. In this study, we demonstrated in a guinea pig model that chronic ethanol ingestion significantly impaired alveolar macrophage differentiation and function. Methods:, Isolated alveolar macrophages were separated into 4 different subpopulations with varying densities and levels of maturation. Results: Compared to control values, chronic ethanol ingestion decreased the percentage of alveolar macrophages in the mature fractions by ,60%. Alveolar macrophage function in each subpopulation was determined by measuring phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus aureus. Alveolar macrophages from ethanol-fed animals had ,80% decrease in the phagocytic index. Western blot and immunohistochemical analysis of the differential markers granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor , (GM-CSFR-,), PU.1, CD11c, and CD11b verified that alcoholic macrophages displayed impaired terminal differentiation. While oral supplementation with the glutathione precursor S -adenosyl-methionine (SAM) did not alter the maturational status of control animals, SAM supplementation shifted the distribution of macrophages to more mature fractions, normalized the phagocytic index; as well as normalized expression of CD11c, CD11b, PU.1, and GM-CSFR-,. Chronic ethanol ingestion also impaired the differentiation status of interstitial macrophages which was normalized by SAM supplementation. Conclusion:, This improvement in the maturational status suggested that ethanol-induced oxidant stress is a central feature in impaired terminal differentiation of macrophages in the interstitial and alveolar space. Therefore, strategies targeting pulmonary oxidant stress may restore macrophage differentiation and function even after chronic ethanol ingestion. [source] Measurement of Lens Protein Aggregation in Vivo Using Dynamic Light Scattering in a Guinea Pig/UVA Model for Nuclear CataractPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2008M. Francis Simpanya The role of UVA radiation in the formation of human nuclear cataract is not well understood. We have previously shown that exposing guinea pigs for 5 months to a chronic low level of UVA light produces increased lens nuclear light scattering and elevated levels of protein disulfide. Here we have used the technique of dynamic light scattering (DLS) to investigate lens protein aggregation in vivo in the guinea pig/UVA model. DLS size distribution analysis conducted at the same location in the lens nucleus of control and UVA-irradiated animals showed a 28% reduction in intensity of small diameter proteins in experimental lenses compared with controls (P < 0.05). In addition, large diameter proteins in UVA-exposed lens nuclei increased five-fold in intensity compared to controls (P < 0.05). The UVA-induced increase in apparent size of lens nuclear small diameter proteins was three-fold (P < 0.01), and the size of large diameter aggregates was more than four-fold in experimental lenses compared with controls. The diameter of crystallin aggregates in the UVA-irradiated lens nucleus was estimated to be 350 nm, a size able to scatter light. No significant changes in protein size were detected in the anterior cortex of UVA-irradiated lenses. It is presumed that the presence of a UVA chromophore in the guinea pig lens (NADPH bound to zeta crystallin), as well as traces of oxygen, contributed to UVA-induced crystallin aggregation. The results indicate a potentially harmful role for UVA light in the lens nucleus. A similar process of UVA-irradiated protein aggregation may take place in the older human lens nucleus, accelerating the formation of human nuclear cataract. [source] N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen speciesEXPERIMENTAL DERMATOLOGY, Issue 8 2010Bour-Jr Wang Please cite this paper as: N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species. Experimental Dermatology 2010; 19: e191,e200. Abstract Background:, Chromium hypersensitivity is an important issue in occupational skin disease. When hexavalent chromium enters the cell, it can be reduced to trivalent chromium, resulting in the formation of reactive oxygen species (ROS). ROS are considered to play an important role in the progression of allergic contact dermatitis. N -acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. Aims:, We attempted to demonstrate that NAC could inhibit chromium hypersensitivity in a coadjuvant chromium-sensitized albino guinea pig model by counteracting the formation of ROS. Methods:, We utilized a coadjuvant chromium-sensitized albino guinea pig model to evaluate both the severity of the skin reaction by intradermal and epicutaneous elicitation tests and the sensitization rate of chromium hypersensitivity in NAC-treated and NAC-untreated albino guinea pigs (GP). Furthermore, three ROS parameters, including H2O2, malondialdehyde (MDA) levels in the skin and the oxygen radical absorbance capacity (ORAC) in plasma, were analyzed in NAC-treated and NAC-untreated coadjuvant chromium-sensitized albino GP. Results:, The severity of the skin reaction in the intradermal and epicutaneous elicitation test significantly diminished when the albino GP were treated with a dose of 1200 mg/kg/day of NAC. This dose also significantly decreased the sensitization rate of chromium hypersensitivity. In addition, treatment with 1200 mg/kg/day of NAC significantly reduced the H2O2 and MDA levels in the skin and significantly increased the ORAC in the plasma of albino GP. Therefore, NAC could be a potential chemopreventative agent to prevent the progression of chromium hypersensitivity. [source] Iron chelation prevents lung injury after major hepatectomyHEPATOLOGY RESEARCH, Issue 8 2010Konstantinos Kalimeris Aim:, Oxidative stress has been implicated in lung injury following ischemia/reperfusion and resection of the liver. We tested whether alleviating oxidative stress with iron chelation could