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Sample records for rabbit elastase-induced model

  1. A New Flow-Diverter (the FloWise): In-Vivo Evaluation in an Elastase-Induced Rabbit Aneurysm Model

    PubMed Central

    Kim, Dong Joon; Kim, Dong Ik

    2016-01-01

    Objective We aimed to evaluate the efficacy and safety of a newly developed, partially retrievable flow-diverter (the FloWise) in an elastase-induced rabbit aneurysm model. Materials and Methods We developed a partially retrievable flow diverter composed of 48 strands of Nitinol and platinum wire. The FloWise is compatible with any microcatheter of 0.027-inch inner diameter, and is retrievable up to 70% deployment. The efficacy and safety of the FloWise were evaluated in the elastase-induced rabbit aneurysm model. The rate of technical success (full coverage of aneurysm neck) and assessment of aneurysm occlusion and stent patency was conducted by angiograms and histologic examinations at the 1-month, 3-month, and 6-month follow-up. The patency of small arterial branches (intercostal or lumbar arteries) covered by the FloWise were also assessed in the 5 subjects. Results We attempted FloWise insertion in a total of 32 aneurysm models. FloWise placement was successful in 31 subjects (96.9%). Two stents (6.2%) were occluded at the 3-month follow-up, but there was no evidence of in-stent stenosis in other subjects. All stented aneurysms showed progressive occlusion: grade I (complete aneurysm occlusion) in 44.4% and grade II (aneurysm occlusion > 90%) in 55.6% at 1 month; grade I in 90% and II in 10% at 3 months; and grade I in 90% and II in 10% at 6 months. All small arterial branches covered by the FloWise remained patent. Conclusion A newly developed, partially retrievable flow-diverter seems to be a safe and effective tool of aneurysm occlusion, as evaluated in the rabbit aneurysm model. PMID:26798228

  2. Experimental testing of the dual-layer Woven EndoBridge device using an elastase-induced aneurysm model in rabbits.

    PubMed

    Ding, Yong-Hong; Dai, Daying; Schroeder, Dana; Kadirvel, Ramanathan; Kallmes, David F

    2016-06-01

    The dual-layer Woven EndoBridge (WEB) device (WEB II) is designed to improve the performance of the first-generation WEB device. This study was performed to evaluate the acute and chronic performance of WEB II for aneurysm occlusion in an elastase-induced aneurysm model in rabbits. We implanted WEB II devices in 36 elastase-induced aneurysms and followed up for one, three, six, and 12 months. Degree of aneurysm occlusion at follow-up was graded on the Web Occlusion Scale (WOS): Grade A, complete aneurysm occlusion; Grade B, complete occlusion with recess filling; Grade C, residual neck filling; and Grade D, residual aneurysm filling. Hematoxylin and eosin staining was performed for histological assessment of aneurysm healing. Grades A, B, C, and D aneurysm occlusion at one-month follow-up were noted in three (17%), three (17%), eight (44%), and four (22%) of 18 cases, respectively. At the three-month time point Grades A, B, C, and D were shown in two (33%), two (33%), one (17%), and one (17%) aneurysms. Six months after treatment, one (17%), two (33%), two (33%), and one (17%) cases demonstrated Grades A, B, C, and D occlusion. At the 12-month time point, Grades B, C, and D were shown in three (50%), two (33%), and one (17%) aneurysms. Histologic evaluation showed progressive thrombus organization within aneurysm lumen from one to 12 months. These results indicated that the WEB II device can achieve high rates of aneurysm occlusion over time in experimental aneurysms. PMID:26847799

  3. Elastase-induced pulmonary emphysema: insights from experimental models.

    PubMed

    Antunes, Mariana A; Rocco, Patricia R M

    2011-12-01

    Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema. PMID:22159348

  4. Bronchial responsiveness in an elastase-induced mouse model of emphysema.

    PubMed

    Santos, Luiz Marcelo Oliveira; de Brito Cervilha, Daniela Aparecida; Cabral, Layla Dutra Marinho; Garcia, Érika Kristina Incerpi; Teixeira, Vanessa Pereira; Brito, Jôse Mára; Moriya, Henrique Takachi; Soncini, Roseli

    2014-04-01

    Bronchial responsiveness during methacholine (MCh) challenge was analysed in an elastase-induced mouse model of emphysema to explore the magnitude of the response in this model. Swiss mice were intratracheally instilled with saline or elastase (0.3 or 0.6 U). Twenty days afterward, mechanical ventilation data were collected from the closed and opened thorax of baseline and MCh (vehicle, 50 and 100 mg/mL) challenged mice. The lungs were prepared for morphometric analysis. In the 0.6 U group, airway resistance (Raw) and tissue elastance (H) were decreased, and hysteresivity (η) was increased (closed thorax). MCh increased Raw, G and H in all groups, but this increase was attenuated in the elastase-induced emphysema groups, the largest attenuation was observed in the 0.6 U (closed thorax condition). Elastase increased hyperinflation of the alveoli, alveolar collapse and the Lm and reduced the normal area. MCh reduced respiratory mechanics in elastase-induced emphysema, and this reduction was modulated by the collapsed and/or hyperinflated areas, which increased the heterogeneity of the lungs. PMID:24463010

  5. Therapeutic effects of LASSBio-596 in an elastase-induced mouse model of emphysema

    PubMed Central

    Padilha, Gisele A.; Henriques, Isabela; Lopes-Pacheco, Miquéias; Abreu, Soraia C.; Oliveira, Milena V.; Morales, Marcelo M.; Lima, Lidia M.; Barreiro, Eliezer J.; Silva, Pedro L.; Xisto, Debora G.; Rocco, Patricia R. M.

    2015-01-01

    Emphysema is an intractable pulmonary disease characterized by an inflammatory process of the airways and lung parenchyma and ongoing remodeling process in an attempt to restore lung structure. There is no effective drug therapy that regenerates lung tissue or prevents the progression of emphysema; current treatment is aimed at symptomatic relief. We hypothesized that LASSBio-596, a molecule with potent anti-inflammatory and immunomodulatory effects, might reduce pulmonary inflammation and remodeling and thus improve lung function in experimental emphysema. Emphysema was induced in BALB/c mice by intratracheal administration of porcine pancreatic elastase (0.1 IU) once weekly during 4 weeks. A control group received saline using the same protocol. After the last instillation of saline or elastase, dimethyl sulfoxide, or LASSBio-596 were administered intraperitoneally, once daily for 8 days. After 24 h, in elastase-induced emphysema animals, LASSBio-596 yielded: (1) decreased mean linear intercept, hyperinflation and collagen fiber content, (2) increased elastic fiber content, (3) reduced number of M1 macrophages, (4) decreased tumor necrosis factor-α, interleukin-1β, interleukin-6, and transforming growth factor-β protein levels in lung tissue, and increased vascular endothelial growth factor. These changes resulted in increased static lung elastance. In conclusion, LASSBio-596 therapy reduced lung inflammation, airspace enlargement, and small airway wall remodeling, thus improving lung function, in this animal model of elastase-induced emphysema. PMID:26483698

  6. Therapeutic effects of LASSBio-596 in an elastase-induced mouse model of emphysema.

    PubMed

    Padilha, Gisele A; Henriques, Isabela; Lopes-Pacheco, Miquéias; Abreu, Soraia C; Oliveira, Milena V; Morales, Marcelo M; Lima, Lidia M; Barreiro, Eliezer J; Silva, Pedro L; Xisto, Debora G; Rocco, Patricia R M

    2015-01-01

    Emphysema is an intractable pulmonary disease characterized by an inflammatory process of the airways and lung parenchyma and ongoing remodeling process in an attempt to restore lung structure. There is no effective drug therapy that regenerates lung tissue or prevents the progression of emphysema; current treatment is aimed at symptomatic relief. We hypothesized that LASSBio-596, a molecule with potent anti-inflammatory and immunomodulatory effects, might reduce pulmonary inflammation and remodeling and thus improve lung function in experimental emphysema. Emphysema was induced in BALB/c mice by intratracheal administration of porcine pancreatic elastase (0.1 IU) once weekly during 4 weeks. A control group received saline using the same protocol. After the last instillation of saline or elastase, dimethyl sulfoxide, or LASSBio-596 were administered intraperitoneally, once daily for 8 days. After 24 h, in elastase-induced emphysema animals, LASSBio-596 yielded: (1) decreased mean linear intercept, hyperinflation and collagen fiber content, (2) increased elastic fiber content, (3) reduced number of M1 macrophages, (4) decreased tumor necrosis factor-α, interleukin-1β, interleukin-6, and transforming growth factor-β protein levels in lung tissue, and increased vascular endothelial growth factor. These changes resulted in increased static lung elastance. In conclusion, LASSBio-596 therapy reduced lung inflammation, airspace enlargement, and small airway wall remodeling, thus improving lung function, in this animal model of elastase-induced emphysema. PMID:26483698

  7. Tracking Intravenous Adipose-Derived Mesenchymal Stem Cells in a Model of Elastase-Induced Emphysema

    PubMed Central

    Kim, You-Sun; Kim, Ji-Young; Shin, Dong-Myung; Huh, Jin Won; Lee, Sei Won

    2014-01-01

    Background Mesenchymal stem cells (MSCs) obtained from bone marrow or adipose tissue can successfully repair emphysematous animal lungs, which is a characteristic of chronic obstructive pulmonary disease. Here, we describe the cellular distribution of MSCs that were intravenously injected into mice with elastase-induced emphysema. The distributions were also compared to the distributions in control mice without emphysema. Methods We used fluorescence optical imaging with quantum dots (QDs) to track intravenously injected MSCs. In addition, we used a human Alu sequence-based real-time polymerase chain reaction method to assess the lungs, liver, kidney, and spleen in mice with elastase-induced emphysema and control mice at 1, 4, 24, 72, and 168 hours after MSCs injection. Results The injected MSCs were detected with QD fluorescence at 1- and 4-hour postinjection, and the human Alu sequence was detected at 1-, 4- and 24-hour postinjection in control mice (lungs only). Injected MSCs remained more in mice with elastase-induced emphysema at 1, 4, and 24 hours after MSCs injection than the control lungs without emphysema. Conclusion In conclusion, our results show that injected MSCs were observed at 1 and 4 hours post injection and more MSCs remain in lungs with emphysema. PMID:25309606

  8. The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema

    PubMed Central

    Kim, You-Sun; Kim, Ji-Young; Huh, Jin Won; Lee, Sei Won; Choi, Soo Jin

    2015-01-01

    Background Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only 5×104 MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients. PMID:26175778

  9. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model.

    PubMed

    Chen, Young-Bin; Lan, Ying-Wei; Chen, Lih-Geeng; Huang, Tsung-Teng; Choo, Kong-Bung; Cheng, Winston T K; Lee, Hsuan-Shu; Chong, Kowit-Yu

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease. Here, this same stem cell line was evaluated for its protective capacity to alleviate elastase-induced pulmonary emphysema in mice. Results of this study showed that c-RSV-treatment of HSP-VEGFA-MSC exhibited synergy between HSP70 transcription activity and induced expression of anti-oxidant-related genes when challenged by cigarette smoke extracts. Eight weeks after jugular vein injection of HSP-VEGFA-MSC into mice with elastase-induced pulmonary emphysema followed by c-RSV treatment to induce transgene expression, significant improvement was observed in respiratory functions. Expression of VEGFA, endogenous nuclear factor erythroid 2-related factor (Nrf 2), and manganese superoxide dismutase (MnSOD) was significantly increased in the lung tissues of the c-RSV-treated mice. Histopathologic examination of treated mice revealed gradual but significant abatement of emphysema and restoration of airspace volume. In conclusion, the present investigation demonstrates that c-RSV-regulated VEGFA expression in HSP-VEGFA-MSC significantly improved the therapeutic effects on the treatment of COPD in the mouse, possibly avoiding side effects associated with constitutive VEGFA expression. PMID:26243699

  10. Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

    PubMed

    Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

    2016-01-01

    Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema. PMID:27150147

  11. DOSE RESPONSE OF ELASTASE-INDUCED EMPHYSEMA IN HAMSTERS

    EPA Science Inventory

    Elastase-induced emhysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. It appears that as little as 6 units of elastase produces mild emphysema in hamste...

  12. Sensitivity of CFD based hemodynamic results in rabbit aneurysm models to idealizations in surrounding vasculature.

    PubMed

    Zeng, Zijing; Kallmes, David F; Durka, Michael J; Ding, Yonghong; Lewis, Debra; Kadirvel, Ramanathan; Robertson, Anne M

    2010-09-01

    Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating the role of hemodynamics in vascular diseases such as cerebral aneurysms and atherosclerosis. However, such models necessarily only include isolated segments of the vasculature. In this work, we evaluate the influence of geometric approximations in vascular anatomy on hemodynamics in elastase induced saccular aneurysms in rabbits. One representative high aspect ratio (AR-height/neck width) aneurysm and one low AR aneurysm were created at the origin of the right common carotid artery in two New Zealand white rabbits. Three-dimensional (3D) reconstructions of the aneurysm and surrounding arteries were created using 3D rotational angiographic data. Five models with varying extents of neighboring vasculature were created for both the high and low AR cases. A reference model included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies were performed and streamlines, wall shear stress (WSS), oscillatory shear index, and cross sectional velocity were compared between the models. The influence of the vascular domain on intra-aneurysmal hemodynamics varied between the low and high AR cases. For the high AR case, even a simple model including only the aneurysm, a small section of neighboring vasculature, and simple extensions captured the main features of the steamline and WSS distribution predicted by the reference model. However, the WSS distribution in the low AR case was more strongly influenced by the extent of vasculature. In particular, it was necessary to include the downstream quadrification and upstream LCCA to obtain good predictions of WSS. The findings in this work demonstrate the accuracy of CFD results can be compromised if insufficient neighboring vessels are included in studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of aspect ratio, hemodynamic

  13. Sensitivity of CFD Based Hemodynamic Results in Rabbit Aneurysm Models to Idealizations in Surrounding Vasculature

    PubMed Central

    Zeng, Zijing; Kallmes, David F.; Durka, Michael J.; Ding, Yonghong; Lewis, Debra; Kadirvel, Ramanathan

    2010-01-01

    Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating the role of hemodynamics in vascular diseases such as cerebral aneurysms and atherosclerosis. However, such models necessarily only include isolated segments of the vasculature. In this work, we evaluate the influence of geometric approximations in vascular anatomy on hemodynamics in elastase induced saccular aneurysms in rabbits. One representative high aspect ratio (AR—height/neck width) aneurysm and one low AR aneurysm were created at the origin of the right common carotid artery in two New Zealand white rabbits. Three-dimensional (3D) reconstructions of the aneurysm and surrounding arteries were created using 3D rotational angiographic data. Five models with varying extents of neighboring vasculature were created for both the high and low AR cases. A reference model included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies were performed and streamlines, wall shear stress (WSS), oscillatory shear index, and cross sectional velocity were compared between the models. The influence of the vascular domain on intra-aneurysmal hemodynamics varied between the low and high AR cases. For the high AR case, even a simple model including only the aneurysm, a small section of neighboring vasculature, and simple extensions captured the main features of the steamline and WSS distribution predicted by the reference model. However, the WSS distribution in the low AR case was more strongly influenced by the extent of vasculature. In particular, it was necessary to include the downstream quadrification and upstream LCCA to obtain good predictions of WSS. The findings in this work demonstrate the accuracy of CFD results can be compromised if insufficient neighboring vessels are included in studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of aspect ratio, hemodynamic

  14. Lack of Transcription Factor p53 Exacerbates Elastase-Induced Emphysema in Mice.

    PubMed

    Chrusciel, Sandra; Zysman, Maéva; Caramelle, Philippe; Tiendrebeogo, Arnaud; Baskara, Indoumady; Le Gouvello, Sabine; Chabot, François; Giraudier, Stéphane; Boczkowski, Jorge; Boyer, Laurent

    2016-02-01

    The transcription factor p53 is overexpressed in the lung of patients with emphysema, but it remains unclear if it has a deleterious or protective effect in disease progression. We investigated the role of p53 in the elastase-induced emphysema model and the molecular underlining mechanisms. Wild-type (WT) and p53(-/-) mice were instilled with pancreatic porcine elastase. We quantified emphysema (morphometric analysis), chemokine (C-C motif) ligand 2 (CCL2), and TNF-α in bronchoalveolar lavage (BAL) (ELISA), oxidative stress markers [heme oxygenase 1 (HO1), NAD(P)H dehydrogenase quinone 1 (NQO1), and quantitative RT-PCR], matrix metalloproteinase 12 (MMP12) expression, and macrophage apoptosis (cleaved caspase-3, immunofluorescence). p53 gene expression was up-regulated in the lung of elastase-instilled mice. p53 deletion aggravated elastase-induced emphysema severity, pulmonary inflammation (macrophage and neutrophil numbers and CCL2 and TNF-α levels in BAL), and lung oxidative stress. These findings, except for the increase in CCL2, were reproduced in WT mice transplanted with p53(-/-) bone marrow cells. The increased number of macrophages in p53(-/-) mice was not a consequence of reduced apoptosis or an excess of chemotaxis toward CCL2. Macrophage expression of MMP12 was higher in p53(-/-) mice compared with WT mice after elastase instillation. These findings provide evidence that p53(-/-) mice and WT mice grafted with p53(-/-) bone marrow cells are more prone to developing elastase-induced emphysema, supporting a protective role of p53, and more precisely p53 expressed in macrophages, against emphysema development. The pivotal role played by macrophages in this phenomenon may involve the MMP12-TNF-α pathway. PMID:26106979

  15. Moderate Aerobic Training Improves Cardiorespiratory Parameters in Elastase-Induced Emphysema

    PubMed Central

    Henriques, Isabela; Lopes-Pacheco, Miquéias; Padilha, Gisele A.; Marques, Patrícia S.; Magalhães, Raquel F.; Antunes, Mariana A.; Morales, Marcelo M.; Rocha, Nazareth N.; Silva, Pedro L.; Xisto, Débora G.; Rocco, Patricia R. M.

    2016-01-01

    Aim: We investigated the therapeutic effects of aerobic training on lung mechanics, inflammation, morphometry and biological markers associated with inflammation, and endothelial cell damage, as well as cardiac function in a model of elastase-induced emphysema. Methods: Eighty-four BALB/c mice were randomly allocated to receive saline (control, C) or 0.1 IU porcine pancreatic elastase (emphysema, ELA) intratracheally once weekly for 4 weeks. After the end of administration period, once cardiorespiratory impairment associated with emphysema was confirmed, each group was further randomized into sedentary (S) and trained (T) subgroups. Trained mice ran on a motorized treadmill, at moderate intensity, 30 min/day, 3 times/week for 4 weeks. Results: Four weeks after the first instillation, ELA animals, compared to C, showed: (1) reduced static lung elastance (Est,L) and levels of vascular endothelial growth factor (VEGF) in lung tissue, (2) increased elastic and collagen fiber content, dynamic elastance (E, in vitro), alveolar hyperinflation, and levels of interleukin-1β and tumor necrosis factor (TNF)-α, and (3) increased right ventricular diastolic area (RVA). Four weeks after aerobic training, ELA-T group, compared to ELA-S, was associated with reduced lung hyperinflation, elastic and collagen fiber content, TNF-α levels, and RVA, as well as increased Est,L, E, and levels of VEGF. Conclusion: Four weeks of regular and moderate intensity aerobic training modulated lung inflammation and remodeling, thus improving pulmonary function, and reduced RVA and pulmonary arterial hypertension in this animal model of elastase-induced emphysema. PMID:27536247

  16. Analysis of Hemodynamics and Aneurysm Occlusion after Flow Diverting Treatment in Rabbit Models

    PubMed Central

    Cebral, Juan R.; Mut, Fernando; Raschi, Marcelo; Hodis, Simona; Ding, Yong-Hong; Erickson, Bradley J.; Kadirvel, Ramanathan; Kallmes, David F.