improve lung injury after extended hepatectomy. Methods:, Twelve adult female pigs subjected to liver ischemia for 150 min, 65,70% hepatectomy and reperfusion of the remnant liver for 24 h were randomized to a desferrioxamine (DF) group (n = 6) which received i.v. desferrioxamine to a total dose of 100 mg/kg during both ischemia and reperfusion, and a control (C) group (n = 6). We recorded hemodynamic and respiratory parameters, plasma interleukin-6 and malondialdehyde levels, as well as liver malondialdehyde and protein carbonyls content. Total non-heme iron was measured in lung and liver. Pulmonary tissue was evaluated histologically for its nitrotyrosine and protein carbonyls content and for superoxide dismutase (SOD) and platelet-activating factor acetylhydrolase (PAF-AcH) activities. Results:, Reperfusion of the remnant liver resulted in gradual deterioration of gas-exchange and pulmonary vascular abnormalities. Iron chelation significantly decreased the oxidative markers in plasma, liver and the lung and lowered activities of pulmonary SOD and PAF-AcH. The improved liver function was followed by improved arterial oxygenation and pulmonary vascular resistance. DF also improved alveolar collapse and inflammatory cell infiltration, while serum interleukin-6 increased. Conclusion:, In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation. [source] A minipig model of high-fat/high-sucrose diet-induced diabetes and atherosclerosisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004Shoumin Xi Summary Type 2 diabetes is a major risk factor of the development of atherosclerosis in humans. However, studies examining mechanisms underlying diabetes-accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models. Pigs have a cardiovascular system that is very similar to that of humans and is useful as a model for human physiology and pathophysiology. In this study, we established a new miniature pig model for studying dyslipidaemia and atherosclerosis in diabetes. Chinese Guizhou minipigs were fed a normal control diet or a high-fat/high-sucrose diet (HFSD) for 6 months. Plasma total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), insulin and glucose were quantified at monthly intervals. The induction of insulin resistance and dysfunction of the pancreatic ,-cell were assessed by oral glucose tolerance test and insulin sensitivity test. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. During the feeding period, mild high plasma TC and TG were induced. At the end of 6 months, in HFSD-fed animals, the adipocytes were hypertrophic, fat deposit in the liver was observed, loss of pancreatic ,-cells was observed, and the aortic fatty streak lesions were clearly present in the animals' aortas. Our study established that miniature pigs that were fed a HFSD without adding dietary cholesterol developed insulin resistance, mild diabetes and atherosclerotic lesions. HFSD-fed miniature pigs may be good animal models for research on the treatment of diabetic dyslipidaemia complicated with atherosclerosis. [source] Systematic evaluation of the highest current threshold for regional anaesthesia in a porcine modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010T. STEINFELDT Background: The purpose of this study was to determine systematically the highest minimal stimulation current threshold for regional anaesthesia in pigs. Methods: In an established pig model for regional anaesthesia, needle placements applying electric nerve stimulation were performed. The primary outcome was the frequency of close needle to nerve placements as assessed by resin injectates and subsequent anatomical evaluation. Following a statistical model (continual reassessment method), the applied output currents were selected to limit the necessary number of punctures, while providing guidance towards the highest output current range. Results: Altogether 186 punctures were performed in 11 pigs. Within the range of 0.3,1.4 mA, no distant needle to nerve placement was found. In the range of 1.5,4.1 mA, 43 distant needle to nerve placements occurred. The range of 1.2,1.4 mA was the highest interval that resulted in a close needle to nerve placement rate of ,95%. Conclusions: In the range of 0.3,1.4 mA, all resin deposition was found to be adjacent to nerve epineurium. The application of minimal current intensities up to 1.4 mA does not obviously lead to a reduction of epineural injectate contacts in pigs. These findings suggest that stimulation current thresholds up to 1.4 mA result in equivalent needle tip localisation in pigs. [source] Twenty-Four Hours Postoperative Results After Orthotopic Cardiac Transplantation in SwineJOURNAL OF CARDIAC SURGERY, Issue 4 2007Matthias Siepe M.D. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation.Materials and Methods: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. Results: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. Conclusions: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated. [source] Role of Wavelength Adaptation in the Initiation, Maintenance, and Pharmacologic Suppression of ReentryJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2001STEVEN D. GIROUARD Ph.D. Wavelength Adaptation and Reentry.Introduction: The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength ,) and the reentrant path length. Because considerable evidence suggests that , changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat-by-beat adaptation of , to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry. Methods and Results: To investigate the dynamic relationship between , and path length during initiation of reentry, optical mapping with voltage-sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer-guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 , M d-sotalol, , was monitored during steady-state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d-sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of , to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the , of the orthodromic impulse adapted to the reentrant path (, < path length). d-Sotalol prevented initiation of VT by altering , adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use-dependence developed after several beats of tachycardia. Conclusion: In an experimental model where ,, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat-to-beat adaptation of , to the dimensions of the reentrant path. [source] Oxidative damage is a potential cause of cone cell death in retinitis pigmentosaJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005JiKui Shen Retinitis pigmentosa (RP) is a prevalent cause of blindness caused by a large number of different mutations in many different genes. The mutations result in rod photoreceptor cell death, but it is unknown why cones die. In this study, we tested the hypothesis that cones die from oxidative damage by performing immunohistochemical staining for biomarkers of oxidative damage in a transgenic pig model of RP. The presence of acrolein- and 4-hydroxynonenal-adducts on proteins is a specific indicator that lipid peroxidation has occurred, and there was strong immunofluorescent staining for both in cone inner segments (IS) of two 10-month-old transgenic pigs in which almost all rods had died, compared to faint staining in two 10-month-old control pig retinas. In 22- and 24-month-old transgenic pigs in which all rods and many cones had died, staining was strong in cone axons and some cell bodies as well as IS indicating progression in oxidative damage between 10 and 22 months. Biomarkers for oxidative damage to proteins and DNA also showed progressive oxidative damage to those macromolecules in cones during the course of RP. These data support the hypothesis that the death of rods results in decreased oxygen consumption and hyperoxia in the outer retina resulting in gradual cone cell death from oxidative damage. This hypothesis has important therapeutic implications and deserves rapid evaluation. © 2005 Wiley-Liss, Inc. [source] The Short-Term Effect on Restenosis and Thrombosis of a Cobalt-Chromium Stent Eluting Two Drugs in a Porcine Coronary Artery ModelJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2009YINGYING HUANG Ph.D. The aim of this article was to study the effect of dual drug-eluting stent (DES) on both restenosis and thrombosis in a porcine coronary artery model. This study reports on the use of two drugs coated on the stent to simultaneously minimize both restenosis and thrombosis. The DES was prepared by spray coating a bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The two-layered dual drug-coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. In vivo animal studies (in a pig model) were then performed for acute thrombosis, inflammation, and restenosis. The results show a significant reduction in restenosis with a stent coated with both drugs compared with the controls (a bare metal stent, a sirolimus-coated, and a pure polymer-coated stent). The reduction in restenosis with a sirolimus/triflusal-eluting stent is associated with an inhibition of inflammation and thrombus formation, suggesting that such dual DES have a role to play for the treatment of coronary artery diseases. [source] Dynamic observation of pulmonary perfusion using continuous arterial spin-labeling in a pig modelJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2001David A. Roberts MD Abstract The continuous arterial spin-labeling (CASL) method of perfusion MRI is used to observe pulmonary perfusion dynamically in an animal model. Specifically, a respiratory-triggered implementation of the CASL method is used with approximate spatial resolution of 0.9 × 1.8 × 5.0 mm (0.008 cc) and 2-minute temporal resolution. Perfusion MRI is performed dynamically during repeated balloon occlusion of a segmental pulmonary artery, as well as during pharmacological stimulation. A total of three Yorkshire pigs were studied. The results demonstrate the ability of the endogenous spin-labeling method to characterize the dynamic changes in pulmonary perfusion that occur during important physiological alterations. J. Magn. Reson. Imaging 2001;14:175,180. © 2001 Wiley-Liss, Inc. [source] Monitoring pulmonary perfusion by electrical impedance tomography: an evaluation in a pig modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009A. FAGERBERG Background: Electrical impedance tomography (EIT) is a non-invasive technique that generates images of impedance distribution. Changes in the pulmonary content of air and blood are major determinants of thoracic impedance. This study was designed to evaluate EIT in monitoring pulmonary perfusion in a wide range of cardiac output. Methods: Eight anaesthetised, mechanically ventilated pigs were fitted with a 16-electrode belt at the mid-thoracic level to generate EIT images that were analysed to determine pulse-synchronous systolic changes in impedance (,Zsys). Stroke volume (SV) was derived using a pulmonary artery catheter. Reductions in cardiac pre-load, and thus pulmonary perfusion, were induced either by inflating the balloon of a Fogarty catheter positioned in the inferior caval vein or by increasing the positive end-expiratory pressure (PEEP). All measurements were performed in a steady state during a short apnoea. Results: Pulse-synchronous changes in ,Zsys were easily discernable during apnoea. Balloon inflation reduced SV to 36% of the baseline, with a corresponding decrease in ,Zsys to 45% of baseline. PEEP reduced SV and ,Zsys to 52% and 44% of the baseline, respectively. Significant correlations between SV and ,Zsys were demonstrated during all measurements (,=0.62) as well as during balloon inflation (,=0.73) and increased PEEP (,=0.40). A Bland,Altman comparison of relative changes in SV and ,Zsys demonstrated a bias of ,7%, with 95% limits