    2015-01-01

    Purpose to investigate the relationship between hemodynamic conditions created immediately after flow diversion and subsequent occlusion of experimental aneurysms in rabbits. Methods The hemodynamic environment before and after flow diversion treatment of elastase induced aneurysms in 20 rabbits was modeled using image-based computational fluid dynamics. Local aneurysm occlusion was quantified using a voxelization technique on 3D images acquired 8 weeks after treatment. Global and local voxel-by-voxel hemodynamic variables were used to statistically compare aneurysm regions that later thrombosed to regions that remained patent. Results Six aneurysms remained patent at 8 weeks while 14 were completely or nearly completely occluded. Patent aneurysms had statistically larger neck sizes (p=0.0015) and smaller mean transit times (p=0.02). The velocity, vorticity and shear rate were about 2.8 times (p<0.0001) larger in patent regions, i.e. had larger “flow activity”, than regions that progressed to occlusion. Statistical models based on local hemodynamic variables were capable of predicting local occlusion with good precision (84% accuracy), especially away from the neck (92–94%). Predictions near the neck were poorer (73% accuracy). Conclusion These results suggests that the dominant healing mechanism of occlusion within the aneurysm dome are related to slow flow induced thrombosis while near the neck other processes could be at play simultaneously. PMID:24729467

  17. Analysis of Hemodynamics and Aneurysm Occlusion after Flow Diverting Treatment in Rabbit Models

    PubMed Central

    Cebral, Juan R.; Mut, Fernando; Raschi, Marcelo; Hodis, Simona; Ding, Yong-Hong; Erickson, Bradley J.; Kadirvel, Ramanathan; Kallmes, David F.

    2014-01-01

    Purpose to investigate the relationship between hemodynamic conditions created immediately after flow diversion and subsequent occlusion of experimental aneurysms in rabbits. Methods The hemodynamic environment before and after flow diversion treatment of elastase induced aneurysms in 20 rabbits was modeled using image-based computational fluid dynamics. Local aneurysm occlusion was quantified using a voxelization technique on 3D images acquired 8 weeks after treatment. Global and local voxel-by-voxel hemodynamic variables were used to statistically compare aneurysm regions that later thrombosed to regions that remained patent. Results Six aneurysms remained patent at 8 weeks while 14 were completely or nearly completely occluded. Patent aneurysms had statistically larger neck sizes (p=0.0015) and smaller mean transit times (p=0.02). The velocity, vorticity and shear rate were about 2.8 times (p<0.0001) larger in patent regions, i.e. had larger “flow activity”, than regions that progressed to occlusion. Statistical models based on local hemodynamic variables were capable of predicting local occlusion with good precision (84% accuracy), especially away from the neck (92–94%). Predictions near the neck were poorer (73% accuracy). Conclusion These results suggests that the dominant healing mechanism of occlusion within the aneurysm dome are related to slow flow induced thrombosis while near the neck other processes could be at play simultaneously. PMID:24722302

  18. Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

    PubMed

    Quintana, Harry Karmouty; Cannet, Catherine; Zurbruegg, Stefan; Blé, François-Xavier; Fozard, John R; Page, Clive P; Beckmann, Nicolau

    2006-12-01

    Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases. PMID:17029230

  19. Rabbit model of rotavirus infection.

    PubMed Central

    Conner, M E; Estes, M K; Graham, D Y

    1988-01-01

    A new small animal model was developed to study parameters of rotavirus infections, including the active immune response. Seronegative New Zealand White rabbits (neonatal to 4 months old) were inoculated orally with cultivatable rabbit rotavirus strains Ala, C11, and R2 and with the heterologous simian strain SA11. The course of infection was evaluated by clinical findings, virus isolation (plaque assay and enzyme-linked immunosorbent assay), and serologic response. All four strains of virus were capable of infecting rabbits as determined by isolation of infectious virus from intestinal contents or fecal samples, by seroconversion, or by a combination of these methods. The responses differed depending on the virus strain used for inoculation. Rabbits remained susceptible to primary infection to at least 16 weeks of age (upper limit examined). Virus excretion in intestinal contents was detected from 6 h to 7 days postinoculation. RNA electropherotypes of inocula and viruses isolated from rabbits were the same in all samples tested. Transmission of Ala virus and R2 virus but not SA11 virus from inoculated animals to uninoculated controls also occurred. In a challenge experiment with Ala virus, 74- and 90-day-old rabbits were rechallenged with Ala 5 weeks after a primary infection with Ala. Virus was excreted in feces from 2 to 8 days after the primary infection but was not excreted after challenge. These results indicate that the rabbit provides an ideal model to investigate both the primary and secondary active immune responses to rotavirus infections and to evaluate candidate vaccines. Images PMID:2833612

  20. Keratinocyte growth factor protects against elastase-induced pulmonary emphysema in mice.

    PubMed

    Plantier, Laurent; Marchand-Adam, Sylvain; Antico Arciuch, Valeria G; Antico, Valeria G; Boyer, Laurent; De Coster, Cécile; Marchal, Joëlle; Bachoual, Rafik; Mailleux, Arnaud; Boczkowski, Jorge; Crestani, Bruno

    2007-11-01

    Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The keratinocyte growth factor (KGF) favorably influences alveolar maintenance and repair and possesses anti-inflammatory properties. We aimed to determine whether exogenous KGF prevented or corrected elastase-induced pulmonary emphysema in vivo. Treatment with 5 mg x kg(-1) x day(-1) KGF before elastase instillation prevented pulmonary emphysema. This effect was associated with 1) a sharp reduction in bronchoalveolar lavage fluid total protein and inflammatory cell recruitment, 2) a reduction in the pulmonary expression of the chemokines CCL2 (or monocyte chemoattractant protein-1) and CXCL2 (or macrophage inflammatory protein-2alpha) and of the adhesion molecules ICAM-1 and VCAM-1, 3) a reduction in matrix metalloproteinase (MMP)-2 and MMP-9 activity at day 3, and 4) a major reduction in DNA damage detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) in alveolar cells at day 7. Treatment with KGF after elastase instillation had no effect on elastase-induced emphysema despite the conserved expression of the KGF receptor in the lungs of elastase-instilled animals as determined by immunohistochemistry. In vitro, KGF abolished the elastase-induced increase in CCL2, CXCL2, and ICAM-1 mRNA in the MLE-12 murine alveolar epithelial cell line. We conclude that KGF pretreatment protected against elastase-induced pulmonary inflammation, activation of MMPs, alveolar cell DNA damage, and subsequent emphysema in mice. PMID:17766584

  1. Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

    PubMed Central

    Suzuki, Tomoko; Yamashita, Cory; Zemans, Rachel L.; Briones, Natalie; Van Linden, Annemie; Downey, Gregory P.

    2009-01-01

    Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-κB, and the protooncogene p53 in this pathway. Elastase-induced apoptosis of lung epithelial cells correlated temporally with activation of NF-κB, phosphorylation, and nuclear translocation of p53, increased p53 up-regulated modulator of apoptosis (PUMA) expression, and mitochondrial translocation of Bax resulting in enhanced permeability. Elastase-induced apoptosis was also prevented by pharmacologic inhibitors of NF-κB and p53 and by short interfering RNA knockdown of PAR-1, p53, or PUMA. These inhibitors prevented elastase-induced PUMA expression, mitochondrial translocation of Bax, increased mitochondrial permeability, and attenuated apoptosis. NF-κB inhibitors also reduced p53 phosphorylation. We conclude that elastase-induced apoptosis of lung epithelial cells is mediated by a PAR-1–triggered pathway involving activation of NF-κB and p53, and a PUMA- and Bax-dependent increase in mitochondrial permeability leading to activation of distal caspases. Further, p53 contributes to elastase-induced apoptosis by both transcriptional and post-transcriptional mechanisms. PMID:19307610

  2. Rabbit models for continuous curvilinear capsulorhexis instruction

    PubMed Central

    Ruggiero, Jason; Keller, Christopher; Porco, Travis; Naseri, Ayman; Sretavan, David W.

    2012-01-01

    PURPOSE To develop a rabbit model for continuous curvilinear capsulorhexis (CCC) instruction. SETTING University of California San Francisco, San Francisco, California, USA. DESIGN Experimental study. METHODS Isolated rabbit lenses were immersed in 2% to 8% paraformaldehyde (PFA) fixative from 15 minutes to 6 hours. Rabbit eyes were treated by substituting aqueous with 2% to 4% PFA for 30 minutes to 6 hours, followed by washes with a balanced salt solution. Treated lenses and eyes were held in purpose-designed holders using vacuum. A panel of 6 cataract surgeons with 5 to 15 years of experience performed CCC on treated lenses and eyes and responded to a questionnaire regarding the utility of these models for resident teaching using a 5-item Likert scale. RESULTS The expert panel found that rabbit lenses treated with increasing amounts of fixative simulated CCC on human lens capsules from the third to the seventh decade of life. The panel also found fixative-treated rabbit eyes to simulate some of the experience of CCC within the human anterior chamber but noted a shallower anterior chamber depth, variation in pupil size, and corneal clouding under some treatment conditions. CONCLUSIONS Experienced cataract surgeons who performed CCC on these rabbit models strongly agreed that isolated rabbit lenses treated with fixative provide a realistic simulation of CCC in human patients and that both models were useful tools for capsulorhexis instruction. Results indicate that rabbit lenses treated with 8% PFA for 15 minutes is a model with good fidelity for CCC training. PMID:22727296

  3. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  4. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  5. Habitat Suitability Index Models: Swamp Rabbit

    USGS Publications Warehouse

    Allen, Arthur W.

    1985-01-01

    A review and synthesis of existing information were used to develop a Habitat Suitability Index (HSI) model for the swamp rabbit (Sylvilagus aquaticus). The model consolidates habitat use information into a framework appropriate for field application, and is scaled to produce an index between 0.0 (unsuitable habitat) to 1.0 (optimum habitat). HSI models are designed to be used with Habitat Evaluation Procedures previously developed by the U.S. Fish and Wildlife Service.

  6. Effect of low-level NO/sub 2/ chronic exposure on elastase-induced emphysema

    SciTech Connect

    Lafuma, C.; Harf, A.; Lange, F.; Bozzi, L.; Poncy, J.L.; Bignon, J.

    1987-06-01

    The effect of chronic exposure to 2 ppm nitrogen dioxide (NO/sub 2/) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept (Lm) and internal surface area (ISA)), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used: control, NO/sub 2/-exposed, elastase-treated, and NO/sub 2/-exposed postelastase. Results show that NO/sub 2/ exposure alone induced mild emphysematous lesions whose degree of severity was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO/sub 2/ enhanced elastase-induced emphysema. By contrast, study of lung mechanics revealed no difference between the control and NO/sub 2/-exposed groups or between the elastase-treated animals exposed to NO/sub 2/ and those not so exposed. Lastly, results suggest that chronic exposure to 2 ppm NO/sub 2/ may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.

  7. An individual-based model of rabbit viral haemorrhagic disease on European wild rabbits (Oryctolagus cuniculus)

    USGS Publications Warehouse

    Fa, John E.; Sharples, Colin M.; Bell, Diana J.; DeAngelis, Donald L.

    2001-01-01

    We developed an individual-based model of Rabbit Viral Hemorrhagic Disease (RVHD) for European wild rabbits (Oryctolagus cuniculus L.), representing up to 1000 rabbits in four hectares. Model output for productivity and recruitment matched published values. The disease was density-dependent and virulence affected outcome. Strains that caused death after several days produced greater overall mortality than strains in which rabbits either died or recovered very quickly. Disease effect also depended on time of year. We also elaborated a larger scale model representing 25 km2 and 100,000+ rabbits, split into a number of grid-squares. This was a more traditional model that did not represent individual rabbits, but employed a system of dynamic equations for each grid-square. Disease spread depended on probability of transmission between neighboring grid-squares. Potential recovery from a major population crash caused by the disease relied on disease virulence and frequency of recurrence. The model's dependence on probability of disease transmission between grid-squares suggests the way that the model represents the spatial distribution of the population affects simulation. Although data on RVHD in Europe are lacking, our models provide a basis for describing the disease in realistic detail and for assessing influence of various social and spatial factors on spread.

  8. High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

    PubMed

    Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

    2014-10-01

    Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P < 0.001), whereas injection of HDL or AAT alone only showed a moderate, nonsignificant protective effect (28.2 ± 4.2 μm versus 30.7 ± 5 μm [P = 0.23] and 27.3 ± 5.66 μm versus 30.71 ± 4.96 μm [P = 0.18], respectively). Indeed, protection by HDL-AAT was significantly higher than that observed with HDL or AAT (P = 0.006 and P = 0.048, respectively). This protective effect was associated (at 6, 24, and 72 h) with: (1) a reduction in neutrophil and macrophage number in the bronchoalveolar lavage fluid; (2) decreased concentrations of IL-6, monocyte chemoattractant protein-1, and TNF-α in both bronchoalveolar lavage fluid and plasma; (3) a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-9 activities; and (4) a reduction in the degradation of fibronectin, a marker of tissue damage. In addition, HDL-AAT reduced acute cigarette smoke-induced inflammatory response. Intravenous HDL-AAT treatment afforded a better protection against elastase-induced pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency. PMID:24787644

  9. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice.

    PubMed

    Martins-Olivera, Bruno Tadeu; Almeida-Reis, Rafael; Theodoro-Júnior, Osmar Aparecido; Oliva, Leandro Vilela; Neto Dos Santos Nunes, Natalia; Olivo, Clarice Rosa; Vilela de Brito, Marlon; Prado, Carla Máximo; Leick, Edna Aparecida; Martins, Mílton de Arruda; Oliva, Maria Luiza Vilela; Righetti, Renato Fraga; Tibério, Iolanda de Fátima Lopes Calvo

    2016-01-01

    Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD). However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI) to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group) or saline (SAL group) and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups). At day 28, the following analyses were performed: (I) lung mechanics, (II) exhaled nitric oxide (ENO), (III) bronchoalveolar lavage fluid (BALF), and (IV) lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment. PMID:27528793

  10. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice

    PubMed Central

    Martins-Olivera, Bruno Tadeu; Theodoro-Júnior, Osmar Aparecido; Oliva, Leandro Vilela; Neto dos Santos Nunes, Natalia; Olivo, Clarice Rosa; Vilela de Brito, Marlon; Prado, Carla Máximo; Leick, Edna Aparecida; Martins, Mílton de Arruda

    2016-01-01

    Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD). However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI) to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group) or saline (SAL group) and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups). At day 28, the following analyses were performed: (I) lung mechanics, (II) exhaled nitric oxide (ENO), (III) bronchoalveolar lavage fluid (BALF), and (IV) lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment. PMID:27528793

  11. A rabbit ear model for cold stress testing.

    PubMed

    Smith, T L; Gordon, S; Holden, M B; Smith, B P; Russell, G B; Koman, L A

    1994-01-01

    A rabbit ear model resembling the human digit was studied to determine the vascular response of the rabbit ear to a cold stress. Following moderate cooling (10 minutes at 5 degrees - 8 degrees C), auricular blood flow and cutaneous perfusion were reduced. This decrease was reversed by 30 minutes of warming. The response in the rabbit ear to cold stress is similar to that of normal human digits. The similarities between the control of the circulation in human digits and rabbit ears may result from the similarities in digital and auricular vascular receptors and receptor subtypes. Verification of the rabbit model provides an experimental method for obtaining important data regarding digital pathophysiology and the treatment of cold intolerance. Further study with this model will provide clinically relevant information regarding the pathophysiology of digital thermoregulatory abnormalities. PMID:7830538

  12. Reversal of elastase-induced pulmonary emphysema and promotion of alveolar epithelial cell proliferation by simvastatin in mice.

    PubMed

    Takahashi, Saeko; Nakamura, Hidetoshi; Seki, Makoto; Shiraishi, Yoshiki; Yamamoto, Miyuki; Furuuchi, Momoyo; Nakajima, Takahiro; Tsujimura, Shuko; Shirahata, Toru; Nakamura, Miho; Minematsu, Naoto; Yamasaki, Motohiro; Tateno, Hiroki; Ishizaka, Akitoshi

    2008-05-01

    Besides lowering cholesterol, statins exert multiple effects, such as anti-inflammatory activity and improvement of endothelial cell function. We examined whether simvastatin (SS) protects against the development of elastase-induced pulmonary emphysema in mice by using mean linear intercepts of alveoli (Lm) as a morphometric parameter of emphysema. After injection of intratracheal elastase on day 0, C57BL/6 mice were treated daily with SS (SS+ group) or PBS (SS- group) for 2 wk. A 21% decrease in Lm on day 7 was observed in the SS+ group vs. the SS- group. Anti-inflammatory effects of SS were observed as a decrease in percentage of neutrophils up to day 3, and in hydroxyproline concentration on day 3, in bronchoalveolar lavage fluid (BALF). SS also increased the number of proliferating cell nuclear antigen (PCNA)-positive alveolar epithelial cells between days 3 and 14. To confirm the role of statins in promoting proliferation of alveolar cells, mice were treated with SS (SS+) vs. PBS (SS-) for 12 days, starting 3 wk after elastase administration. After SS treatment, Lm decreased by 52% and PCNA-positive alveolar epithelial cells increased compared with the SS- group. Concentrations of vascular endothelial growth factor in BALF and endothelial nitric oxide synthase protein expression in pulmonary vessels tended to be higher in the SS+ group vs. the SS- group in this protocol. In conclusion, SS inhibited the development of elastase-induced pulmonary emphysema in mice. This therapeutic effect was due not only to anti-inflammation but also to the promotion of alveolar epithelial cell regeneration, partly mediated by restoring endothelial cell functions. PMID:18310229

  13. Pancreas tumor model in rabbit imaged by perfusion CT scans

    NASA Astrophysics Data System (ADS)

    Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.

    2013-03-01

    The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.