of agreement at ,51% and 36%. Conclusions: EIT provided beat-to-beat approximations of pulmonary perfusion that significantly correlated to a wide range of SV values achieved during both extra and intrapulmonary interventions to change cardiac output. [source] Connexin 43 gap junction proteins are up-regulated in remyelinating spinal cordJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2007W.A. Roscoe Abstract Alterations in the expression of gap junction proteins have previously been observed in several diseases affecting the central nervous system; however, the status of connexin 43 (Cx43) has not yet been reported in spinal cord remyelination. We studied Cx43 expression in demyelination and remyelination by using a chronic guinea pig model of experimental allergic encephalomyelitis (EAE). Hartley guinea pigs were immunized with homogenized whole CNS and complete Freund's adjuvant. Animals became chronically ill by day 40 postimmunization, and animals with paralysis were entered into the study. Animals were treated on days 40,60 postimmunization with either saline or drugs that promote remyelination: an adenosine amine congener (100 ,g/kg), an anti-,4-integrin blocker (CT301; ELN 69299; 30 mg/kg), or a combination of both drugs. Remyelination was induced in all drug-treated groups. Cx43 expression was virtually absent in demyelinated lesions of saline-treated controls compared with healthy tissue and normal appearing white matter (P < 0.001), whereas Cx43 was considerably increased (300,500%) in remyelinating lesions of all treatment groups (P < 0.001), most notably in CT301-treated animals. These changes in Cx43 expression indicate that Cx43 may beimportant for recovery from neuroinflammation. © 2007 Wiley-Liss, Inc. [source] Autologous nucleus pulposus primes T cells to develop into interleukin-4-producing effector cells: An experimental study on the autoimmune properties of nucleus pulposusJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009Andrea Geiss Abstract An autoimmune response to herniated nucleus pulposus has been proposed to constitute a pathophysiologic mechanism for inducing sciatica based on the fact that nucleus pulposus under normal conditions is excluded from the development of immunological tolerance. The manifestation of an autoimmune response comprises different steps starting with antigen capture, continuing with activation of T helper (TH) cells and ending with production of autoantibodies. Activated TH cells differentiate into either TH1 cells, predominately producing proinflammatory cytokines such as interferon , (IFN,) or a TH2 subset mainly producing anti-inflammatory cytokines such as interleukin-4 (IL-4). The aim of the present study was to examine if exposure of autologous nucleus pulposus (NP) to the immune system for 3 weeks is potent enough to prime TH cells to differentiate into TH2 cells. The study was performed in a pig model allowing the exposure of NP to the immune system. To assess the polarization of TH cells the intracellular production of IFN, and IL-4 was measured in T cells by using flow cytometry. The revealed predominant production of IL-4 together with low production of IFN, in T cells after NP exposure to the immune system indicates that nucleus pulposus may prime TH cells to develop into IL-4-producing TH2 cells after being exposed to the immune system, for example, in association with disc herniation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:97,103, 2009 [source] Spasmolytic and antidiarrhoeal properties of the Yucatec Mayan medicinal plant Casimiroa tetrameriaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2005Michael Heinrich The Maya of the Yucatán peninsula commonly use the leaves of Casimiroa tetrameria for treating gastrointestinal disorders, notably diarrhoea and dysentery, as well as gastrointestinal cramps. The phytochemical investigation resulted in the isolation of 13 compounds: eight polymethoxylated flavonoids (two as minor components with a main constituent), four flavonoid glycosides and one furanocoumarin. In this study we used two well-established models in order to assess the gastrointestinal effects of C. tetrameria extracts and isolated compounds: the USSING-chamber, a pharmacological model for diarrhoea, and the isolated guinea pig ileum, a model for modulatory effects on ileum contraction. Extracts and the class of polymethoxylated flavonoids showed strong inhibitory effects in both models, which provides ex-vivo evidence for the use of this botanical drug in the treatment of several gastrointestinal problems, most notably diarrhoea. The crude extract, polymethoxylated flavonoid-rich fractions and the polymethoxylated flavonoids tested showed prominent antisecretory activity. Polymethoxylated flavonoid-rich fractions also inhibited the histamine-induced contractions in the guinea pig model. The effects are not due to a single compound, but to a large number of structurally related compounds that all contribute to the effect. [source] Impaired Terminal Differentiation of Pulmonary Macrophages in a Guinea Pig Model of Chronic Ethanol IngestionALCOHOLISM, Issue 10 2009Sheena D. Brown Background:, Alcoholic patients have an increased risk of respiratory infections, which is partially due to an impaired immune response of alveolar macrophages. The mechanisms by which alcohol impairs alveolar macrophage function are poorly understood. In this study, we demonstrated in a guinea pig model that chronic ethanol ingestion significantly impaired alveolar macrophage differentiation and function. Methods:, Isolated alveolar macrophages were separated into 4 different subpopulations with varying densities and levels of maturation. Results: Compared to control values, chronic ethanol ingestion decreased the percentage of alveolar macrophages in the mature fractions by ,60%. Alveolar macrophage function in each subpopulation was