  14. A rabbit model for study of Mycobacterium paratuberculosis infection.

    PubMed Central

    Mokresh, A H; Czuprynski, C J; Butler, D G

    1989-01-01

    Of 21 newborn rabbits inoculated orally with Mycobacterium paratuberculosis ATCC 19698, 13 (62%) became infected, as determined by histopathology and culture. Of the 21 inoculated rabbits, 14 (67%) experienced episodes of intermittent diarrhea, sometimes as early as 5 months after inoculation. Feces varied in consistency from soft-semisolid to watery. The organism was isolated from the sacculus rotundus, vermiform appendix of the cecum, ileum, mesenteric lymph node, and feces of 9 of 21 (43%) M. paratuberculosis-inoculated rabbits 8 to 10 months after inoculation. One infected rabbit gradually became severely emaciated; advanced paratuberculosis was confirmed by culture and histopathology. Of 21 rabbits, 9 (43%) developed multifocal, well-demarcated granulomatous enteritis in the sacculus rotundus and the vermiform appendix of the cecum. There was no significant difference in the rate of infection when the organisms were administered daily for 5 or 10 days in cow milk or broth. There was no discernible effect of pregnancy, parturition, or lactation on the severity of intestinal lesions, clinical signs, or the number of rabbits infected. Complement fixation and delayed-type hypersensitivity skin tests failed to detect infection. The results of this study suggest that newborn rabbits inoculated orally with M. paratuberculosis constitute a useful animal model for the study of paratuberculosis infection. Images PMID:2807547

  15. Simple adult rabbit model for Campylobacter jejuni enteritis.

    PubMed Central

    Caldwell, M B; Walker, R I; Stewart, S D; Rogers, J E

    1983-01-01

    We tested the usefulness of the Removable Intestinal Tie Adult Rabbit Diarrhea model to establish Campylobacter jejuni infection in rabbits. The procedure involved ligation of the cecum, placement of a slip knot at the terminal ileum, and injection of the test inoculum into the mid-small bowel. The ends of the slip knot were externalized, and the tie was released 4 h later. Fifty-five rabbits received C. jejuni, and 16 received uninoculated medium as controls. Daily rectal swabs were positive for 2 weeks in infected rabbits. The diarrheal attack rate was 64% in infected rabbits and 0% in controls. Diarrhea was characterized by loose, mucus-containing stools after an incubation period ranging from 24 h to 6 days. When blood was obtained daily for culture from 30 rabbits for 4 days post-challenge, bacteremia was present in 96.3% 24 h after challenge but diminished to 5 of 19 (26.3%) at 96 h. Death occurred in 53% of rabbits and was always preceded by diarrhea. No control animal died. Only 5 of 35 animals experiencing diarrhea recovered. An indirect whole-cell enzyme-linked immunosorbent assay was used to determine serum immunoglobulin G responses. Mean titers rose from 1:198 preoperatively to 1:9,087 on day 28. Necropsy on eight infected and two control animals showed inflammatory lesions with ulceration in 62.5% and goblet cell hyperplasia in 75% of infected rabbits. We conclude that the Removable Intestinal Tie Adult Rabbit Diarrhea procedure is a simple, effective method to establish C. jejuni infection which mimics human disease. Images PMID:6642664

  16. Bone marrow-derived endothelial progenitor cells are involved in aneurysm repair in rabbits.

    PubMed

    Fang, Xinggen; Zhao, Rui; Wang, Kuizhong; Li, Zifu; Yang, Penfei; Huang, Qinghai; Xu, Yi; Hong, Bo; Liu, Jianmin

    2012-09-01

    Endothelial progenitor cells (EPC) are believed to be involved in aneurysmal repair and remodeling. The aim of this study was to test this hypothesis and, if true, explore how EPC contribute to aneurysm repair in a rabbit model of elastase-induced carotid aneurysm. Rabbits were divided randomly into an in situ carotid EPC transfusion group (ISCT group, n=5), and an intravenous EPC transfusion group (IVT group, n=5). Autologous EPC were double-labeled with Hoechst 33342 and 5,6-carboxyfluorescein diacetate succinimidyl ester before injection into the animals in either the carotid artery (ISCT group) or marginal ear veins (IVT group). Three weeks later, labeled cells in the aneurysms were observed with respect to location, adhesion, and growth to detect signs of aneurysm repair. Labeled EPC were detected within the neointima in all five aneurysms in the ISCT group and in three of the five aneurysms in the IVT group, but there was no endothelial growth in the aneurysmal neointima in either group. These results show that bone marrow-derived EPC are involved in the process of aneurysm repair in this rabbit model. PMID:22789632

  17. Neurological Assessment Scores in Rabbit Embolic Stroke Models

    PubMed Central

    Brown, Aliza; Woods, Sean; Skinner, Robert; Hatton, Jeff; Lowery, John; Roberson, Paula; Hennings, Leah; Culp, William C

    2013-01-01

    Background: Neurological outcomes and behavioral assessments are widely used in animal models of stroke, but assessments in rabbit models are not fully validated. The wryneck model of neurological assessment scores (NAS) was compared to percent infarct volume (%IV) values (infarct volume is a proven clinical indicator of stroke severity) and arterial occlusion localization in three rabbit angiographic stroke models. Hypothesis: NAS values will correlate with percent infarct volume values. Methods: Anesthetized New Zealand White rabbits (N=131, 4-5 kg) received internal carotid artery emboli by angiographic catheter introduced into the femoral artery and occlusions were characterized. Rabbits were evaluated at 24 hours post embolism using the NAS test of 0 (normal) to 10 (death). Deficit criteria included neck twist, righting reflex, extension reflex in hind paw and forepaw, and posture. Brain sections stained with triphenyltetrazolium chloride (TTC) were analyzed for %IV. Volume of the infarct was measured and calculated as a percent of the total brain volume. Results: The aggregate correlation for NAS values vs. %IV values was R=0.61, p<0.0001, a strong positive relationship, while correlations of the NAS components ranged from R=0.28-0.46. Occlusionsof the posterior cerebral artery vs. the middle cerebral artery alone produced significantly greater deficit scores at p<0.0001. Conclusions: These positive results validate the NAS system in the rabbit angiographic embolic stroke model. PMID:24265650

  18. Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

    PubMed

    Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

    2015-01-01

    Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema. PMID:25757189

  19. The rabbit as an infection model for equine proliferative enteropathy

    PubMed Central

    Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

    2013-01-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  20. The rabbit as an infection model for equine proliferative enteropathy.

    PubMed

    Sampieri, Francesca; Allen, Andrew L; Pusterla, Nicola; Vannucci, Fabio A; Antonopoulos, Aphroditi J; Ball, Katherine R; Thompson, Julie; Dowling, Patricia M; Hamilton, Don L; Gebhart, Connie J

    2013-04-01

    The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

  1. Subject-Specific Computational Modeling of Evoked Rabbit Phonation.

    PubMed

    Chang, Siyuan; Novaleski, Carolyn K; Kojima, Tsuyoshi; Mizuta, Masanobu; Luo, Haoxiang; Rousseau, Bernard

    2016-01-01

    When developing high-fidelity computational model of vocal fold vibration for voice production of individuals, one would run into typical issues of unknown model parameters and model validation of individual-specific characteristics of phonation. In the current study, the evoked rabbit phonation is adopted to explore some of these issues. In particular, the mechanical properties of the rabbit's vocal fold tissue are unknown for individual subjects. In the model, we couple a 3D vocal fold model that is based on the magnetic resonance (MR) scan of the rabbit larynx and a simple one-dimensional (1D) model for the glottal airflow to perform fast simulations of the vocal fold dynamics. This hybrid three-dimensional (3D)/1D model is then used along with the experimental measurement of each individual subject for determination of the vocal fold properties. The vibration frequency and deformation amplitude from the final model are matched reasonably well for individual subjects. The modeling and validation approaches adopted here could be useful for future development of subject-specific computational models of vocal fold vibration. PMID:26592748

  2. A rabbit model of non-typhoidal Salmonella bacteremia

    PubMed Central

    Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M.; McLeod, Charles G.; Levine, Myron M.; Rothman, Richard E.; Gaydos, Charlotte A.; DeTolla, Louis J.

    2014-01-01

    Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. PMID:25033732

  3. Otoplasty Outcomes With Different Suture Materials in a Rabbit Model.

    PubMed

    Taylor, Benjamin A; Hong, Paul

    2016-03-01

    Otoplasty is a commonly performed procedure to correct prominent ears. Many different otoplasty techniques have been described but there is no gold standard technique. As well, many different suture materials are used in otoplasty but studies directly comparing different sutures materials are lacking. An otoplasty outcome study with Nylon and Mersilene (2 of the most commonly used sutures in otoplasty) sutures was conducted using a rabbit model. Each rabbit ear was randomized to receive a Mustardé-type horizontal mattress suture with either 4-0 clear Nylon (N = 12 ears) or 4-0 Mersilene sutures (N = 12 ears). Two weeks after surgery, the auricular bend angle was measured with a finger goniometer and histologic analysis with hematoxylin and eosin staining was performed on the rabbit auricular cartilage. Overall, there was no significant difference in the mean bend angle between the 2 groups (Nylon: 135.8°, SD = 22.7° and Mersilene: 143.2°, SD = 19.7°; P = 0.559). Also, no qualitative difference was observed on histologic analysis between the 2 suture groups. In the current rabbit model study, both Nylon and Mersilene sutures performed well and no significant differences were noted. PMID:26967081

  4. Computational rabbit models to investigate the initiation, perpetuation, and termination of ventricular arrhythmia.

    PubMed

    Arevalo, Hermenegild J; Boyle, Patrick M; Trayanova, Natalia A

    2016-07-01

    Current understanding of cardiac electrophysiology has been greatly aided by computational work performed using rabbit ventricular models. This article reviews the contributions of multiscale models of rabbit ventricles in understanding cardiac arrhythmia mechanisms. This review will provide an overview of multiscale modeling of the rabbit ventricles. It will then highlight works that provide insights into the role of the conduction system, complex geometric structures, and heterogeneous cellular electrophysiology in diseased and healthy rabbit hearts to the initiation and maintenance of ventricular arrhythmia. Finally, it will provide an overview on the contributions of rabbit ventricular modeling on understanding the mechanisms underlying shock-induced defibrillation. PMID:27334789

  5. Lung volumes and respiratory mechanics in elastase-induced emphysema in mice.

    PubMed

    Hantos, Z; Adamicza, A; Jánosi, T Z; Szabari, M V; Tolnai, J; Suki, B

    2008-12-01

    Absolute lung volumes such as functional residual capacity, residual volume (RV), and total lung capacity (TLC) are used to characterize emphysema in patients, whereas in animal models of emphysema, the mechanical parameters are invariably obtained as a function of transrespiratory pressure (Prs). The aim of the present study was to establish a link between the mechanical parameters including tissue elastance (H) and airway resistance (Raw), and thoracic gas volume (TGV) in addition to Prs in a mouse model of emphysema. Using low-frequency forced oscillations during slow deep inflation, we tracked H and Raw as functions of TGV and Prs in normal mice and mice treated with porcine pancreatic elastase. The presence of emphysema was confirmed by morphometric analysis of histological slices. The treatment resulted in an increase in TGV by 51 and 44% and a decrease in H by 57 and 27%, respectively, at 0 and 20 cmH(2)O of Prs. The Raw did not differ between the groups at any value of Prs, but it was significantly higher in the treated mice at comparable TGV values. In further groups of mice, tracheal sounds were recorded during inflations from RV to TLC. All lung volumes but RV were significantly elevated in the treated mice, whereas the numbers and size distributions of inspiratory crackles were not different, suggesting that the airways were not affected by the elastase treatment. These findings emphasize the importance of absolute lung volumes and indicate that tissue destruction was not associated with airway dysfunction in this mouse model of emphysema. PMID:18845778

  6. Periadventitial adipose-derived stem cell treatment halts elastase-induced abdominal aortic aneurysm progression

    PubMed Central

    Blose, Kory J; Ennis, Terri L; Arif, Batool; Weinbaum, Justin S; Curci, John A; Vorp, David A

    2014-01-01

    Aim Demonstrate that periadventitial delivery of adipose-derived mesenchymal stem cells (ADMSCs) slows aneurysm progression in an established murine elastase-perfusion model of abdominal aortic aneurysm (AAA). Materials & methods AAAs were induced in C57BL/6 mice using porcine elastase. During elastase perfusion, a delivery device consisting of a subcutaneous port, tubing and porous scaffold was implanted. Five days after elastase perfusion, 100,000 ADMSCs were delivered through the port to the aorta. After sacrifice at day 14, analyzed metrics included aortic diameter and structure of aortic elastin. Results ADMSC treated aneurysms had a smaller diameter and less fragmented elastin versus saline controls. Conclusion Periadventitial stem cell delivery prevented the expansion of an established aneurysm between days 5 and 14 after elastase perfusion. PMID:25431910

  7. Rabbit Models of Ocular Diseases: New Relevance for Classical Approaches.

    PubMed

    Zernii, Evgeni Y; Baksheeva, Viktoriia E; Iomdina, Elena N; Averina, Olga A; Permyakov, Sergei E; Philippov, Pavel P; Zamyatnin, Andrey A; Senin, Ivan I

    2016-01-01

    Over 100 million individuals are affected by irreversible visual impairments and blindness worldwide, while ocular diseases remain a challenging problem despite significant advances in modern ophthalmology. Development of novel drugs and drug delivery mechanisms, as well as advanced ophthalmological techniques requires experimental models including animals, capable of developing ocular diseases with similar etiology and pathology, suitable for future trials of new therapeutic approaches. Although experimental ophthalmology and visual research are traditionally performed on rodent models, these animals are often unsuitable for pre-clinical drug efficacy and safety studies, as well as for testing novel drug delivery approaches, e.g. controlled release of pharmaceuticals using intra-ocular implants. Therefore, rabbit models of ocular diseases are particularly useful in this context, since rabbits can be easily handled, while sharing more common anatomical and biochemical features with humans compared to rodents, including longer life span and larger eye size. This review provides a brief description of clinical, morphological and mechanistic aspects of the most common ocular diseases (dry eye syndrome, glaucoma, age-related macular degeneration, light-induced retinopathies, cataract and uveitis) and summarizes the diversity of current strategies for their experimental modeling in rabbits. Several applications of some of these models in ocular pharmacology and eye care strategies are also discussed. PMID:26553163

  8. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

    PubMed

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

    2015-02-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. PMID:25277507

  9. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    PubMed

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-02-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

  10. The characterization of a rabbit model of inflammatory bowel disease.

    PubMed Central

    Anthony, D.; Savage, F.; Sams, V.; Boulos, P.

    1995-01-01

    The absence of a simple, clinically relevant, animal model of inflammatory bowel disease (IBD) hampers research into this disease. In this study, colitis was induced in rabbits by intracolonic installation of 2,4,6-trinitrobenzene sulphonic acid (TNB) in 25% ethanol. Rabbits were killed from zero hours to 6 weeks and their colons examined. Rabbits were examined by endoscopy at weekly intervals. A single dose of TNB in ethanol produced dose dependent inflammation and ulceration, which at its optimum (40 mg) resulted in cobblestoning, strictures, and bowel wall thickening. The damage score at endoscopy was consistent with the score on macroscopic examination of the colon. Histopathological features of inflammation and ulceration observed in all animals that received 40 mg TNB included crypt abscesses, ulceration, crypt architectural distortion and, occasionally, granulomas and pseudopolyps. These changes, which are similar to those observed in IBD, persisted for 6 weeks. No lasting abnormalities were observed in control animals treated with TNB in saline, with ethanol alone, or with saline only. Histopathological similarity and the prolonged duration of inflammation, compared to other models, make this a suitable model for investigating inflammation in the colon. Furthermore, the model is accessible to endoscopy which adds to its value in experimental studies. Images Figure 1 Figure 2 PMID:7547433

  11. Rabbit Model for Superantigen-Mediated Lethal Pulmonary Disease.

    PubMed

    Strandberg, Kristi L; Rotschafer, Jessica H; Schlievert, Patrick M

    2016-01-01

    Staphylococcus aureus is a highly significant cause of serious human infections in the USA. Many of these illnesses are mediated by interactions between the host immune system and staphylococcal superantigens (SAgs). Several of these severe staphylococcal infections are initiated in the lungs, making this an important site to study. Here, we describe the rabbit model for investigating the role of staphylococcal SAgs in pulmonary-associated lethal infection and intoxication. PMID:26676039

  12. EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT

    NASA Astrophysics Data System (ADS)

    Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

    2015-07-01

    Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.

  13. EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT

    PubMed Central

    Xiaokaiti, Yilixiati; Wu, Haoming; Chen, Ya; Yang, Haopeng; Duan, Jianhui; Li, Xin; Pan, Yan; Tie, Lu; Zhang, Liangren; Li, Xuejun

    2015-01-01

    Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. PMID:26177797

  14. A novel rabbit model for studying RPE transplantation

    PubMed Central

    Cong, Lidan; Sun, Dawei; Zhang, Zhongyu; Jiao, Wanqiu; Rizzolo, Lawrence J.; Peng, Shaomin

    2008-01-01

    Purpose The goal of this project is to develop a model of retinal pigment epithelium (RPE) transplantation that permits extensive and reliable analysis of the transplants. Methods Cultures of newborn rabbit RPE were evaluated by morphology, electrophysiology and the expression of zonula occludens-1, cytokeratin and a melanocyte marker (S-100). Cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) were transplanted into the subretinal space of rabbits using a 30 gauge needle without making a conjunctival flap or sclerotomy. The transplants were examined by fundus photography, confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT) and angiography. At two months the retina was examined histochemically. Results A one minute incubation at 37°C with 20μM CFDA-SE did not affect morphology or the expression of marker proteins. In co-culture, the labeled cells integrated into monolayers that developed a normal transepithelial electrical resistance of 400-450 Ωcm2. Dye was not transferred from labeled to non-labeled RPE cells. Transplanted RPE was detectable for at least 2 months. Angiography demonstrated an intact blood retinal barrier. The normal morphology of the retina and lack of debris in the subretinal space, suggested the transplanted RPE was functional. Conclusions Primary cultures of newborn rabbit RPE were highly differentiated even when labeled with CFDA-SE. Labeled cells could be followed long-term in vitro and in vivo. This model can examine how culture and transplantation protocols affect the reformation of a functional RPE monolayer. The similar size of rabbit and human eyes will facilitate the translation of these protocols to the bedside. PMID:18502985

  15. Pathologic Findings in Rabbit Models of Hereditary Hypertriglyceridemia and Hereditary Postprandial Hypertriglyceridemia

    PubMed Central

    Mitsuguchi, Yoko; Ito, Tsunekata; Ohwada, Kazuo

    2008-01-01

    In recent years, the association between hyperlipidemia and the development of arteriosclerosis has been addressed in several studies. Rabbit models of hypertriglyceridemia (TGH) and postprandial hypertriglyceridemia (PHT) have been developed at the authors' institute. TGH rabbits manifest pathology similar to that of humans with TGH, such as xanthoma, in addition to atherosclerosis of arterioles. Furthermore, PHT rabbits show visceral obesity, insulin resistance, and impaired glucose tolerance, with pathologic features similar to those of the metabolic syndrome assumed to be the cause of human ischemic heart disease. This study was designed to investigate the histopathologic features of TGH and PHT rabbits. TGH rabbits showed advanced aortic atherosclerosis, accompanied by intimal thickening of coronary and renal arteries, fatty liver changes, and xanthoma. PHT rabbits demonstrated aortic intimal thickening and hepatic fatty degeneration. The results of this study suggest that TGH and PHT rabbits are useful animal models for studying human hyperlipidemia and metabolic syndrome and the cardiovascular diseases that result from these conditions. PMID:19004373

  16. Assessing anticalcification treatments in bioprosthetic tissue by using the New Zealand rabbit intramuscular model.

    PubMed

    Wright, Gregory A; Faught, Joelle M; Olin, Jane M

    2009-06-01

    The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague-Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm(-1) which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

  17. Radioisotopic model for investigating thromboembolism in the rabbit

    SciTech Connect

    May, G.R.; Herd, C.M.; Butler, K.D.; Page, C.P. )

    1990-08-01

    111Indium ({sup 111}In)-oxine labeled platelets have been used in a variety of species to assess platelet behavior in vivo. We have shown that {sup 111}In-oxine is a suitable label for rabbit platelets and, using a noninvasive technique for the automated, continuous, external imaging of these radiolabeled platelets, we have shown that intravenous adenosine disphosphate (ADP), collagen, platelet activating factor (PAF), and thrombin all elicit dose-related accumulation of platelet-(but not erythrocyte-)associated radioactivity in the thoracic region and a concomitant fall in both the cranial and hindlimb regions of the anesthetized rabbit. Intracarotid (i.c.) ADP, collagen, PAF, and thrombin also produce dose-related increases in platelet-associated radioactivity in the thoracic and decreases in the cranial and hindlimb regions. However, the initial fall in cranial counts induced by i.c. thrombin was followed by a marked increase that was sustained for up to 3 hr. These results suggest this may be a useful model for investigating the mechanisms of platelet activation in the arterial and venous circulations in vivo and may provide a novel model for investigating thromboembolic events in the cerebral circulation.

  18. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

    PubMed Central

    Kamaruzaman, Nurfatin Asyikhin; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

    2013-01-01

    No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy. PMID:23653896

  19. Percutaneous Ultrasound Guided Implantation of VX2 for Creation of a Rabbit Hepatic Tumor Model

    PubMed Central

    White, Sarah B.; Chen, Jeane; Gordon, Andrew C.; Harris, Kathleen R.; Nicolai, Jodi R.; West, Derek L.; Larson, Andrew C.

    2015-01-01

    Creation of a VX2 tumor model has traditionally required a laparotomy and surgical implantation of tumor fragments. Open surgical procedures are invasive and require long procedure times and recovery that can result in post-operative morbidity and mortality. The purpose of this study is to report the results of a percutaneous ultrasound guided method for creation of a VX2 model in rabbit livers. A total of 27 New Zealand white rabbits underwent a percutaneous ultrasound guided approach, where a VX2 tumor fragment was implanted in the liver. Magnetic resonance imaging was used to assess for tumor growth and necropsy was performed to determine rates of tract seeding and metastatic disease. Ultrasound guided tumor implantation was successful in all 27 rabbits. One rabbit died 2 days following the implantation procedure. Two rabbits had no tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26 (92%) rabbits. During the follow-up period, tract seeding was seen in 8% of rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous ultrasound guided tumor implantation safely provides reliable tumor growth for establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract seeding, compared to previously reported methods. PMID:25853660

  20. A novel total knee arthroplasty infection model in rabbits.

    PubMed

    Craig, Matthew R; Poelstra, Kornelis A; Sherrell, J Christopher; Kwon, Michael S; Belzile, Etienne L; Brown, Thomas E

    2005-09-01

    Infection of biomaterial implants is an expensive and devastating complication of orthopaedic surgery historically ranging from less than 1% in primary total knee arthroplasty (TKA) to 10% in revision TKA. An in vivo animal model was developed to test the efficacy of innovative therapies for the prevention of biomaterial centered infections caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). Twenty-two New Zealand White rabbits were used in this study. After proper anesthesia, a stainless-steel screw with a high molecular weight polyethylene (UHMWPE) washer was cemented in a defect created in the intra-articular, non-articulating portion of the lateral femoral condyle of each knee. After closure of the joint capsule, each knee was inoculated with 0, 10(2), 10(3), or 10(4) colony forming units (CFU) of MRSA. Animals were sacrificed after 7 days at which time joint aspirate, tissues and biomaterial samples were examined for evidence of infection. A total of 42 knees were used for analysis. When saline was injected into the knee, 0/10 of the knees demonstrated evidence of biomaterial centered infection (with the contralateral knee receiving 10(4)CFU MRSA). Four of 10 knees developed a biomaterial centered infection when 10(2)CFU MRSA was introduced. Seven out of 10 knees developed a biomaterial centered infection when either 10(3) or 10(4)CFU MRSA was injected. No evidence of septicemia (positive blood cultures) was found in any animal. This rabbit knee model utilizes commonly employed inexpensive orthopaedic implant materials in an in vivo milieu and provides an effective method for the evaluation of treatments for biomaterial centered infections. PMID:15927441

  1. The Asymmetric Vascular Stent: Efficacy in a rabbit aneurysm model

    PubMed Central

    Ionita, Ciprian N; Paciorek, Ann M; Dohatcu, Andreea; Hoffmann, Kenneth R; Bednarek, Daniel R; Kolega, John; Levy, Elad I; Hopkins, L. Nelson; Rudin, Stephen; Mocco, J.

    2009-01-01

    Background and Purpose Development of hemodynamic modifying devices to treat intracranial aneurysms (IAs) is an active area of research. The asymmetric vascular stent (AVS), a stent containing a low porosity patch, is such device. We evaluate AVS efficacy in an in vivo IA model. Methods We created twenty-four elastase rabbit model aneurysms: thirteen treated with the AVS, five treated with standard coronary stents, and six untreated controls. Four weeks following treatment, aneurysms underwent follow-up angiography, cone-beam micro-CT, histologic evaluation, and selective electron microscopy scanning. Results Four rabbits died early in the study: three during AVS treatment and one control (secondary to intra-procedural vessel injury and an unrelated tumor, respectively). AVS-treated aneurysms exhibited very weak or no aneurysm flow immediately after treatment and no flow in all aneurysms at follow-up. Stent-treated aneurysms showed flow both after treatment (5/5) and at follow-up (3/5). All control aneurysms remained patent during the study. Micro-CT scans showed: 9/9 of scanned AVS aneurysms were occluded, (6/9) AVSs were ideally placed and (3/9) the low porosity region partially covered the aneurysm neck; stent-treated aneurysms were 1/5 occluded, 2/5 patent, and 2/5 partially-patent. Histology results demonstrated: for AVS-treated aneurysms, advanced thrombus organization in the (9/9); for stent-treated aneurysms (1/4) no thrombus, (2/4) partially-thrombosed and (1/4) fully-thrombosed; for control aneurysms (4/4) no thrombus. Conclusion The use of AVSs shows promise as a viable new therapeutic in intracranial aneurysm treatment. These data encourage further investigation and provide substantial support to the AVS concept. PMID:19131663

  2. Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

    PubMed Central

    Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

    2015-01-01

    Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

  3. Modelling Landscape-Level Numerical Responses of Predators to Prey: The Case of Cats and Rabbits

    PubMed Central

    Cruz, Jennyffer; Glen, Alistair S.; Pech, Roger P.

    2013-01-01

    Predator-prey systems can extend over large geographical areas but empirical modelling of predator-prey dynamics has been largely limited to localised scales. This is due partly to difficulties in estimating predator and prey abundances over large areas. Collection of data at suitably large scales has been a major problem in previous studies of European rabbits (Oryctolagus cuniculus) and their predators. This applies in Western Europe, where conserving rabbits and predators such as Iberian lynx (Lynx pardinus) is important, and in other parts of the world where rabbits are an invasive species supporting populations of introduced, and sometimes native, predators. In pastoral regions of New Zealand, rabbits are the primary prey of feral cats (Felis catus) that threaten native fauna. We estimate the seasonal numerical response of cats to fluctuations in rabbit numbers in grassland–shrubland habitat across the Otago and Mackenzie regions of the South Island of New Zealand. We use spotlight counts over 1645 km of transects to estimate rabbit and cat abundances with a novel modelling approach that accounts simultaneously for environmental stochasticity, density dependence and varying detection probability. Our model suggests that cat abundance is related consistently to rabbit abundance in spring and summer, possibly through increased rabbit numbers improving the fecundity and juvenile survival of cats. Maintaining rabbits at low abundance should therefore suppress cat numbers, relieving predation pressure on native prey. Our approach provided estimates of the abundance of cats and rabbits over a large geographical area. This was made possible by repeated sampling within each season, which allows estimation of detection probabilities. A similar approach could be applied to predator-prey systems elsewhere, and could be adapted to any method of direct observation in which there is no double-counting of individuals. Reliable estimates of numerical responses are essential

  4. Transcatheter Arterial Embolization for Malignant Osseous and Soft-Tissue Sarcomas. I. A Rabbit Experimental Model

    SciTech Connect

    Nagata, Yasushi; Fujiwara, Kazuhisa; Okajima, Kaoru; Mitsumori, Michihide; Mizowaki, Takashi; Ohya, Natsuo; Hiraoka, Masahiro; Abe, Mitsuyuki; Ohura, Koitirou; Wataya, Shigeki

    1998-05-15

    Purpose: To evaluate the effect of transcatheter arterial embolization (TAE) on metastatic bone tumors in an experimental study. Methods: Fifteen Japanese white rabbits were transplanted with VX2 sarcoma cells into the iliac crest. In 10 rabbits, the arterial supply to the iliac bone tumors, internal iliac artery and iliolumbar artery were then embolized with particles of gelatin sponge. The therapeutic effect was evaluated by comparison with the natural course of control tumors in the other five rabbits. Results: After TAE, extensive necrosis, fibrosis, and vacuolization within the tumors were confirmed histologically. In the control rabbits, 19% {+-} 7% of the entire tumor was found to be spontaneous tumor necrosis; in contrast, the tumors of the TAE group showed necrosis as 62% {+-} 22% of the entire tumor. In one TAE group rabbit, no active tumor cell could be detected in the residual tumor. Conclusion: TAE was found to be an effective treatment for bone tumors in an experimental model.

  5. Jack Rabbit Pretest Shadowplate Drawings For TATB IHE Model Development

    SciTech Connect

    Hart, M M; McDaniel, D W

    2009-07-10

    The Jack Rabbit Pretest (PT) series consisted of 5 focused hydrodynamic experiments 2021E PT3, PT4, PT5, PT6, and PT7. They were fired in March and April of 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory, Livermore, California. These experiments measured deadzone formation and impulse gradients created during the detonation of TATB based insensitive high explosive. When setting up computer simulations of the Jack Rabbit Pretest series, the modeler or code developer can execute simulations with increasing degrees of refinement using detail found in the shadowplate design. The easiest way to get started is by treating the shadowplate in each experiment as a monolithic homogeneous piece of stainless steel. The simulation of detonation would begin as a point initiation below the center, bottom surface of the shadowplate. The detonation running through the ultrafine TATB booster can be simulated using program burn and then switched over to a reactive flow detonation model as the detonation front crosses the boundary into the main charge LX-17 IHE. A modeler wanting to further refine the simulation and progression of shock through the shadowplate can use the more detailed shadowplate design information presented in this document. The source drawings are included in Appendix A of this document. Their titles and drawing numbers are listed. Each experiment's shadowplate consists of two major components. A 303 stainless steel shape that defines the outer dimensions of shadowplate and a cylindrical 303 stainless steel detonator housing that is located in a closely machined pocket in the shape. The SIMPLE ASSY drawing accurately represents the dimensions of the outer shape, it's machined cylindrical pocket, and detonator body which is treated as a monolithic, homogeneous piece of stainless steel. The detonator body cross section shows an accurately dimensioned void where the slapper flyer barrel, LX-16 (pressed PETN) pellet, and pellet

  6. Sclareol exerts anti-osteoarthritic activities in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model

    PubMed Central

    Zhong, Ying; Huang, Yi; Santoso, Marcel B; Wu, Li-Dong

    2015-01-01

    Sclareol is a natural product initially isolated form Salvia sclarea which possesses immune-regulation and anti-inflammatory activities. However, the anti-osteoarthritic properties of sclareol have not been investigated. The present study is aimed at evaluating the potential effects of sclareol in interleukin-1β (IL-1β)-induced rabbit chondrocytes as well as an experimental rabbit knee osteoarthritis model induced by anterior cruciate ligament transection (ACLT). Cultured rabbit chondrocytes were pretreated with 1, 5 and 10 μg/mL sclareol for 1 h and followed by stimulation of IL-1β (10 ng/mL) for 24 h. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, tissue inhibitors of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MMP-3, TIMP-1, iNOS and COX-2 proteins were measured by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was applied for nitric oxide (NO) and prostaglandin E2 (PGE2) assessment. For the in vivo study, rabbits received six weekly 0.3 mL sclareol (10 μg/mL) intra-articular injections in the knees four weeks after ACLT surgery. Cartilage was harvested for measurement of MMP-1, MMP-3, MMP-13, TIMP-1, iNOS and COX-2 by qRT-PCR, while femoral condyles were used for histological evaluation. The in vitro results we obtained showed that sclareol inhibited the MMPs, iNOS and COX-2 expression on mRNA and protein levels, while increased the TIMP-1 expression. And over-production of NO and PGE2 was also suppressed. For the in vivo study, both qRT-PCR results and histological evaluation confirmed that sclareol ameliorated cartilage degradation. Hence, we speculated that sclareol may be an ideal approach for treating osteoarthritis. PMID:26045743

  7. Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

    PubMed

    Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

    2013-07-21

    There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. PMID:23567649

  8. Jack Rabbit Pretest Data For TATB Based IHE Model Development

    SciTech Connect

    Hart, M M; Strand, O T; Bosson, S T

    2008-06-18

    The Jack Rabbit Pretest series consisted of 5 focused hydrodynamic experiments, 2021E PT3, PT4, PT5, PT6, and PT7. They were fired in March and April of 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory, Livermore, California. These experiments measured dead-zone formation and impulse gradients created during the detonation of TATB based insensitive high explosive. This document contains reference data tables for all 5 experiments. These data tables include: (1) Measured laser velocimetry of the experiment diagnostic plate (2) Computed diagnostic plate profile contours through velocity integration (3) Computed center axis pressures through velocity differentiation. All times are in microseconds, referenced from detonator circuit current start. All dimensions are in millimeters. Schematic axi-symmetric cross sections are shown for each experiment. These schematics detail the materials used and dimensions of the experiment and component parts. This should allow anyone wanting to evaluate their TATB based insensitive high explosive detonation model against experiment. These data are particularly relevant in examining reactive flow detonation model prediction in computational simulation of dead-zone formation and resulting impulse gradients produced by detonating TATB based explosive.

  9. Gene Expression Profiles in a Rabbit Model of Systemic Lupus Erythematosus Autoantibody Production1

    PubMed Central

    Rai, Geeta; Ray, Satyajit; Milton, Jacqueline; Yang, Jun; Ren, Ping; Lempicki, Richard; Mage, Rose G.

    2010-01-01

    We previously reported the establishment of a rabbit (Oryctolagus cuniculus) model in which peptide immunization led to production of lupus-like autoantibodies including anti-Sm, -RNP, -SS-A, -SS-B and –dsDNA characteristic of those produced in Systemic Lupus Erythematosus (SLE) patients. Some neurological symptoms in form of seizures and nystagmus were observed. The animals used in the previous and in the present study were from a National Institute of Allergy and Infectious Diseases colony of rabbits that were pedigreed, immunoglobulin allotype-defined but not inbred. Their genetic heterogeneity may correspond to that found among patients of a given ethnicity. We extended the information about this rabbit model by microarray based expression profiling. We first demonstrated that human expression arrays could be used with rabbit RNA to yield information on molecular pathways. We then designed a study evaluating gene expression profiles in 8 groups of control and treated rabbits (47 rabbits in total). Genes significantly upregulated in treated rabbits were associated with NK cytotoxicity, antigen presentation, leukocyte migration, cytokine activity, protein kinases, RNA spliceosomal ribonucleoproteins, intracellular signaling cascades, and glutamate receptor activity. These results link increased immune activation with up-regulation of components associated with neurological and anti-RNP responses, demonstrating the utility of the rabbit model to uncover biological pathways related to SLE-induced clinical symptoms, including Neuropsychiatric Lupus. Our finding of distinct gene expression patterns in rabbits that made anti-dsDNA compared to those that only made other anti-nuclear antibodies should be further investigated in subsets of SLE patients with different autoantibody profiles. PMID:20817871

  10. Use of a potential rabbit model for structure--behavioral activity studies of cannabinoids.

    PubMed

    Consroe, P; Martin, A R; Fish, B S

    1982-05-01

    Using the genetically unique tetrahydrocannabinol-seizure susceptible (THC-SS) rabbit, the behavioral effect of 14 cannabinoids or related structures were determined and compared to the effects of 11 previously tested cannabinoids. Relative potencies of the cannabinoid-induced convulsions in THC-SS rabbits were generally comparable to reported relative potencies of cannabinoid-produced psychoactivity in humans and other behavioral activity in monkeys or other species. These data suggest that the THC-SS rabbit may represent an experimentally convenient and reliable animal model for studies of structure--psychoactivity relationships of marijuana-like compounds. PMID:7086846

  11. Experimental and finite element analysis of tibial stress fractures using a rabbit model

    PubMed Central

    Franklyn, Melanie; Field, Bruce

    2013-01-01

    AIM: To determine if rabbit models can be used to quantify the mechanical behaviour involved in tibial stress fracture (TSF) development. METHODS: Fresh rabbit tibiae were loaded under compression using a specifically-designed test apparatus. Weights were incrementally added up to a load of 30 kg and the mechanical behaviour of the tibia was analysed using tests for buckling, bone strain and hysteresis. Structural mechanics equations were subsequently employed to verify that the results were within the range of values predicted by theory. A finite element (FE) model was developed using cross-sectional computer tomography (CT) images scanned from one of the rabbit bones, and a static load of 6 kg (1.5 times the rabbit's body weight) was applied to represent running. The model was validated using the experimental strain gauge data, then geometric and elemental convergence tests were performed in order to find the minimum number of cross-sectional scans and elements respectively required for convergence. The analysis was then performed using both the model and the experimental results to investigate the mechanical behaviour of the rabbit tibia under compressive load and to examine crack initiation. RESULTS: The experimental tests showed that under a compressive load of up to 12 kg, the rabbit tibia demonstrates linear behaviour with little hysteresis. Up to 30 kg, the bone does not fail by elastic buckling; however, there are low levels of tensile stress which predominately occur at and adjacent to the anterior border of the tibial midshaft: this suggests that fatigue failure occurs in these regions, since bone under cyclic loading initially fails in tension. The FE model predictions were consistent with both mechanics theory and the strain gauge results. The model was highly sensitive to small changes in the position of the applied load due to the high slenderness ratio of the rabbit’s tibia. The modelling technique used in the current study could have applications

  12. Evaluating the Functionality of Conjunctiva Using a Rabbit Dry Eye Model

    PubMed Central

    Ning, Yuan; Bhattacharya, Dhruva; Jones, Richard E.; Zhao, Fangkun; Chen, Rongji; Zhang, Jinsong; Wang, Mingwu

    2016-01-01

    Purpose. To assess the conjunctival functionality in a rabbit dry eye (DE) model. Methods. Nictitating membrane, lacrimal and Harderian glands were surgically excised from male New Zealand white rabbits using minimally invasive surgery. Fluorescein/rose Bengal staining of ocular surface (OS) and Schirmer test were done before (BE) and after excision (AE). The expression of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, and MUC5AC proteins were estimated by immunoblotting from conjunctival impression cytology specimens. MUC5AC mRNA was quantified as well. The effect of epithelial sodium channel (ENaC) blockers on tear production and potential differences (PD) of OS were assessed under anesthesia in rabbits with and without surgery. Results. Increase in corneal and conjunctival staining was observed 1 month AE compared to BE. Schirmer tests failed to show decrease in tear production. Elevated IL-1β, and TNF-α, 1 month AE indicated inflammation. MUC5AC expression was elevated 1 month AE. ENaC blockers did not improve tear production in rabbit eyes AE but characteristic changes in PD were observed in rabbits with surgery. Conclusions. DE biomarkers are important tools for OS assessment and MUC5AC expression is elevated in rabbit DE. PD measurement revealed significant electrophysiological changes in rabbits with surgery. PMID:27088007

  13. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models.