determined by measuring phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus aureus. Alveolar macrophages from ethanol-fed animals had ,80% decrease in the phagocytic index. Western blot and immunohistochemical analysis of the differential markers granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor , (GM-CSFR-,), PU.1, CD11c, and CD11b verified that alcoholic macrophages displayed impaired terminal differentiation. While oral supplementation with the glutathione precursor S -adenosyl-methionine (SAM) did not alter the maturational status of control animals, SAM supplementation shifted the distribution of macrophages to more mature fractions, normalized the phagocytic index; as well as normalized expression of CD11c, CD11b, PU.1, and GM-CSFR-,. Chronic ethanol ingestion also impaired the differentiation status of interstitial macrophages which was normalized by SAM supplementation. Conclusion:, This improvement in the maturational status suggested that ethanol-induced oxidant stress is a central feature in impaired terminal differentiation of macrophages in the interstitial and alveolar space. Therefore, strategies targeting pulmonary oxidant stress may restore macrophage differentiation and function even after chronic ethanol ingestion. [source] In Utero Ethanol Exposure Impairs Defenses Against Experimental Group B Streptococcus in the Term Guinea Pig LungALCOHOLISM, Issue 2 2009Theresa W. Gauthier Background:, The effects of fetal alcohol exposure on the risks of neonatal lung injury and infection remain under investigation. The resident alveolar macrophage (AM) is the first line of immune defense against pulmonary infections. In utero ethanol (ETOH) exposure deranges the function of both premature and term guinea pig AM. We hypothesized that fetal ETOH exposure would increase the risk of pulmonary infection in vivo. Methods:, We developed a novel in vivo model of group B Streptococcus (GBS) pneumonia using our established guinea pig model of fetal ETOH exposure. Timed-pregnant guinea pigs were pair fed ±ETOH and some were supplemented with the glutathione (GSH) precursor S -adenosyl-methionine (SAM-e). Term pups were given GBS intratracheally while some were pretreated with inhaled GSH prior to the experimental GBS. Neonatal lung and whole blood were evaluated for GBS while isolated AM were evaluated using fluorescent microscopy for GBS phagocytosis. Results:, Ethanol-exposed pups demonstrated increased lung infection and sepsis while AM phagocytosis of GBS was deficient compared with control. When SAM-e was added to the maternal diet containing ETOH, neonatal lung and systemic infection from GBS was attenuated and AM phagocytosis was improved. Inhaled GSH therapy prior to GBS similarly protected the ETOH-exposed pup from lung and systemic infection. Conclusions:, In utero ETOH exposure impaired the neonatal lung's defense against experimental GBS, while maintaining GSH availability protected the ETOH-exposed lung. This study suggested that fetal alcohol exposure deranges the neonatal lung's defense against bacterial infection, and support further investigations into the potential therapeutic role for exogenous GSH to augment neonatal AM function. [source] Electrolytic ablation is as effective as radiofrequency ablation in the treatment of artificial liver metastases in a pig modelJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008Sebastian Hinz MD Abstract Background The best treatment option for liver metastases is complete surgical resection. Unfortunately, at the time of diagnosis, not all patients are candidates for complete resection. Electrolytic therapy (ECT) is a novel non-thermal method of tissue destruction. We evaluated its safety and effectiveness in comparison with radiofrequency ablation (RFA). Methods Tumor mimics were created by injecting a gel into the pig liver. The volume of the lesions was measured by ultrasound before treatment. The tumor mimics were treated with either RFA or electrolytic ablation. 48 h after treatment the liver was fixed in formalin and subjected to histological examination. Results Histological investigation confirmed that all lesions were completely surrounded by necrosis after treatment with either ECT or RFA. Two different types of necrosis were identified. After RFA the cell membranes disappeared but the nuclei were still intact, whereas after ECT these structures were completely disrupted. After ECT the necrosis was often surrounded by infiltrating lymphocytes. This inflammatory reaction was not apparent after RFA. Conclusion ECT produced predictable and reproducible necrosis in pig livers and was as effective as RFA at destroying a defined target lesion. A local inflammatory reaction after ECT may favour the development of a systemic immune response. Our results indicate that ECT is an alternative treatment option for irresectable liver metastases. J. Surg. Oncol. 2008;98:135,138. © 2008 Wiley-Liss, Inc. [source] Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig modelLIVER TRANSPLANTATION, Issue 5 2002Grzegorz Nowak MD Microdialysis provides the opportunity to continuously monitor metabolic changes in tissue. The aim of the study is to monitor metabolic changes in the liver graft over time during transplantation in a pig model. Fourteen littermate female pigs with a body weight of 30 to 34 kg were used for seven orthotopic liver transplantations. Intrahepatic implantation of a microdialysis catheter into the liver graft was performed in the donor. Microdialysis samples were collected at 20-minute intervals during the donor operation, cold preservation, and for 7 hours after reperfusion in the recipient. Glucose, lactate, pyruvate, and glycerol concentrations were measured. After cold perfusion, glucose, lactate, and glycerol levels increased, whereas pyruvate levels decreased rapidly. During cold storage, glucose and glycerol levels increased, whereas lactate levels remained stable and pyruvate levels were undetectable. During implantation of the liver graft, glucose, lactate, and glycerol levels showed an accelerated increase. After portal reperfusion, glucose, lactate, and glycerol levels continued to increase for another 40 to 60 minutes, after which they decreased and finally settled at normal levels. At this time, pyruvate levels increased, with a peak within 2 hours after reperfusion, and then decreased to normal levels. Calculated lactate-pyruvate ratio increased after cold perfusion and remained stable during cold storage. During rewarming, it showed an accelerated increase, but after reperfusion, it decreased rapidly. Rewarming and reperfusion are most harmful to the liver, reflected by an accelerated increase in glucose and glycerol levels and lactate-pyruvate ratio. High intrahepatic glucose levels during ischemia appear to be a liver-specific event, which may represent glycogen degradation in injured hepatocytes. [source] Hypoglycaemic effect of Opuntia lindheimeri Englem. in a diabetic pig modelPHYTOTHERAPY RESEARCH, Issue 1 2003Jamie C. Laurenz Abstract The hypoglycaemic activity of Opuntia lindheimeri Englem. was investigated in non-diabetic (control pigs) and streptozotocin-induced diabetic pigs using an enteral (oral) route of administration. Following the administration of O. lindheimeri extract (0, 250 or 500,mg/kg body weight), blood glucose concentrations in control pigs fluctuated around initial baseline concentrations, but were not consistently affected by either the dose of O. lindheimeri or by the time following administration. In contrast, administration of O. lindheimeri extract to STZ-treated pigs resulted in both a dose- (p,<,0.001) and time-dependent (p,<,0.001) decrease in blood glucose concentrations. The hypoglycaemic effect of the extract was apparent within 1,h of administration, with maximal effects occurring at 4,h after administration. These results confirm the hypoglycaemic effect of O. lindheimeri extract in a diabetic pig model. In addition, given the physiological similarities of the pig to humans, this model will be of tremendous use in assessing the long-term effects of Opuntia administration on the secondary problems associated with diabetes. Copyright © 2003 John Wiley & Sons, Ltd. [source] Internal Kinematics of the Tongue Following Volume ReductionTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2008Volodymyr Shcherbatyy Abstract This study was undertaken to determine the functional consequences following tongue volume reduction on tongue internal kinematics during mastication and neuromuscular stimulation in a pig model. Six ultrasonic-crystals were implanted into the tongue body in a wedge-shaped configuration which allows recording distance changes in the bilateral length (LENG) and posterior thickness (THICK), as well as anterior (AW), posterior dorsal (PDW), and ventral (PVW) widths in 12 Yucatan-minipigs. Six animals received a uniform mid-sagittal tongue volume reduction surgery (reduction), and the other six had identical incisions without tissue removal (sham). The initial-distances among each crystal-pairs were recorded before, and immediately after surgery to calculate the dimensional losses. Referring to the initial-distance there were 3,66% and 1,4% tongue dimensional losses by the reduction and sham surgeries, respectively. The largest deformation in sham animals during mastication was in AW, significantly larger than LENG, PDW, PVW, and THICK (P < 0.01,0.001). In reduction animals, however, these deformational changes significantly diminished and enhanced in the anterior and posterior tongue, respectively (P < 0.05,0.001). In both groups, neuromuscular stimulation produced deformational ranges that were 2,4 times smaller than those occurred during chewing. Furthermore, reduction animals showed significantly decreased ranges of deformation in PVW, LENG, and THICK (P < 0.05,0.01). These results indicate that tongue volume reduction alters the tongue internal kinematics, and the dimensional losses in the anterior tongue caused by volume reduction can be compensated by increased deformations in the posterior tongue during mastication. This compensatory effect, however, diminishes during stimulation of the hypoglossal nerve and individual tongue muscles. Anat Rec, 291:886-893, 2008. © 2008 Wiley-Liss, Inc. [source] AM-111 prevents hearing loss from semicircular canal injury in otitis media,THE LARYNGOSCOPE, Issue 1 2010Tyler C. Grindal MD Abstract Objectives/Hypothesis: Iatrogenic semicircular canal (SC) transection during mastoidectomy for chronic otitis media often leads to profound hearing loss. AM-111, an apoptosis inhibitor, has been shown to mitigate hearing loss resulting from a variety of inner ear injuries. The goal of this study was to determine if round window application of AM-111 following SC transection in the presence of Pseudomonas aeruginosa otitis media (PA-OM) may reduce the associated hearing loss. Study Design: Prospective, randomized, controlled study in an animal model. Methods: PA-OM was induced bilaterally in 34 guinea pigs. After 3 days, both bullae were opened and the lateral SC of one ear was transected. AM-111 or vehicle was applied topically to the round window of the ear that had undergone SC transection. Hearing was assessed with auditory brainstem responses. Results: The mean change in hearing thresholds was significantly less in transected ears treated with AM-111 than those receiving vehicle alone when testing with clicks (22.1 dB vs. 35.0 dB; P = .019) and at 4kHz (11.3 dB vs. 40.0 dB; P = .021). A similar trend was shown with 16 kHz tone pips (27.7 dB vs. 41.1 dB; P = .119). Conclusions: AM-111 prevents hearing loss from SC transection in the guinea pig model of PA-OM. Laryngoscope, 2010 [source] Diameter of the Cochlear Nerve in Endolymphatic Hydrops: Implications