    PubMed

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  14. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models

    PubMed Central

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y. Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  15. Urinary obstruction reduces glomerulogenesis in the developing kidney: a model in the rabbit.

    PubMed

    McVary, K T; Maizels, M

    1989-08-01

    To study the effect of unilateral ureteral obstruction upon the development of the kidney a fetal rabbit model was developed. A total of 27 rabbits underwent ureteral ligation in utero (24 days after conception) and 34 underwent ureteral ligation at term (30 days after conception). Two rabbits undergoing in utero ureteral ligation underwent decompression at term. Fetal development was evaluated by glomerular counts of mid sagittal sections of the kidney and compared to that of 67 normal rabbits, 43 littermates of rabbits undergoing surgery, 12 rabbits with missed ligation of the ureter and 4 whose ureters were ligated after the period of nephrogenesis had ended (57 days after conception). In the normal rabbit term occurred at 31 days after conception but nephrogenesis continued until 48 days when the cortical glomerular count reached approximately 650. Ligation of the ureter at 24 days led to a rapid decrease in cortical glomerular counts in the obstructed kidney but glomeruli developing within the nephrogenic cap were more resistant to the effects of the obstruction. Glomerular counts in the nonobstructed kidney were similar to those of littermates. Ligation of the ureter at 30 days produced similar findings. All operated fetuses and their littermates showed glomerular counts less than that of normal animals of the same age. In the 2 fetuses who underwent ureteral ligation at 24 days after conception and decompression at 30 days after conception sacrifice at 42 days after conception revealed that glomerular counts that had been reduced by 95 per cent by the obstruction showed 80 per cent recovery after decompression. It appears that renal development can be quantified by glomerular counts in the rabbit. Obstruction during fetal development reduces these counts while in a limited sample decompression of the obstructed kidney partially restores them. This model appears to be suitable for the study of the effects of fetal surgery upon renal function. PMID:2746793

  16. Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models

    PubMed Central

    Kowalski, Regis P.; Romanowski, Eric G.; Mah, Francis S.; Shanks, Robert M. Q.; Gordon, Y. J.

    2016-01-01

    Purpose To determine whether topical levofloxacin 1.5% will successfully treat both levofloxacin-resistant and susceptible Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) in rabbit keratitis models. Methods For levofloxacin-resistant and susceptible SA, respectively, 32 New Zealand White (NZW) rabbits were intrastromally injected with 1000 colony-forming units (CFU). After 4 hr, the corneas of eight rabbits were homogenized to determine onset CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, vancomycin (cefazolin for levofloxacin-susceptible SA) and saline. Twenty-one drops were administered over 5 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. For levofloxacin-resistant and susceptible PA, respectively, 32 NZW rabbits were intrastromally injected with 1000 CFU. After 16 hr, the corneas of eight rabbits were homogenized for CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, tobramycin (ciprofloxacin for levofloxacin-susceptible PA) and saline. Nineteen drops were administered over 8 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. The CFU/ml data were analysed for sterilization and non-parametrically for reduction. Results Levofloxacin 1.5% significantly reduced more (p < 0.05) levofloxacin-resistant SA than vancomycin; was equivalent to cefazolin (p > 0.05) for levofloxacin-susceptible SA; was equivalent to tobramycin for levofloxacin-resistant PA; was equivalent to ciprofloxacin for levofloxacin-susceptible PA; and significantly reduced more SA and PA than saline and onset. Levofloxacin 1.5% sterilized the corneas in the levofloxacin-resistant and susceptible PA groups (32/32) and levofloxacin-susceptible SA group (16/16), but not the levofloxacin-resistant SA group (0/16). Conclusion Levofloxacin 1.5% was effective for reducing SA and PA in the rabbit keratitis models regardless of in vitro resistance. PMID:20456251

  17. Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats

    SciTech Connect

    Damon, E.G.; Mokler, B.V.; Jones, R.K.

    1983-01-01

    The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, /sup 59/FE-labeled Fe/sub 2/O/sub 3/. Untreated rats or rats pretreated by intratracheal in stillation with elastase were exposed to an aerosol of /sup 59/Fe-labeled Fe/sub 2/O/sub 3/ either 18 hr or 7 days after exposure to aerosslized Triton X-100 which was administered in doses of 20, 100, or 200 ..mu..g/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of /sup 59/Fe than the untreated controls (p < 0.005). Pulmonary deposition of Fe/sub 2/O/sub 3/ was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe/sub 2/O/sub 3/. Triton X-100 administered 18 hr prior to exposure of rats to Fe/sub 2/O/sub 3/ aerosol resulted in dose-related increases in whole-body retention of /sup 59/Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe/sub 2/O/sub 3/, increased retention of /sup 59/Fe was noted only in those treated at the highest Triton X-100 dose level (200 ..mu..g/g). 20 references, 5 tables.

  18. Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model.

    PubMed

    Hu, Jiafen; Cladel, Nancy; Peng, Xuwen; Balogh, Karla; Christensen, Neil D

    2008-02-01

    Cottontail rabbit papillomavirus (CRPV)/rabbit model is widely used to study pathogenesis of papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software. PMID:18187239

  19. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

    PubMed

    Abela, Oliver G; Ahsan, Chowdhury H; Alreefi, Fadi; Salehi, Negar; Baig, Imran; Janoudi, Abed; Abela, George S

    2016-06-01

    Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis-often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy. PMID:27091328

  20. Feasibility and acute healing of vocal fold microflap incisions in a rabbit model

    PubMed Central

    Suehiro, Atsushi; Bock, Jonathan M.; Hall, Joseph E.; Garrett, C. Gaelyn; Rousseau, Bernard

    2012-01-01

    Objectives The purpose of this study was to: 1) investigate the feasibility of performing mucosal elevation of a vocal fold microflap in a rabbit model, and 2) measure the acute healing of rabbit microflap incisions compared to control vocal folds. Study Design Prospective animal study Methods Ten New Zealand white rabbits were used in this study. All rabbits received a 3mm incision through the epithelium of one vocal fold using a sickle knife and mucosal elevation through this incision using a microlaryngeal fine angled spatula. The contralateral vocal fold was left intact to serve as an internal control. Student t tests were used to investigate differences in epithelial thickness, immunohistochemical staining of CD 45, and inflammatory and pro-fibrotic gene expression between vocal folds undergoing microflap and control. Results Exposure of the rabbit larynx was achieved, allowing for the identification of a surgical plane and the creation of a microflap and elevation of the vocal fold mucosa. Hematoxylin-eosin staining revealed no significant differences in epithelial thickness, immunohistochemistry for CD 45 showed no significant differences in CD 45 positive cells, and quantitative PCR revealed no significant differences in IL-1β, TGFβ-1, or COX-2 gene expression between vocal folds undergoing microflap and control. Conclusions We demonstrate the feasibility of vocal fold microflap surgery in a rabbit model. With the advantage of greater access to primers and antibodies for molecular biological studies, the application of the microflap technique in a small animal model such as rabbit has broad implications for future experimental investigations in laryngology. Level of Evidence Animal Research. PMID:22253007

  1. Aggregation and Binding Substances Enhance Pathogenicity in Rabbit Models of Enterococcus faecalis Endocarditis

    PubMed Central

    Schlievert, Patrick M.; Gahr, Pamala J.; Assimacopoulos, Aris P.; Dinges, Martin M.; Stoehr, Jennifer A.; Harmala, John W.; Hirt, Helmut; Dunny, Gary M.

    1998-01-01

    We investigated the importance of enterococcal aggregation substance (AS) and enterococcal binding substance (EBS) in rabbit models of Enterococcus faecalis cardiac infections. First, American Dutch belted rabbits were injected intraventricularly with 108 CFU and observed for 2 days. No clinical signs of illness developed in animals given AS− EBS− organisms, and all survived. All rabbits given AS− EBS+ organisms developed signs of illness, including significant pericardial inflammation, but only one of six died. All animals given AS+ EBS− organisms developed signs of illness, including pericardial inflammation, and survived. All rabbits given AS+ EBS+ organisms developed signs of illness and died. None of the rabbits receiving AS+ EBS+ organisms showed gross pericardial inflammation. The lethality and lack of inflammation are consistent with the presence of a superantigen. Rabbit and human lymphocytes were highly stimulated in vitro by cell extracts, but not cell-free culture fluids, of AS+ EBS+ organisms. In contrast, cell extracts from AS− EBS− organisms weakly stimulated lymphocyte proliferation. Culture fluids from human lymphocytes stimulated with AS+/EBS+ enterococci contained high levels of gamma interferon and tumor necrosis factor alpha (TNF-α) and TNF-β, which is consistent with functional stimulation of T-lymphocyte proliferation and macrophage activation. Subsequent experiments examined the abilities of the same strains to cause endocarditis in a catheterization model. New Zealand White rabbits underwent transaortic catheterization for 2 h, at which time catheters were removed and animals were injected with 2 × 109 CFU of test organisms. None of the animals given AS− EBS− organisms developed vegetations or showed autopsy evidence of tissue damage. Rabbits given AS− EBS+ or AS+ EBS− organisms developed small vegetations and had splenomegaly at autopsy. All rabbits given AS+ EBS+ organisms developed large vegetations and had

  2. Terahertz spectroscopic imaging of a rabbit VX2 hepatoma model

    NASA Astrophysics Data System (ADS)

    Park, Jae Yeon; Choi, Hyuck Jae; Cho, Kyoung-Sik; Kim, Kyu-Rae; Son, Joo-Hiuk

    2011-03-01

    Terahertz (THz) spectroscopic imaging technique was applied to classify the tumor region in the rabbit liver with VX2 hepatocellular carcinoma. Within the measurement range of 0.1-2 THz, the average reflectance values for all tumor samples were more than 4% higher than those for healthy cells, and the terahertz measurements correlated well with histological analysis results. This study on paraffin-embedded tissues showed the alteration of cell density and protein content in tumors, excluding the effect of water.

  3. Controlled Release and Antitumor Effect of Pluronic F127 Mixed with Cisplatin in a Rabbit Model

    SciTech Connect

    Sonoda, Akinaga Nitta, Norihisa; Ohta, Shinich; Nitta-Seko, Ayumi; Morikawa, Shigehiro; Tabata, Yasuhiko; Takahashi, Masashi; Murata, Kiyoshi

    2010-02-15

    The purpose of this study was to evaluate pluronic F127 for the controlled release of cisplatin in a rabbit model. Pluronic F127 becomes liquid at temperatures <25{sup o}C and converts to a gelatinous state at temperatures between 25 and 60{sup o}C. Six Japanese white rabbits were injected with pluronic + cisplatin (n = 3, renal group A) or saline + cisplatin (n = 3, renal group B) to measure the platinum concentration in kidneys. Another 25 rabbits with VX2 liver tumors were divided into five equal groups. They were injected with saline, saline + cisplatin, iodized oil + cisplatin, pluronic alone, or pluronic + cisplatin and labeled as liver groups A, B, C, D, and E, respectively. The antitumor effect of pluronic was then assessed. In the presence of pluronic, the platinum concentration in the kidneys of rabbits remained relatively high. In animals with liver tumors, the delivery of pluronic + cisplatin produced higher tumor reduction rates (P < 0.05) than in the other groups, without apparent damage to normal liver tissue. We conclude that pluronic is useful for the controlled release of cisplatin in a rabbit model.

  4. A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. II. Intracranial contents, intracranial volume, and intracranial pressure.

    PubMed

    Mooney, M P; Siegel, M I; Burrows, A M; Smith, T D; Losken, H W; Dechant, J; Cooper, G; Fellows-Mayle, W; Kapucu, M R; Kapucu, L O

    1998-06-01

    This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis, and this second part presents neuropathological findings and age-related changes in intracranial volume (ICV) and intracranial pressure (ICP) in 106 normal rabbits and 56 craniosynostotic rabbits from this colony. Brain morphology and anteroposterior length were described in 44 rabbit fetuses and perinates (27 normal; 17 synostosed). Middle meningeal artery patterns were qualitatively assessed from 2-D PCC MRI VENC scans and endocranial tracings from 15, 126-day-old rabbits (8 normal, 7 rabbits with unicoronal synostosis). Brain metabolism was evaluated by assessing 18F-FDG uptake with high-resolution PET scanning in 7, 25-day-old rabbits (3 normal, 4 with unicoronal or bicoronal synostosis). Intracranial contents and ICV were assessed using 3-D CT scanning of the skulls of 30 rabbits (20 normal,10 with unicoronal synostosis) at 42 and 126 days of age. Serial ICP data were collected from 66 rabbits (49 normal; 17 with unicoronal synostosis) at 25 and 42 days of age. ICP was assessed in the epidural space using a Codman NeuroMonitor microsensor transducer. Results revealed that cerebral cortex morphology was similar between normal and synostosed fetuses around the time of synostosis. Significantly (P<0.05) decreased A-P cerebral hemisphere growth rates and asymmetrical cortical remodeling were noted with increasing age in synostotic rabbits. In addition, rabbits with unicoronal suture synostosis exhibited asymmetrical middle meningeal artery patterns, decreased and asymmetrical brain metabolism, a "beaten-copper" intracranial appearance, significantly (P<0.05) decreased ICV, and significantly (P<0.01) elevated ICP compared with normal control rabbits. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light

  5. Insights into Campylobacter jejuni colonization and enteritis using a novel infant rabbit model.

    PubMed

    Shang, Yuwei; Ren, Fangzhe; Song, Zhaojun; Li, Qiuchun; Zhou, Xiaohui; Wang, Xiaobo; Xu, Zhonglan; Bao, Guangyu; Wan, Ting; Lei, Tianyao; Wang, Nan; Jiao, Xin-An; Huang, Jinlin

    2016-01-01

    A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. Here we used an infant rabbit to study C. jejuni infection, which enables us to define several previously unknown but key features of the organism. C. jejuni is capable of systemic invasion in the rabbit, and developed a diarrhea symptom that mimicked that observed in many human campylobacteriosis. The large intestine was the most consistently colonized site and produced intestinal inflammation, where specific cytokines were induced. Genes preferentially expressed during C. jejuni infection were screened, and acs, cj1385, cj0259 seem to be responsible for C. jejuni invasion. Our results demonstrates that the infant rabbit can be used as an alternative experimental model for the study of diarrheagenic Campylobacter species and will be useful in exploring the pathogenesis of other related pathogens. PMID:27357336

  6. Insights into Campylobacter jejuni colonization and enteritis using a novel infant rabbit model

    PubMed Central

    Shang, Yuwei; Ren, Fangzhe; Song, Zhaojun; Li, Qiuchun; Zhou, Xiaohui; Wang, Xiaobo; Xu, Zhonglan; Bao, Guangyu; Wan, Ting; Lei, Tianyao; Wang, Nan; Jiao, Xin-an; Huang, Jinlin

    2016-01-01

    A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. Here we used an infant rabbit to study C. jejuni infection, which enables us to define several previously unknown but key features of the organism. C. jejuni is capable of systemic invasion in the rabbit, and developed a diarrhea symptom that mimicked that observed in many human campylobacteriosis. The large intestine was the most consistently colonized site and produced intestinal inflammation, where specific cytokines were induced. Genes preferentially expressed during C. jejuni infection were screened, and acs, cj1385, cj0259 seem to be responsible for C. jejuni invasion. Our results demonstrates that the infant rabbit can be used as an alternative experimental model for the study of diarrheagenic Campylobacter species and will be useful in exploring the pathogenesis of other related pathogens. PMID:27357336

  7. Establishment of a chronic left ventricular aneurysm model in rabbit

    PubMed Central

    Xiao, Cang-Song; Gao, Chang-Qing; Li, Li-Bing; Wang, Yao; Zhao, Tao; Ye, Wei-Hua; Ren, Chong-Lei; Liu, Zhi-Yong; Wu, Yang

    2014-01-01

    Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm (LVA) in rabbits. Methods Acute myocardial infarction (AMI) was induced in 35 rabbits via concomitant ligation of the left anterior descending (LAD) coronary artery and the circumflex (Cx) branch at the middle portion. Development of AMI was confirmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar intra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure (LVESP) and diastolic pressure (LVEDP) were measured before, immediately after and four weeks after ligation. Dimensions of the ventricular chamber, thickness of the interventricular septum (IVS) and the left ventricular posterior wall (LVPW) left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), and ejection fraction (EF) were recorded by echocardiogram. Results Thirty one (88.6%) rabbits survived myocardial infarction and 26 of them developed aneurysm (83.9%). The mean area of aneurysm was 33.4% ± 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the LV that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce development of LVA at a mean area ratio of 33.4% ± 2.4% which involves the apex, anterior wall and lateral wall of the left ventricle. PMID:25009567

  8. Effects and mechanism of Xin Mai Jia in a rabbit model of atherosclerosis

    PubMed Central

    ZHAO, FAN-RONG; LU, JUN-XIU; JIA, MEI; YIN, YA-LING; QI, HENG-TIAN; ZHU, MO-LI; MA, LI-JUAN; QIU, LE-LE; WAN, GUANG-MING; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to investigate the protective effects of Xin Mai Jia (XMJ) on atherosclerosis (AS) in rabbits and to explore the underlying mechanisms in order to provide experimental evidence for the clinical application of XMJ. An intraperitoneal injection of vitamin D3, combined with a high-fat diet and sacculus injury, was utilized to establish the AS rabbit model. Following the oral administration of lovastatin, Zhibituo and different dosages of XMJ, respectively, blood was drawn from each rabbit for the detection of blood rheological indicators, such as serum lipids. The pathological changes in the right common carotid artery were observed. Vascular function experiments and the expression detection of common carotid artery-related proteins by immunohistochemistry were conducted. XMJ was observed to decrease the blood lipid levels of the AS rabbits; increase the concentration of high-density lipoprotein and apolipoprotein A; decrease blood viscosity, erythrocyte sedimentation rate and hematocrit; elevate the levels of endothelial nitric oxide synthase (eNOS) and Na+/H+ exchanger 1 in vascular tissues and decrease the levels of angiotensin II receptor, type 1 (AT-1) and endothelin-1 (ET-1). In conclusion, XMJ was shown to lower the blood lipid levels of the experimental AS rabbits, improve the abnormal changes in hemorheology, increase the eNOS content in the vascular tissue, decrease the AT-1 and ET-1 levels and increase the endothelium-dependent vasodilation reaction. XMJ therefore has an anti-AS effect. PMID:26640529

  9. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    NASA Astrophysics Data System (ADS)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  10. A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