for the Etiology of Hearing Loss in Ménière's Disease,THE LARYNGOSCOPE, Issue 9 2005Cliff A. Megerian MD Abstract Objective/Hypothesis: Endolymphatic hydrops (ELH) is an important histopathological hallmark of Ménière's disease. Experimental data from human temporal bones as well as animal models of the disorder have generally failed to determine the mechanism by which ELH or related pathology causes hearing loss. Hair cell and spiral ganglion cell counts in both human and animal case studies have not, for the most part, shown severe enough deterioration to explain associated severe sensorineural hearing loss. However a limited number of detailed ultrastructural studies have demonstrated significant reductions in dendritic innervation densities, raising the possibility that neurotoxicity plays an important role in the pathology of Ménière's disease (MD) as well as experimental endolymphatic hydrops (ELH). This study tests the hypothesis that neurotoxicity is an important primary mediator of injury to the hydropic ear and is reflected in measurable deterioration of the cochlear nerve in the animal model of ELH. This study also explores the previously presented hypothesis that cochlear injury in ELH is mediated through the actions of nitric oxide (NO) by evaluating whether hearing loss or various measures of cochlear damage can be ameliorated by administration of an agent that limits excess production of NO. Study Design: Part one of the project involves the surgical induction of endolymphatic hydrops and correlation of long term hearing loss with histological parameters of ELH severity as well as cochlear nerve and eighth cranial nerve diameter measurements. In part two, aminoguanidine is administered orally to a separate set of hydropic animals in an attempt to limit cochlear injury presumably mediated by NO. Methods: Guinea pigs are subjected to surgical induction of unilateral endolymphatic hydrops after establishing baseline ABR thresholds at 2, 4, 8, 16, and 32 kHz. Threshold shifts are established prior to sacrifice at 4 to 6 months and temporal bones processed for light microscopy. Measurements of cochlear nerve and eighth cranial nerve maximal diameters as well as average maximal diameters are carried out and correlated to hearing loss and a semi-quantitative measure of hydrops severity. The identical experiments are carried out in animals treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase. Results: The mean maximal diameter (n = 14) of the hydropic cochlear nerve was significantly reduced (432.14 ± 43.18 vs. 479.28 ± 49.22 microns, P = .0025) as compared to the control nerve. This was also seen in measures of the eighth cranial nerve (855.71 ± 108.82 vs. 929 ± 81.53 microns, P = 0.0003). Correlation studies failed to show correlation between hydrops severity and a cochlear nerve deterioration index (r = -0.0614, P = .8348). Similarly, hearing loss severity failed to correlate with cochlear nerve deterioration (r = 0.1300, P = .6577). There was a significant correlation between hearing loss and hydrops severity (r = 0.6148, P = .0193). Aminoguanidine treated animals (n = 5) also sustained nerve deterioration to the same degree as non-treated animals and there appeared to be no protective effect (at the dosage administered) against ELH related hearing loss, hydrops formation, or nerve deterioration. Conclusion: ELH results in significant deterioration of cochlear nerve and eighth cranial nerve maximal diameters in the guinea pig model. These findings are in accord with previous studies which detected ultrastructural evidence of dendritic damage and indicate that neural injury is of sufficient severity to result in light microscopic evidence of cochlear nerve and eighth cranial nerve deterioration. These data support the concept that the principle pathological insult in ELH is a form of neurotoxicity, especially in light of previous studies which indicate relative preservation of hair cells at similar points in time. The lack of correlation between the severity of hydrops and nerve deterioration suggests that nerve deterioration is independent of hydrops severity. [source] Selective Vestibular Ablation by KTP Laser in Endolymphatic Hydrops,,THE LARYNGOSCOPE, Issue 6 2001Melanie Adamczyk MD Abstract Objectives and Hypothesis Vertigo, the cause of disability in many patients with Ménière's disease, may be the result of the effects of endolymphatic hydrops on the semicircular canals. We hypothesize that intractable vertigo may be controlled by destruction of the semicircular canal neuroepithelium using visible light lasers without the need for extensive fenestration of the bony labyrinth. This study was designed to assess the cochlear effects of potassium titanyl phosphate (KTP) laser-assisted triple semicircular canal ablation (TSCA) in endolymphatic hydrops. Study Design Randomized, prospective, and controlled. Methods Forty-one adult guinea pigs underwent either a unilateral endolymphatic duct occlusion to induce hydrops or a sham procedure. Ten weeks after induction of the hydrops, a KTP laser-assisted TSCA or a sham surgery was performed. Results Electrocochleographic thresholds to clicks and tone-bursts (2,20 kHz) did not change significantly up to 4 weeks after TSCA in hydropic ears. Cross-sectional histology confirmed the presence of hydrops and the ablation of the semicircular canals. Cochlear whole-mounts for hair cell counts showed no significant loss of outer or inner hair cells in hydropic ears treated with TSCA. Conclusion KTP laser-assisted TSCA can be performed in the guinea pig model of endolymphatic hydrops without significant loss of hearing. Evaluation of this technique may be warranted in patients with intractable Ménière's disease. [source] In Vivo Preclinical Anticoagulation Regimens After Implantation of Ventricular Assist DevicesARTIFICIAL ORGANS, Issue 7 2009Diyar Saeed Abstract