    PubMed

    Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

    2016-06-30

    Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions. PMID:26924647

  11. Perforator pedicled sural neurocutaneous vascular flap: a modeling study in the rabbit

    PubMed Central

    Wen, Gen; Zhong, Wanrun; Lu, Shengdi; Wang, Chunyang; Han, Pei; Chai, Yimin

    2015-01-01

    Background: An animal model of a distal pedicled sural neurocutaneous flap for experimental research has not previously been established. The purpose of this study was to construct a sural neurocutaneous vascular flap model in the rabbit. Materials and methods: Thirty-five New England rabbits were divided into four groups. Five rabbits in Group A were used for an anatomical study. Red latex and gelatin-lead oxide were injected into posterior tibial arteries of five rabbits in Groups B and C, respectively. In Group D, 40 neurocutaneous flaps with a single perforator pedicle were raised bilaterally in twenty rabbits. In the right legs, 20 flaps were raised by the normal procedure. In the left legs, the perforator pedicles of 20 flaps were ligated as controls. Results: The sural nerve originated from the posterior tibial nerve. Its accompanying artery originated from the deep femoral artery and ran to the lateral malleolus following the sural nerve. A perforator of the posterior tibial artery at the superior calcaneus originated from the midpoint of the connecting line between the medial malleolus and calcaneus, and was 0.46 ± 0.03 mm in diameter at its origin. The survival rate of the flaps in the right leg 10 days after operation was 64.7 ± 8.7%. Flaps on the left side underwent total necrosis. Conclusion: The distal single perforator-based sural neurocutaneous vascular flap in the rabbit presents with anatomical stability, is easy to harvest, and has a reliable arterial supply. The developed method represents a useful animal model for the study of single perforator-based neurocutaneous vascular flaps. PMID:26131105

  12. Chronic achilles paratenonitis with tendinosis: an experimental model in the rabbit.

    PubMed

    Backman, C; Boquist, L; Fridén, J; Lorentzon, R; Toolanen, G

    1990-07-01

    An experimental model for inducing chronic Achilles paratenonitis with tendinosis in the rabbit is presented. Thirteen rabbits were exercised in a kicking machine producing passive flexions and extensions of the ankle joint. Active contractions of the triceps surae muscles were induced by electric stimulation via surface electrodes. The animals were exercised for 5 to 6 weeks, with a rate of 150 flexions and extensions per minute for 2 h, three times a week. Light microscopic examination showed degenerative changes of the tendon, and increased number of capillaries, infiltrates of inflammatory cells, edema, and fibrosis in the paratenon. We conclude that chronic Achilles paratenonitis with tendinosis can be experimentally induced in a standardized manner in rabbits. PMID:2355294

  13. The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases.

    PubMed

    Bősze, Z; Major, P; Baczkó, I; Odening, K E; Bodrogi, L; Hiripi, L; Varró, A

    2016-07-01

    Since the creation of the first transgenic rabbit thirty years ago, pronuclear microinjection remained the single applied method and resulted in numerous important rabbit models of human diseases, including cardiac deficiencies, albeit with low efficiency. For additive transgenesis a novel transposon mediated method, e.g., the Sleeping Beauty transgenesis, increased the efficiency, and its application to create cardiac disease models is expected in the near future. The targeted genome engineering nuclease family, e.g., the zink finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the newest, clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR associated effector protein (CAS), revolutionized the non-mouse transgenesis. The latest gene-targeting technology, the CRISPR/CAS system, was proven to be efficient in rabbit to create multi-gene knockout models. In the future, the number of tailor-made rabbit models produced with one of the above mentioned methods is expected to exponentially increase and to provide adequate models of heart diseases. PMID:27210304

  14. Establishment of Rabbit Abdominal Aortic Atherosclerosis Model by Pancreatic Elastase Infiltration Associated with High Fat Diet

    PubMed Central

    Liang, Song-Nian; Xu, Ke; Zhong, Hong-Shan

    2015-01-01

    Background The aim of this study was to evaluate the feasibility of a high fat diet (HFD) associated with pancreatic elastase (PE) infiltration, in establishing the rabbit aortic atherosclerosis model. Methods The HFD+PE method and the HFD+saccule injury (SI) method were simultaneously used to prepare the rabbit atherosclerosis model; the control group was established with the normal diet. Biochemical indicators, radiological imaging, pathomorphology and immunohistochemistry were used to evaluate the HFD+PE modeling results. Results There were significant changes in the blood lipid contents, as well as the pathomorphological and immunohistochemical results between the two experimental groups and the control group (p < 0.05). However, there was no difference between the two experimental groups. The rabbit aortic atherosclerosis model prepared by the HFD+PE method had no significant difference in the local vascular pathomorphological and immunohistochemical results with the traditional HFD+SI method. Conclusions The use of HFD with PE infiltration is feasible in establishing the rabbit aortic atherosclerosis model. PMID:27122900

  15. Construction of Radial Defect Models in Rabbits to Determine the Critical Size Defects

    PubMed Central

    Zhang, Xin-Chao; Gui, Ke-Ke; Xiong, Min; Yin, Wang-Ping; Yuan, Feng-Lai; Cai, Guo-Ping

    2016-01-01

    Many studies aimed at investigating bone repair have been conducted through animal models in recent years. However, limitations do exist in these models due to varying regeneration potential among different animal species. Even using the same animal, big differences exist in the size of critical size defects (CSD) involving the same region. This study aimed to investigate the standardization of radial bone defect models in rabbits and further establish more reliable CSD data. A total of 40 6-month-old New Zealand white rabbits of clean grade totaling 80 radial bones were prepared for bone defect models, according to the principle of randomization. Five different sizes (1.0, 1.2, 1.4, 1.7 and 2.0 cm) of complete periosteal defects were introduced under anesthesia. At 12 weeks postoperatively, with the gradual increase in defect size, the grades of bone growth were significantly decreased in all 5 groups. X-ray, CT scans and H&E staining of the 1.4, 1.7, and 2.0-cm groups showed lower grades of bone growth than that of the 1.0 and 1.2-cm groups respectively (P < 0.05). Using rabbit radial defect model involving 6-month-old healthy New Zealand white rabbits, this study indicates that in order to be critical sized, defects must be greater than 1.4 cm. PMID:26731011

  16. A new minimally invasive experimental spinal cord injury model in rabbits.

    PubMed

    Baydin, A; Cokluk, C; Aydin, K

    2007-06-01

    The aim of this experimental study was to evaluate the effectivity of epidural microballoon inflation into the unroofed spinal column for the creation of a new experimental spinal cord injury model in rabbits. 10 New Zealand white rabbits were used for this study. Before operation and after anasthesia with 50 mg/kg ketamine and 8 mg/kg xylazine, spinal evoked potentials (SEP) were recorded in all rabbits. A midline skin incision was done on the lomber skin at the level of L1-L4. Paravertebral muscles were dissected bilaterally. A microhemilaminotomy was done in the right L3 lamina close to the midline by using Midas-rex micro-diamond drill instruments. The ligamentum flavum was opened and removed with microscissors. A microballoon was inserted into the spinal column between the bone and dura mater to the level of T12. The microballoon was inflated by using a pressure- and volume-controlled microballoon inflation device. Pre-injury and post-injury SEPs were recorded. The microballoon was deflated 15 minutes later and removed completely from the epidural space. 24 hours later the SEP study was repeated. Following microballoon inflation the SEP waves dropped to the basal level. All rabbits were paraplegic after the operation. In conclusion, this experimental study demonstrated that the microballoon inflation technique is a very successful method for the evaluation of spinal cord injury in rabbits. Unroofing of the spinal column is extremely important because decompression may be an effective treatment in spinal cord injury. Also the traumatic effect of aneurysm clips represents a different type of injury to the spinal cord. This new model may be used in experimental studies of spinal cord injury in rabbits. PMID:17882754

  17. Renal Denervation Suppresses the Inducibility of Atrial Fibrillation in a Rabbit Model for Atrial Fibrosis.

    PubMed

    Wei, Yong; Xu, Juan; Zhou, Genqing; Chen, Songwen; Ouyang, Ping; Liu, Shaowen

    2016-01-01

    Renal denervation (RD) was reported to reduce the susceptibility of atrial fibrillation (AF), but the underlying mechanism has not been well understood. This study was performed to investigate the effect of RD on the inducibility of AF in a rabbit model for atrial fibrosis and to explore the potential mechanisms. Thirty-five rabbits were randomly assigned into sham-operated group (n = 12), abdominal aortic constriction (AAC) group (n = 12) and AAC with RD (AAC-RD) group (n = 11). The incidence of AF induced by burst pacing in atriums was determined. Blood was collected to measure the levels of rennin, angiotensin II and aldosterone. Atrial samples were preserved to evaluate protein and gene expression of collagen, connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1). Our data suggested cardiac structure remodeling and atrial fibrosis were successfully induced by AAC. Compared with the AAC group, the AAC-RD rabbits had smaller ascending aortic diameter and left ventricular end-systolic diameter. For burst pacing at the left atrium (LA), AF was induced in two of the 12 rabbits in the sham-operated group, 10 of the 12 rabbits in the AAC group, and 2 of the 11 rabbits in the AAC-RD group, with great difference among the three groups (P = 0.001). The percentage of LA burst stimulations with induced AF achieved 47.2% in the AAC group, which was higher than those in both the AAC-RD (12.1%) and the Sham-operated (5.6%) groups. Significantly increasing intercellular space in the AAC group (P<0.001) compared with the sham-operated rabbits. RD clearly decreased the volume fraction of collagen in LA and right atrium compared with that of the AAC group (P< 0.01). AAC-induced elevation of collagen I, CTGF and TGF-β1 was suppressed by RD. In conclusion, RD suppressed the inducibility of AF in a rabbit model for pressure associated atrial fibrosis, potentially by modulating renin-angiotensin-aldosterone system and decreasing pro-fibrotic factors

  18. Renal Denervation Suppresses the Inducibility of Atrial Fibrillation in a Rabbit Model for Atrial Fibrosis

    PubMed Central

    Zhou, Genqing; Chen, Songwen; Ouyang, Ping; Liu, Shaowen

    2016-01-01

    Renal denervation (RD) was reported to reduce the susceptibility of atrial fibrillation (AF), but the underlying mechanism has not been well understood. This study was performed to investigate the effect of RD on the inducibility of AF in a rabbit model for atrial fibrosis and to explore the potential mechanisms. Thirty-five rabbits were randomly assigned into sham-operated group (n = 12), abdominal aortic constriction (AAC) group (n = 12) and AAC with RD (AAC-RD) group (n = 11). The incidence of AF induced by burst pacing in atriums was determined. Blood was collected to measure the levels of rennin, angiotensin II and aldosterone. Atrial samples were preserved to evaluate protein and gene expression of collagen, connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1). Our data suggested cardiac structure remodeling and atrial fibrosis were successfully induced by AAC. Compared with the AAC group, the AAC-RD rabbits had smaller ascending aortic diameter and left ventricular end-systolic diameter. For burst pacing at the left atrium (LA), AF was induced in two of the 12 rabbits in the sham-operated group, 10 of the 12 rabbits in the AAC group, and 2 of the 11 rabbits in the AAC-RD group, with great difference among the three groups (P = 0.001). The percentage of LA burst stimulations with induced AF achieved 47.2% in the AAC group, which was higher than those in both the AAC-RD (12.1%) and the Sham-operated (5.6%) groups. Significantly increasing intercellular space in the AAC group (P<0.001) compared with the sham-operated rabbits. RD clearly decreased the volume fraction of collagen in LA and right atrium compared with that of the AAC group (P< 0.01). AAC-induced elevation of collagen I, CTGF and TGF-β1 was suppressed by RD. In conclusion, RD suppressed the inducibility of AF in a rabbit model for pressure associated atrial fibrosis, potentially by modulating renin-angiotensin-aldosterone system and decreasing pro-fibrotic factors

  19. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  20. High fat diet induces obesity in British Angora rabbit: a model for experimental obesity.

    PubMed

    Dhungel, S; Sinha, R; Sinha, M; Paudel, B H; Bhattacharya, N; Mandal, M B

    2009-01-01

    A reliable and cost-effective animal model for human obesity with its manifested disorders is yet to be established in the context of increased morbidity and mortality due to obesity and its related problems. Therefore, an attempt was made to produce obesity in locally available British Angora Rabbits (BAR) and examine the effect on metabolic and cardiovascular parameters. Adult male BARs weighing nearly 2 kg were randomly divided into two groups, one of the groups was fed with high fat diet (HFD) ad libitum for 10 weeks and the control group received standard normal rabbit chow for same period. Body weight, skinfold thickness, serum cholesterol, serum glucose and resting heart rate were measured before and after the dietary regimens. After 10 weeks, HFD group of rabbits demonstrated significant (P < 0.05) increase in body weight (+24%) and skinfold thickness (+37%). The gain in body weight was positively correlated to skinfold thickness (r = 0.61). Serum cholesterol, serum glucose and resting heart rate were also increased by 46%, 52% and 15%, respectively. Whereas no such increases in any of these parameters were observed in control group of rabbits. Our results suggest that obesity can be produced in BARs by feeding HFD. The obesity manifests with cardiovascular and metabolic changes. It is proposed that this may serve as a valid and reliable model of experimental obesity. PMID:19810577

  1. Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

    PubMed Central

    Liang, Xin-Mei; Tang, Guang-Yu; Cheng, Ying-Sheng; Zhou, Bi

    2009-01-01

    AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma. PMID:19418587

  2. A new rabbit model of implant-related biofilm infection: development and evaluation

    NASA Astrophysics Data System (ADS)

    Chu, Cheng-Bing; Zeng, Hong; Shen, Ding-Xia; Wang, Hui; Wang, Ji-Fang; Cui, Fu-Zhai

    2016-03-01

    This study is to establish a rabbit model for human prosthetic joint infection and biofilm formation. Thirty-two healthy adult rabbits were randomly divided into four groups and implanted with stainless steel screws and ultra-high molecular weight polyethylene (UHMWPE) washers in the non-articular surface of the femoral lateral condyle of the right hind knees. The rabbit knee joints were inoculated with 1 mL saline containing 0, 102, 103, 104 CFU of Staphylococcus epidermidis ( S. epidermidis) isolated from the patient with total knee arthroplasty (TKA) infection, respectively. On the 14th postoperative day, the UHMWPE washers from the optimal 103 CFU group were further examined. The SEM examination showed a typical biofilm construction that circular S. epidermidis were embedded in a mucous-like matrix. In addition, the LCSM examination showed that the biofilm consisted of the polysaccharide stained bright green fluorescence and S. epidermidis radiating red fluorescence. Thus, we successfully create a rabbit model for prosthetic joint infection and biofilm formation, which should be valuable for biofilm studies.

  3. Hierarchical spatial models for predicting pygmy rabbit distribution and relative abundance

    USGS Publications Warehouse

    Wilson, T.L.; Odei, J.B.; Hooten, M.B.; Edwards, T.C., Jr.

    2010-01-01

    Conservationists routinely use species distribution models to plan conservation, restoration and development actions, while ecologists use them to infer process from pattern. These models tend to work well for common or easily observable species, but are of limited utility for rare and cryptic species. This may be because honest accounting of known observation bias and spatial autocorrelation are rarely included, thereby limiting statistical inference of resulting distribution maps. We specified and implemented a spatially explicit Bayesian hierarchical model for a cryptic mammal species (pygmy rabbit Brachylagus idahoensis). Our approach used two levels of indirect sign that are naturally hierarchical (burrows and faecal pellets) to build a model that allows for inference on regression coefficients as well as spatially explicit model parameters. We also produced maps of rabbit distribution (occupied burrows) and relative abundance (number of burrows expected to be occupied by pygmy rabbits). The model demonstrated statistically rigorous spatial prediction by including spatial autocorrelation and measurement uncertainty. We demonstrated flexibility of our modelling framework by depicting probabilistic distribution predictions using different assumptions of pygmy rabbit habitat requirements. Spatial representations of the variance of posterior predictive distributions were obtained to evaluate heterogeneity in model fit across the spatial domain. Leave-one-out cross-validation was conducted to evaluate the overall model fit. Synthesis and applications. Our method draws on the strengths of previous work, thereby bridging and extending two active areas of ecological research: species distribution models and multi-state occupancy modelling. Our framework can be extended to encompass both larger extents and other species for which direct estimation of abundance is difficult. ?? 2010 The Authors. Journal compilation ?? 2010 British Ecological Society.

  4. Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models.

    PubMed

    Romero, Lucía; Carbonell, Beatriz; Trenor, Beatriz; Rodríguez, Blanca; Saiz, Javier; Ferrero, José M

    2011-10-01

    Several mathematical models of rabbit ventricular action potential (AP) have been proposed to investigate mechanisms of arrhythmias and excitation-contraction coupling. Our study aims at systematically characterizing how ionic current properties modulate the main cellular biomarkers of arrhythmic risk using two widely-used rabbit ventricular models, and comparing simulation results using the two models with experimental data available for rabbit. A sensitivity analysis of AP properties, Ca²⁺ and Na⁺ dynamics, and their rate dependence to variations (±15% and ±30%) in the main transmembrane current conductances and kinetics was performed using the Shannon et al. (2004) and the Mahajan et al. (2008a,b) AP rabbit models. The effects of severe transmembrane current blocks (up to 100%) on steady-state AP and calcium transients, and AP duration (APD) restitution curves were also simulated using both models. Our simulations show that, in both virtual rabbit cardiomyocytes, APD is significantly modified by most repolarization currents, AP triangulation is regulated mostly by the inward rectifier K⁺ current (I(K1)) whereas APD rate adaptation as well as [Na⁺](i) rate dependence is influenced by the Na⁺/K⁺ pump current (I(NaK)). In addition, steady-state [Ca²⁺](i) levels, APD restitution properties and [Ca²⁺](i) rate dependence are strongly dependent on I(NaK), the L-Type Ca²⁺ current (I(CaL)) and the Na⁺/Ca²⁺ exchanger current (I(NaCa)), although the relative role of these currents is markedly model dependent. Furthermore, our results show that simulations using both models agree with many experimentally-reported electrophysiological characteristics. However, our study shows that the Shannon et al. model mimics rabbit electrophysiology more accurately at normal pacing rates, whereas Mahajan et al. model behaves more appropriately at faster rates. Our results reinforce the usefulness of sensitivity analysis for further understanding of cellular

  5. Relation between the development of osteoporosis and osteonecrosis following glucocorticoid in a rabbit model

    PubMed Central

    Lin, Tao; Liu, Junbin; Yang, Shuhua; Liu, Xianzhe; Feng, Xiaobo; Fu, Dehao

    2016-01-01

    Background: There has been a recent increase in the number of patients suffering from bone and joint diseases, as a consequence of corticosteroids administration. There are more patients treated with low dose of GCs under long-term conditions in clinical, such as effect of GCs on Rheumatoid arthritis, Crohn's disease and Asthma patients. Hence, it was difficult for doctor to determine which problem occur first – OP or ON; however, there was no clinical report previously in the literature, and there was no effective animal model of OP and ON about low dose GCs. This study was conducted to develop rabbit models of glucocorticoid (GC)-induced femoral head ON and OP and to investigate the temporal relationship between the occurrence of the two events following administration of glucocorticoids. Materials and Methods: Fifty six, 6 months old female rabbits were randomly divided into the GC group and control group (C). Rabbits received gluteal injections of methylprednisolone sodium succinate once a day for 4 weeks, while normal saline solution in the control group. Rabbits were sacrificed at 0, 2, 4, and 8 weeks. Hip magnetic resonance imaging was performed before the rabbits were sacrificed. Serum calcium (Ca), phosphorus (P), total cholesterol, and triglyceride levels were also measured. The bone mineral density (BMD) of femoral head and the femoral shaft were measured by dual-energy X-ray absorptiometry. The trabecular parameters of the femur and the 4th lumbar vertebrae (L4) were measured with a micro-computed tomography (μ-CT). Also, the femoral head was stained with hematoxylin-eosin staining. Results: At 4 weeks in the GC group, the BMD of the femur reduced 33% and 22% in the femoral head and shaft; there was irregular intermediate to high T2-weighted images signals; μ-CT showed microfractures and cystic changes in the femoral head and L4 at 4 weeks. At 8 weeks in the GC group, the classical “line-like sign” indicating ON of the femoral head was observed

  6. Rabbit-Specific Ventricular Model of Cardiac Electrophysiological Function including Specialized Conduction System

    PubMed Central

    Bordas, R.; Gillow, K.; Lou, Q.; Efimov, I. R.; Gavaghan, D.; Kohl, P.; Grau, V.; Rodriguez, B.