Ventricular assist devices (VADs) have demonstrated successfully their ability to treat failing circulation of patients with end-stage heart failure. Among the main obstacles with these VADs is thromboembolic events that increase device-related morbidity and mortality. Prior to the clinical application of any newly developed VAD, the feasibility of the device is tested on animal models. Animal species have different hemostatic properties than human patients, and this factor creates a margin of error when comparing the occurrence of VAD-induced thrombosis in an animal versus a human. This detailed literature review provides a thorough documentation of various preclinical anticoagulation protocols used to date, including their outcomes and recommendations for future anticoagulation management strategies. In summary, the outcomes favor a sheep or pig model over other animal models, and discourage the application of a single anticoagulative agent to improve outcomes with any of the currently available devices. [source] In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pigBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2009Masafumi Horie Abstract To evaluate the pharmacokinetics of topical drugs, in vitro permeation studies are performed using sacrificed pig skin or human tissues resected at surgery; however, these methods have their limitations in in vivo pharmacokinetics. This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24,h, followed by sequential collection of blood specimens from 0 to 36,h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12,h after the application (n=4). Ketoprofen was first detected in the plasma at 8,h, the concentration increasing up to 24,h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprofen concentrations in the tissues decreased with increasing depth of the tissues, but the values in the deep muscles, being the lowest among the tissues examined, were still higher than those in the plasma. While the data of drug concentration in human tissue are difficult to test, the Mexican hairless pig model appears to be attractive for in vivo pharmacokinetic studies of topically applied ketoprofen. Copyright © 2009 John Wiley & Sons, Ltd. [source] Single-port, single-operator-light endoscopic robot-assisted laparoscopic urology: pilot study in a pig modelBJU INTERNATIONAL, Issue 5 2010Sebastien Crouzet Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVES To present our initial operative experience in which single-port-light endoscopic robot-assisted reconstructive and extirpative urological surgery was performed by one surgeon, using a pig model. MATERIALS AND METHODS This pilot study was conducted in male farm pigs to determine the feasibility and safety of single-port, single-surgeon urological surgery. All pigs had a general anaesthetic and were placed in the flank position. A 2-cm umbilical incision was made, through which a single port was placed and pneumoperitoneum obtained. An operative laparoscope was introduced and securely held using a novel low-profile robot under foot and/or voice control. Using articulating instruments, each pig had bilateral reconstructive and extirpative renal surgery. Salient intraoperative and postmortem data were recorded. Results were analysed statistically to determine if outcomes improved with surgeon experience. RESULTS Five male farm pigs underwent bilateral partial nephrectomy and bilateral pyeloplasty before a completion bilateral radical nephrectomy. There were no intraoperative complications and there was no need for additional ports to be placed. The mean (range) operative duration for partial nephrectomy, pyeloplasty, and nephrectomy were 120,(100,150), 110,(95,130) and 20,(15,30),min, respectively. The mean (range) estimated blood loss for all procedures was 240,(200,280),mL. The preparation time decreased with increasing number of cases (P = 0.002). CONCLUSIONS The combination of a single-port, a robotic endoscope holder and articulated instruments operated by one surgeon is feasible. With a single-port access, the robot allows more room to the surgeon than an assistant. [source] Modified ureterosigmoidostomy (Mainz Pouch II): a nonrefluxing stented vs unstented laparoscopic porcine modelBJU INTERNATIONAL, Issue 2 2008Mitchell R. Humphreys OBJECTIVE To describe a rapid and reproducible pure laparoscopic cystectomy and nonrefluxing modified continent urinary diversion (Mainz Pouch II), and to determine whether ureteric stenting decreases ureteric obstruction after surgery. MATERIALS AND METHODS After institutional review and approval, six female pigs (51,55 kg) had a laparoscopic cystectomy and urinary diversion using a modified Mainz Pouch II. Imbricating bowel over the extra-intestinal ureteric segment created the nonrefluxing mechanism. All pigs had the same bowel preparation before a standard four-port transperitoneal laparoscopic procedure, but three pigs received bilateral J ureteric stents and three did not. Body weights, radiographic imaging, serum electrolytes and renal function were monitored during the 6-week survival period. RESULTS One stented pig developed bilateral pyelonephritis, renal obstruction and was killed. Including this pig, four of 12 renal units were obstructed, occurring more often in the stented pigs. There were no significant differences between the serum electrolytes before and after surgery or between the stented or unstented pigs. The surgery was quicker as experience increased. No pig developed hyperchloraemic metabolic acidosis. The nonrefluxing modification appeared to be effective, as reflux was only present in one renal unit. CONCLUSIONS Laparoscopic ureterosigmoidostomy, specifically the modified Mainz Pouch II, represents a viable and reasonable continent urinary diversion. The results suggest that there was no benefit in stenting in this pig model. [source] | ||||||||||||||||||||||||||||