    2011-01-01

    The function of the ventricular specialized conduction system in the heart is to ensure the coordinated electrical activation of the ventricles. It is therefore critical to the overall function of the heart, and has also been implicated as an important player in various diseases, including lethal ventricular arrhythmias such as ventricular fibrillation and drug-induced torsades de pointes. However, current ventricular models of electrophysiology usually ignore, or include highly simplified representations of the specialized conduction system. Here, we describe the development of a image-based, species-consistent, anatomically-detailed model of rabbit ventricular electrophysiology that incorporates a detailed description of the free-running part of the specialized conduction system. Techniques used for the construction of the geometrical model of the specialized conduction system from a magnetic resonance dataset and integration of the system model into a ventricular anatomical model, developed from the same dataset, are described. Computer simulations of rabbit ventricular electrophysiology are conducted using the novel anatomical model and rabbit-specific membrane kinetics to investigate the importance of the components and properties of the conduction system in determining ventricular function under physiological conditions. Simulation results are compared to panoramic optical mapping experiments for model validation and results interpretation. Full access is provided to the anatomical models developed in this study. PMID:21672547

  7. Cartilage changes link retrognathic mandibular growth to TMJ disc displacement in a rabbit model.

    PubMed

    Bryndahl, F; Warfvinge, G; Eriksson, L; Isberg, A

    2011-06-01

    Recent experimental research demonstrated that non-reducing temporomandibular joint (TMJ) disc displacement in growing rabbits impaired mandibular growth. TMJ disc displacement is also shown to induce histological changes of the condylar cartilage. The authors hypothesized that the severity of these changes would correlate to the magnitude of mandibular growth. Bilateral non-reducing TMJ disc displacement was surgically created in 10 growing New Zealand White rabbits. Ten additional rabbits constituted a sham operated control group. Aided by tantalum implants, growth was cephalometrically determined for each mandibular side during a period equivalent to childhood and adolescence in man. At the end of the growth period, histologically classified cartilage features were correlated with the assessed ipsilateral mandibular growth. Non-reducing displacement of the TMJ disc during the growth period induced histological reactions of the condylar cartilage in the rabbit model. The severity of cartilage changes was inversely correlated to the magnitude and the direction of mandibular growth, which resulted in a retrognathic growth pattern. PMID:21334177

  8. CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

    PubMed Central

    Kumar, Parveen; Kumar, Rakesh; Manuja, Balvinder Kumar; Singha, Harisankar; Sharma, Anshu; Virmani, Nitin; Yadav, Suresh Chandra; Manuja, Anju

    2015-01-01

    CpG oligodeoxynucleotides (CpG-ODN) stimulate immune cells from a wide spectrum of mammalian species. Class C CpG-ODN is relatively stable and has the combined immune effects of both A and B classes of CpG-ODN. Trypanosoma evansi produces the state of immuno-suppression in the infected hosts. The current chemotherapeutic agents against this parasite are limited in number and usually associated with severe side effects. The present work aimed to determine the immunostimulatory effects of CpG-ODN class C in T. evansi infected rabbits. Rabbits inoculated with CpG C and challenged with T. evansi resulted in delayed onset of clinical signs with reduced severity in comparison to that of T. evansi infected rabbits. The treatment also enhanced humoral immune responses. Histopathological findings in liver and spleen revealed enhancement of mononuclear cell infiltration and secondary B cell follicles. These results demonstrate that CpG-ODN class C, has immunostimulatory properties in rabbit model of trypanosomosis. The use of booster doses or sustained delivery of CpG-ODN will further elucidate the prolonged CpG-ODN generated immune responses. PMID:26039713

  9. Efficacy of gallium maltolate against Lawsonia intracellularis infection in a rabbit model.

    PubMed

    Sampieri, F; Allen, A L; Alcorn, J; Clark, C R; Vannucci, F A; Pusterla, N; Mapes, S M; Ball, K R; Dowling, P M; Thompson, J; Bernstein, L R; Gebhart, C J; Hamilton, D L

    2014-12-01

    Antimicrobial efficacy against Lawsonia intracellularis is difficult to evaluate in vitro, thus, the effects of gallium maltolate's (GaM) were investigated in a rabbit model for equine proliferative enteropathy (EPE). Juvenile (5-6-week-old) does were infected with 3.0 × 10(8) L. intracellularis/rabbit and allocated into three groups (n = 8). One week postinfection, one group was treated with GaM, 50 mg/kg; one, with doxycycline, 5 mg/kg; and one with a sham-treatment (control). Feces and blood were collected daily and weekly, respectively, to verify presence of L. intracellularis fecal shedding using qPCR, and seroconversion using immunoperoxidase monolayer assay. Rabbits were sacrificed after 1 week of treatment to collect intestinal tissues focusing on EPE-affected sections. Intestinal lesions were confirmed via immunohistochemistry. No difference was noted between treatments regarding EPE-lesions in jejunum (P = 0.51), ileum (P = 0.74), and cecum (P = 0.35), or in L. intracellularis fecal shedding (P = 0.64). GaM and doxycycline appear to have similar efficacy against EPE in infected rabbits. PMID:24730377

  10. Ketamine attenuates osteoarthritis of the knee via modulation of inflammatory responses in a rabbit model

    PubMed Central

    LU, WEI; WANG, LIN; WO, CHUNXIN; YAO, JING

    2016-01-01

    The aim of the present study was to investigate the efficacy of ketamine in attenuating osteoarthritis (OA) and modulating the expression of inflammatory mediators. A rabbit OA model was established by knee immobilization using plaster bandages. After six weeks, rabbits were randomly allocated into four groups (n=6/group): Normal saline, Ket60, Ket100, and Ket200 and twice a week for four weeks the rabbits received an intra-articular injection of saline, or 60, 100 or 200 µmol/l ketamine, respectively. One week after the final injection, samples of synovial membrane, synovial fluid and articular cartilage were isolated. The pathological changes were assessed by general observation, hematoxylin and eosin staining and Alcian blue/periodic-acid Schiff staining. Cartilage pathology was assessed using Mankin's scoring system. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 levels in the synovial fluid were measured by enzyme-linked immunosorbent assays. The nuclear factor (NF)-κB p65 subunit expression level in cartilage samples was determined by immunohistochemistry. OA was characterized by morphological changes in the articular surface, cartilage lesions, infiltration of inflammatory cells and a significantly increased Mankin's score. Elevated TNF-α and reduced IL-10 levels in the synovial fluid, along with increased p65 expression levels in the cartilage were observed in OA rabbits. Intra-articular injection of ketamine ameliorated the pathological characteristics of OA, reduced the Mankin's score, decreased TNF-α and NF-κB p65 expression levels, and increased the level of IL-10 expression in a dose-dependent manner. Thus is was demonstrated that Ketamine suppresses the inflammatory response in OA by modulating inflammatory mediator expression levels in a rabbit model of OA. PMID:27109206

  11. Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis

    PubMed Central

    Olson, J. Casey; Takahashi, Ayuko; Glotzbecker, Michael P.; Snyder, Brian D.

    2015-01-01

    Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have

  12. Molecular events linking cholesterol to Alzheimer's disease and inclusion body myositis in a rabbit model.

    PubMed

    Liu, Qing Yan; Koukiekolo, Roger; Zhang, Dong Ling; Smith, Brandon; Ly, Dao; Lei, Joy X; Ghribi, Othman

    2016-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by cognitive impairment and dementia, resulting from progressive synaptic dysfunction, loss and neuronal cell death. Inclusion body myositis (IBM) is a skeletal muscle degenerative disease, displaying progressive proximal and distal muscle weakness, in association with muscle fiber atrophy, degeneration and death. Studies have shown that the late onset version of AD (LOAD) and sporadic IBM (sIBM) in muscle share many pathological features, including the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins. High blood cholesterol is suggested to be a risk factor for LOAD. Many neuropathological changes of LOAD can be reproduced by feeding rabbits a 2% enriched cholesterol diet for 12 weeks. The cholesterol fed rabbit model also simultaneously develops sIBM like pathology, which makes it an ideal model to study the molecular mechanisms common to the development of both diseases. In the present study, we determined the changes of gene expression in rabbit brain and muscle during the progression of LOAD and sIBM pathology using a custom rabbit nucleotide microarray, followed by qRT-PCR analyses. Out of 869 unique transcripts screened, 47 genes showed differential expression between the control and the cholesterol-treated group during the 12 week period and 19 changed transcripts appeared to be common to LOAD and sIBM. The most notable changes are the upregulation of the hemoglobin gene family and the downregulation of the genes required for mitochondrial oxidative phosphorylation in both brain and muscle tissues throughout the time course. The significant overlap on the changes of gene expression in the brain and muscle of rabbits fed with cholesterol-enriched diet supports the notion that LOAD and sIBM may share a common etiology. PMID:27073745

  13. Ketamine attenuates osteoarthritis of the knee via modulation of inflammatory responses in a rabbit model.

    PubMed

    Lu, Wei; Wang, Lin; Wo, Chunxin; Yao, Jing

    2016-06-01

    The aim of the present study was to investigate the efficacy of ketamine in attenuating osteoarthritis (OA) and modulating the expression of inflammatory mediators. A rabbit OA model was established by knee immobilization using plaster bandages. After six weeks, rabbits were randomly allocated into four groups (n=6/group): Normal saline, Ket60, Ket100, and Ket200 and twice a week for four weeks the rabbits received an intra‑articular injection of saline, or 60, 100 or 200 µmol/l ketamine, respectively. One week after the final injection, samples of synovial membrane, synovial fluid and articular cartilage were isolated. The pathological changes were assessed by general observation, hematoxylin and eosin staining and Alcian blue/periodic‑acid Schiff staining. Cartilage pathology was assessed using Mankin's scoring system. Tumor necrosis factor (TNF)‑α and interleukin (IL)‑10 levels in the synovial fluid were measured by enzyme‑linked immunosorbent assays. The nuclear factor (NF)‑κB p65 subunit expression level in cartilage samples was determined by immunohistochemistry. OA was characterized by morphological changes in the articular surface, cartilage lesions, infiltration of inflammatory cells and a significantly increased Mankin's score. Elevated TNF‑α and reduced IL-10 levels in the synovial fluid, along with increased p65 expression levels in the cartilage were observed in OA rabbits. Intra‑articular injection of ketamine ameliorated the pathological characteristics of OA, reduced the Mankin's score, decreased TNF‑α and NF‑κB p65 expression levels, and increased the level of IL‑10 expression in a dose-dependent manner. Thus is was demonstrated that Ketamine suppresses the inflammatory response in OA by modulating inflammatory mediator expression levels in a rabbit model of OA. PMID:27109206

  14. Congestive heart failure model in rabbits: effects of digoxin and a drug containing toad venom.

    PubMed

    Morishita, S; Shoji, M; Oguni, Y; Ito, C; Noguchi, K; Sakanashi, M

    1991-08-01

    A low-output-type heart failure model was established in rabbits by protease treatment of the surface of the left ventricular anterior wall. Heart rate, aortic blood flow (AoF), left ventricular pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and mean blood pressure (MBP) remained at a normal level. Intraduodenal administration of digoxin and a drug containing toad venom (Kyushin:KY) improved the hemodynamic parameters by increasing the AoF, LVP and max dP/dt and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of digoxin and KY on this heart failure model originate from their cardiotonic activity. PMID:1744986

  15. Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model

    PubMed Central

    Zhai, Ji-Liang; Weng, Xi-Sheng; Wu, Zhi-Hong; Guo, Shi-Gong

    2016-01-01

    Background: Prevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits. Methods: Seventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated. Results: The PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group. Conclusions: Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular

  16. Experimental research of Fuaile medical adhesive for portal vein embolization in white rabbit models

    PubMed Central

    JIANG, TIANPENG; WANG, LIZHOU; LI, XING; SONG, JIE; WU, XIAOPING; AN, TIANZHI; ZHOU, SHI

    2015-01-01

    The aim of the present study was to investigate the feasibility and efficacy of Fuaile medical adhesive for portal vein embolization in the treatment of a rabbit model. This study used 26 white rabbits, 14 of which were selected and assigned into seven groups (n=2) for the preliminary experiment. Fuaile medical adhesive was mixed with lipiodol at different ratios of 1:0, 1:1, 1:2, 1:3, 1:4, 1:5 and 0:1, respectively, and administered via the portal trunk. The remaining 12 white rabbits were randomly divided into two groups (n=6). The evaluation of the results included the degree of adhesion to the vessels, the extent of embolization and the reaction of the rabbit. Hepatic and renal functions were detected prior to and at 1, 7 and 14 days post-embolization, respectively. Angiography, CT scans and pathological examinations were conducted at post-embolization. Histological examinations revealed that the topical swollen lesions were darker. Light microscopy showed embolic agents in the portal venous blood vessels and the formation of a secondary thrombus. Hepatic necrosis appeared surrounding the embolization area. Inflammatory cell infiltration of different degrees occurred in the early stage and inflammatory fibroplasia occurred in the late stage. Alanine aminotransferase and aspartate aminotransferase levels increased at 1 day post-embolization, peaked at 7 days and was in the normal range at 14 days. The levels of blood urea nitrogen and ceruloplasmin were elevated at 1 day post-embolization and lowered to normal at 7 days. Fuaile medical adhesive is an effective, safe and inexpensive agent, used for effectively inducing embolization in the portal trunk, and the first and second branches of rabbit portal veins. The use of Fuaile therefore merits widespread application in clinical practice. PMID:26137115

  17. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

    PubMed

    Komissarov, Andrey A; Florova, Galina; Azghani, Ali O; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-08-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

  18. Effects of Noscarna™ on hypertrophic scarring in the rabbit ear model: histopathological aspects.

    PubMed

    Lee, Dong Won; Ku, Sae Kwang; Cho, Hyuk Jun; Kim, Jeong Hwan; Hiep, Tran Tuan; Han, Sang Duk; Kim, Bo Gyun; Kang, Min Kyung; Do, Eui Seon; Jun, Joon Ho; Jang, Sun Woo; Son, Mi-Won; Sohn, Young Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2012-11-01

    In this study, we evaluated the effects of silicone-based gel on the healing of hypertrophic scars in the rabbit ear model. After 4-week application of silicone-based gel containing allantoin, dexpanthenol and heparin (Noscarna™) to scars in a rabbit ear model of hypertrophic scarring, significant improvements in hypertrophic scar healing and a great loss of skin pigment were observed compared to the non-treated control, base or silicone control-treated scars. Furthermore, histological analysis of Noscarna™-treated scars revealed a significant reduction in scar elevation index (SEI), anterior skin and epithelial thicknesses, inflammatory cells, vessels, collagen disorganization and fibroblasts compared to all control hypertrophic scars. Furthermore, Noscarna™ showed more favorable effects on hypertrophic scars than a commercial product, Contractubex®. Therefore, these results clearly demonstrated that the newly developed silicone-based gel, Noscarna™, could be a promising formulation as an effective therapeutic agent for hypertrophic scars. PMID:23212642

  19. Analysis of host range restriction determinants in the rabbit model: comparison of homologous and heterologous rotavirus infections.

    PubMed

    Ciarlet, M; Estes, M K; Barone, C; Ramig, R F; Conner, M E

    1998-03-01

    The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV x D (G1), RRV x DS-1 (G2), and RRV x ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 10(3) 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction

  20. Protective cell-mediated immunity by DNA vaccination against Papillomavirus L1 capsid protein in the Cottontail Rabbit Papillomavirus model.

    PubMed

    Hu, Jiafen; Cladel, Nancy M; Budgeon, Lynn R; Reed, Cynthia A; Pickel, Martin D; Christensen, Neil D

    2006-01-01

    Papillomavirus major capsid protein L1 has successfully stimulated protective immunity against virus infection by induction of neutralizing antibodies in animal models and in clinical trials. However, the potential impact of L1-induced protective cell-mediated immune (CMI) responses is difficult to measure in vivo because of the coincidence of anti-L1 antibody. In this study, we tested the hypothesis that L1 could activate CMI, using the Cottontail Rabbit Papillomavirus (CRPV)-rabbit model. A unique property of this model is that infections can be initiated with viral DNA, thus bypassing all contributions to protection via neutralizing anti-L1 antibody. DNA vaccines containing either CRPV L1, or subfragments of L1 (amino-terminal two-thirds of L1 [L1N] and the carboxylterminal two-thirds of L1 [L1C]), were delivered intracutaneously into rabbits, using a gene gun. After three booster immunizations, the rabbits were challenged with several viral DNA constructs: wild-type CRPV, CRPV L1ATGko (an L1 ATG knockout mutation), and CRPV-ROPV hybrid (CRPV with a replacement L1 from Rabbit Oral Papillomavirus). Challenge of L1 DNA-vaccinated rabbits with wild-type CRPV resulted in significantly fewer papillomas when compared with challenge with CRPV L1ATGko DNA. Significantly smaller papillomas were found in CRPV L1-, L1N-, and L1C-vaccinated rabbits. In addition, rabbits vaccinated with either L1 or L1N grew significantly fewer and smaller papillomas when challenged with CRPV-ROPV hybrid DNA. Therefore, CRPV L1 DNA vaccination induced CMI responses to CRPV DNA infections that can contribute to protective immunity. Cross-protective immunity against CRPV L1 and ROPV L1 was elicited in these CRPV L1- and subfragment-vaccinated rabbits. PMID:16987067

  1. Development and hemocompatibility testing of nitric oxide releasing polymers using a rabbit model of thrombogenicity

    PubMed Central

    Major, Terry C; Handa, Hitesh; Annich, Gail M; Bartlett, Robert H

    2014-01-01

    Hemocompatibility is the goal for any biomaterial contained in extracorporeal life supporting (ECLS) medical devices. The hallmarks for hemocompatibility include nonthrombogenicity, platelet preservation and maintained platelet function. Both in vitro and in vivo assays testing for compatibility of the blood/biomaterial interface have been used over the last several decades to ascertain if the biomaterial used in medical tubing and devices will require systemic anticoagulation for viability. Over the last 50 years systemic anticoagulation with heparin has been the gold standard in maintaining effective ECLS. However, the biomaterial that maintains effective ECLS without the use of any systemic anticoagulant has remained elusive. In this review, the in vivo 4-h rabbit thrombogenicity model genesis will be described with emphasis on biomaterials that may require no systemic anticoagulation for ECLS longevity. These novel biomaterials may improve extracorporeal circulation (ECC) hemocompatibility by preserving near resting physiology of the major blood components, the platelets and monocytes. The rabbit ECC model provides a complete assessment of biomaterial interactions with the intrinsic coagulation players, the circulating platelet and monocytes. This total picture of blood/biomaterial interaction suggests that this rabbit thrombogenicity model could provide a standardization for biomaterial hemocompatibility testing. PMID:24934500

  2. Pathogenicity of Prevotella intermedia and Prevotella nigrescens isolates in a wound chamber model in rabbits.

    PubMed

    Hafström, C; Dahlén, G

    1997-06-01

    The pathogenicity of 14 isolates identified as Prevotella intermedia or Prevotella nigrescens by serogrouping using monoclonal antibodies was compared in a tissue cage model in rabbits. Seven strains from periodontal abscesses, 5 strains from deep periodontal pockets and 2 strains from gingivitis were tested in the animal model comprising 6 Teflon tissue cages implanted on the back each of 34 rabbits. A total of 10(5)-10(8) cells of P. intermedia or P. nigrescens strains were inoculated alone or together with either Actinobacillus actinomycetemcomitans or Streptococcus mitis. Five strains of Porphyromonas gingivalis were used as a reference. The infectivity was recorded as pus formation and log viable count in aspirated material for 3, 7 and 14 days. None of the Prevotella strains inoculated in monoculture survived more than 3 days, and they had no capacity to produce abscess. P. intermedia or P. nigrescens strains in combination with A. actinomycetemcomitans produced abscesses in 33-100% and with S. mitis in 42-100%. No difference in abscess formation or log viable count in samples after 14 days was recorded between serogroup I (P. intermedia) and serogroup II and III (P. nigrescens). The infectivity of P. intermedia or P. nigresceas strains did not differ whether they were isolated from periodontal abscess, periodontal pocket or gingivitis. P. intermedia and P. nigrescens strains produced abscesses in combination with a facultative anaerobic strain and appears to have a similar pathogenicity in the wound chamber model in rabbits. PMID:9467400

  3. Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

    PubMed Central

    Sohn, Sung-Keun; Kim, Kyung-Taek; Kim, Chul-Hong; Ahn, Hee-Bae; Rho, Mee-Sook; Jeong, Min-Ho; Sun, Sang-Kyu

    2010-01-01

    Background The aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study. Methods Ten rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting. Results The HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p < 0.05). On comparing the change of bone mineral density the bone ingrowth surface area among the 4 groups, there were no statistically significant differences among the groups found for any period (p > 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged. Conclusions We concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite

  4. Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits

    PubMed Central

    Gahukamble, Abhay Deodas; McDowell, Andrew; Post, Virginia; Salavarrieta Varela, Julian; Rochford, Edward Thomas James; Richards, Robert Geoff; Patrick, Sheila

    2014-01-01

    Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an “aseptically failed” prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as “aseptic” failure. PMID:24599975

  5. PTH increases jaw mineral density in a rabbit model of osteoporosis.

    PubMed

    Bellido, M; Lugo, L; Castañeda, S; Roman-Blas, J A; Rufián-Henares, J A; Navarro-Alarcón, M; Largo, R; Herrero-Beaumont, G

    2010-04-01

    Intermittent parathyroid hormone (PTH) administration has been shown to be a promising therapy for systemic bone loss. Accordingly, we hypothesized that PTH could have positive results in treating oral complications of osteoporosis. Hence, we evaluated both mandibular bone loss and its response to PTH in a rabbit model of osteoporosis induced by ovariectomy and glucocorticoid administration. There was a significant and marked decrease in bone mineral density (BMD), bone mineral content (BMC), and calcium content in ash from the osteoporotic peri-alveolar region, which influenced global jaw loss. Remarkably, PTH (1-34) administration to osteoporotic rabbits almost completely reversed BMD, BMC, and calcium content fall in the peri-alveolar region, subsequently reducing global mandibular bone loss. Thus, although the peri-alveolar region is particularly susceptible to osteoporosis, it also responds well to intermittent PTH. Therefore, these results suggest that PTH might represent a valid therapy for improving the osseointegration of dental implants in persons with osteoporosis. PMID:20177133

  6. Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model

    PubMed Central

    Wang, Mengmeng

    2015-01-01

    Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis. Methods. Fifteen rabbits were randomly divided into five groups. Group A (n = 3) is the control group. The right eyes of animals in Groups B,C, D, and E (n = 3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group. Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P < 0.05) and in Groups C, D, and E at 14 d postoperatively (P < 0.05). Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment. PMID:26509077

  7. A New Ischemic Model Using a Radiofrequency Wire Electrode in a Rabbit Hindlimb

    SciTech Connect

    Baik, Hye Won Kwak, Byung Kook; Shim, Hyung Jin; Kim, Yang Soo; Lee, Jong Beom; Kim, Kun Sang

    2008-07-15

    The purpose of this study was to establish an ischemic rabbit hindlimb model using a radiofrequency (RF) wire electrode. We inserted a polytetrafluoroethylene-coated wire with a 2-cm exposed tip into the left superficial femoral artery of seven New Zealand white rabbits and performed RF ablation (RFA) while pulling the wire back. We assessed the clinical findings, angiography, computed tomography perfusion, and permeability surface until 6 weeks after RFA. The angiography demonstrated complete obstruction from the proximal external iliac artery to the distal superficial femoral artery and showed a gradual increment in the angiogenic score, which represents the degree of angiogenesis (r = 0.86, p < 0.0001). The left-to-right ratios of the computed tomography perfusion and permeability surface were significantly reduced after 4 days (p < 0.05), and then they gradually increased with time. We conclude that endovascular RFA using an RF wire electrode is a reproducible and measurable way to create an ischemic rabbit hindlimb model.

  8. Curative Effects of Oleanolic Acid on Formed Hypertrophic Scars in the Rabbit Ear Model

    PubMed Central

    Zhang, Hong; Zhang, Yan; Jiang, Yi-Ping; Zhang, Lan-Ke; Peng, Cheng; He, Kun; Rahman, Khalid; Qin, Lu-Ping

    2012-01-01

    Hypertrophic scarring is a common proliferative disorder of dermal fibroblasts characterized by collagen overproduction and excessive deposition of extracellular matrix (ECM). There is no consensus about the best therapeutics to produce complete and permanent improvement of scars with few side effects. To investigate the therapeutic effects of oleanolic acid (OA) on hypertrophic scars and explore the possible mechanism of action involved, a rabbit ear model with hypertrophic scars was established. OA (2.5%, 5%, and 10%) was given once daily to the scars for 28 consecutive days. As a result, OA significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β1, MMP-1, TIMP-1, and collagens I and III were notably decreased, and the number of apoptosis cells and mRNA expression of MMP-2, caspase-3, and caspase-9 were markedly increased in the scar tissue. The scar elevation index (SEI) was also evidently reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that OA has the favorable curative effects on formed hypertrophic scars in the rabbit ear model, and the possible mechanism of action is that OA decreases HSFs proliferation and increases HSFs apoptosis by reduction of P311 gene expression and TGF-β1 production, inhibition of TIMP-1 secretion, enhancement of MMP-2 activity, and subsequently facilitation of degradation of collagen types I and III. PMID:23326292

  9. Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model

    PubMed Central

    Achermann, Yvonne; Tran, Bao; Kang, Misun; Harro, Janette M.

    2015-01-01

    Propionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implant-associated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes. PMID:25694647

  10. Subsynovial Connective Tissue is Sensitive to Surgical Interventions in a Rabbit Model of Carpal Tunnel Syndrome

    PubMed Central

    Sun, Yu-Long; Moriya, Tamami; Zhao, Chunfeng; Kirk, Ramona L.; Chikenji, Takako; Passe, Sandra M.; An, Kai-Nan; Amadio, Peter C.

    2011-01-01

    The most common histological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) in the tunnel. While the cause of SSCT fibrosis and the relationship of SSCT fibrosis and CTS are unknown, one hypothesis is that SSCT injury causes fibrosis, and that the fibrosis then leads to CTS. We investigated the sensitivity of the SSCT to injuries. Two types of surgical intervention were performed in a rabbit model: a skin incision with tendon laceration and SSCT stretching sufficient to damage the SSCT, and skin incision alone,. Twelve weeks after surgery, the rabbit carpal tunnel tissues were studied with immunochemistry for TGF-β receptors 1, 2, and 3, collagen III, and collagen VI. All TGF-β receptors were expressed. The percentages of the TGF-β receptors’ expressions were less in the control SSCT fibroblasts than in the fibroblasts from rabbits with surgical interventions. The surgical interventions did not result in any alteration of collagen III expression. However, both surgical interventions resulted in a significant decrease in collagen VI expression compared to the control group. The two surgical interventions achieved similar expression of TGF-β receptors and collagens. Our results provide evidence that the SSCT is sensitive to surgical interventions, even when these are modest. Since SSCT fibrosis is a hallmark of carpal tunnel syndrome, these data also suggest that such fibrosis could result from relatively minor trauma. PMID:22009518

  11. The Longitudinal Assessment of Osteomyelitis Development by Molecular Imaging in a Rabbit Model

    PubMed Central

    Odekerken, Jim C. E.; Walenkamp, Geert H. I. M.; Brans, Boudewijn T.; Welting, Tim J. M.; Arts, Jacobus J. C.

    2014-01-01

    Introduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. Methods. An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of  18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model. PMID:25295260

  12. Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis

    PubMed Central

    Yan, Zhao-wei; Dong, Ji; Qin, Chen-hao; Zhao, Chun-yang; Miao, Li-yan; He, Chun-yan

    2015-01-01

    Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra-articularly injected with CDCA (10 mg/kg or 50 mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. CDCA also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight CDCA might be a potential therapeutic agent for OA. PMID:26538834

  13. Pulmonary toxicity in a rabbit model of stereotactic lung radiation therapy: efficacy of a radioprotector.

    PubMed

    Mata, Jaime; Sheng, Ke; Hagspiel, Klaus; Ruppert, Kai; Sylvester, Peter; Mugler, John; Fernandes, Carolina; Guan, Steven; Larner, James; Read, Paul

    2014-08-01

    This study aimed to assess the efficacy of the radioprotector amifostine in limiting radiation toxicity in a rabbit model of lung stereotactic body radiation therapy (SBRT) by correlating contrast-enhanced magnetic resonance angiography (ce-MRA), computed tomography (CT), and helium-3 (He-3) magnetic resonance imaging (MRI) with histopathology. Multiple MRI techniques were tested to obtain complementing physiologic information. Thirteen rabbits received SBRT to the right lower lobe of the lung. Specifically, 4 received 3 × 11 Gray (Gy), 6 received 3 × 11 Gy and 50 mg/kg of amifostine pre-SRBT, and 3 received 3 × 7, 3 × 9, or 3 × 13 Gy. Imaging was performed at baseline and 4, 8, 12, and 16 weeks post-SBRT. Ce-MRA perfusion difference between lungs in the irradiated group at 16 weeks post-treatment was statistically significant (P = .04) whereas the difference in the irradiated + amifostine group was not (P = .30). Histologically observed low red blood cell (RBC) count and CT hypodensity suggests changes were primarily related to perfusion; however, structural changes, such as increased alveolar size, were also present. No changes in He-3 MRI lung ventilation were observed in either group. Although radiation-induced injury detected in rabbits as CT hypodensity contrasted with increased density observed in humans/rodents, the changes in ce-MRA and CT were still significantly reduced after the addition of amifostine to SBRT. Use of CT and selected MRI techniques helped to pinpoint primary physiologic changes. PMID:24926529

  14. The Effects of Irreversible Electroporation on the Achilles Tendon: An Experimental Study in a Rabbit Model

    PubMed Central

    Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    Background To evaluate the potential effects of irreversible electroporation ablation on the Achilles tendon in a rabbit model and to compare the histopathological and biomechanical changes between specimens following electroporation ablation and radiofrequency ablation. Methods A total of 140 six-month-old male New Zealand rabbits were used. The animals were randomly divided into two groups, 70 in the radiofrequency ablation group and 70 in the electroporation group. In situ ablations were applied directly to the Achilles tendons of rabbits using typical electroporation (1800 V/cm, 90 pulses) and radiofrequency ablation (power control mode) protocols. Histopathological and biomechanical evaluations were performed to examine the effects of electroporation ablation and radiofrequency ablation over time. Results Both electroporation and radiofrequency ablation produced complete cell ablation in the target region. Thermal damage resulted in tendon rupture 3 days post radiofrequency ablation. In contrast, electroporation-ablated Achilles tendons preserved their biomechanical properties and showed no detectable rupture at this time point. The electroporation-ablated tendons exhibited signs of recovery, including tenoblast regeneration and angiogenesis within 2 weeks, and the restoration of their integral structure was evident within 12 weeks. Conclusions When applying electroporation to ablate solid tumors, major advantage could be that collateral damage to adjacent tendons or ligaments is minimized due to the unique ability of electroporation ablation to target the cell membrane. This advantage could have a significant impact on the field of tumor ablation near vital tendons or ligaments. PMID:26114962

  15. Femoral head blood flow in long-term steroid therapy: study of rabbit model

    SciTech Connect

    Wang, G.J.; Hubbard, S.L.; Reger, S.I.; Miller, E.D.; Stamp, W.G.

    1983-12-01

    Using a rabbit model, previous studies showed steroid-induced hyperlipidemia with subsequent fatty embolization of the subchondral arteries and hypertrophy of the marrow fat cells, followed by elevation of femoral head pressure from the normal level of 25 cm to nearly 60 cm H2O after eight weeks of treatment. This has led us to believe that pressure changes lead to decreased blood flow in the femoral head. In our study of 22 New Zealand white adult rabbits, weighing an average of 4.0 kg, 14 received a weekly dose of 12.45 mg of methylprednisolone (Depo-Medrol), and eight served as control. Femoral head blood flow was established using the radioactive microsphere technique. Control and cortisone-treated rabbits had femoral head blood flow measured 6, 8 and 10 weeks after treatment. The average blood flow in the control femoral heads averaged 0.2039 +/- 0.076 ml/min/gm, with no difference in the left side and the right side. In the treated group, the average blood flow at ten weeks was 0.162 +/- 0.039 ml/min/gm on the right and 0.164 +/- 0.037 ml/min/gm on the left, which was significantly different. This is parallel to unpredictable clinical findings in human beings.

  16. Femoral head blood flow in long-term steroid therapy: study of rabbit model.

    PubMed

    Wang, G J; Hubbard, S L; Reger, S I; Miller, E D; Stamp, W G

    1983-12-01

    Using a rabbit model, previous studies showed steroid-induced hyperlipidemia with subsequent fatty embolization of the subchondral arteries and hypertrophy of the marrow fat cells, followed by elevation of femoral head pressure from the normal level of 25 cm to nearly 60 cm H2O after eight weeks of treatment. This has led us to believe that pressure changes lead to decreased blood flow in the femoral head. In our study of 22 New Zealand white adult rabbits, weighing an average of 4.0 kg, 14 received a weekly dose of 12.45 mg of methylprednisolone (Depo-Medrol), and eight served as control. Femoral head blood flow was established using the radioactive microsphere technique. Control and cortisone-treated rabbits had femoral head blood flow measured 6, 8 and 10 weeks after treatment. The average blood flow in the control femoral heads averaged 0.2039 +/- 0.076 ml/min/gm, with no difference in the left side and the right side. In the treated group, the average blood flow at ten weeks was 0.162 +/- 0.039 ml/min/gm on the right and 0.164 +/- 0.037 ml/min/gm on the left, which was significantly different. This is parallel to unpredictable clinical findings in human beings. PMID:6648615

  17. Modulation of Inflammatory and Profibrotic Signaling in a Rabbit Model of Acute Phonotrauma Using Triamcinolone

    PubMed Central

    Hall, Joseph E.; Suehiro, Atsushi; Branski, Ryan C.; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objective To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma. Study Design In vivo rabbit phonation model. Setting Academic medical center. Subjects and Methods Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 μg/25 μL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 μg/25 μL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)–1β, and transforming growth factor (TGF)–β1. Results Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P <.001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1β (P < .001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1β gene expression than control (6.30) (P = .001). There were no significant differences in IL-1β gene expression between treatment groups. There were no significant differences in TGF-β1 gene expression (P = .525) between treatment and control groups. Conclusion Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1β, and TGF-β1 gene transcript levels. PMID:22399283

  18. Mycobacterium avium Subspecies paratuberculosis Infection Modifies Gut Microbiota under Different Dietary Conditions in a Rabbit Model

    PubMed Central

    Arrazuria, Rakel; Elguezabal, Natalia; Juste, Ramon A.; Derakhshani, Hooman; Khafipour, Ehsan

    2016-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) the causative agent of paratuberculosis, produces a chronic granulomatous inflammation of the gastrointestinal tract of ruminants. It has been recently suggested that MAP infection may be associated with dysbiosis of intestinal microbiota in ruminants. Since diet is one of the key factors affecting the balance of microbial populations in the digestive tract, we intended to evaluate the effect of MAP infection in a rabbit model fed a regular or high fiber diet during challenge. The composition of microbiota of the cecal content and the sacculus rotundus was studied in 20 New Zealand white female rabbits. The extracted DNA was subjected to paired-end Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene for microbiota analysis. Microbial richness (Chao1) in the cecal content was significantly increased by MAP infection in regular diet rabbits (p = 0.0043) and marginally increased (p = 0.0503) in the high fiber group. Analysis of beta-diversity showed that MAP infection produces deeper changes in the microbiota of sacculus rotundus than in the cecal content. A lower abundance of Proteobacteria in the cecal content of infected animals fed the high fiber diet and also lower abundance of Bacteroidetes in the sacculus rotundus of infected animals fed the regular diet were observed. Based on OPLS-DA analysis, we observed that some bacteria repeatedly appear to be positively associated with infection in different samples under different diets (families Dehalobacteriaceae, Coriobacteriaceae, and Mogibacteriaceae; genus Anaerofustis). The same phenomenon was observed with some of the bacteria negatively associated with MAP infection (genera Anaerostipes and Coprobacillus). However, other groups of bacteria (Enterobacteriaceae family and ML615J-28 order) were positively associated with infection in some circumstances and negatively associated with infection in others. Data demonstrate that MAP infection

  19. Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model

    PubMed Central

    Soejima, T.; Murakami, H.; Noguchi, K.; Shiba, N.; Nagata, K.

    2016-01-01

    Objectives The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle. Materials and Methods Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle. Results At post-operative week 8, the distal end of the regenerated tissue reached the vicinity of the tibial insertion on the control side in two of six specimens. On the IG side, the regenerated tissue maintained continuity with the tibial insertion in all specimens. The cross-sectional area of the IG side was significantly greater than that of the control side. The proportion of fatty tissue in the semitendinosus muscle on the IG side was comparable with that of the control side, but was significantly greater than that of the normal muscle. Conclusions Tendon tissue regenerated with the fascia lata graft was thicker than naturally occurring regenerated tissue. However, the proportion of fatty tissue in the semitendinosus muscle was greater than that of normal muscle. Cite this article: K. Tabuchi, T. Soejima, H. Murakami, K. Noguchi, N. Shiba, K. Nagata. Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model. Bone Joint Res 2016;5:247–252. DOI: 10

  20. Accelerated 20-year sunlight exposure simulation of a photochromic foldable intraocular lens in a rabbit model

    PubMed Central

    Werner, Liliana; Abdel-Aziz, Salwa; Peck, Carolee Cutler; Monson, Bryan; Espandar, Ladan; Zaugg, Brian; Stringham, Jack; Wilcox, Chris; Mamalis, Nick

    2011-01-01

    PURPOSE To assess the long-term biocompatibility and photochromic stability of a new photochromic hydrophobic acrylic intraocular lens (IOL) under extended ultraviolet (UV) light exposure. SETTING John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN Experimental study. METHODS A Matrix Aurium photochromic IOL was implanted in right eyes and a Matrix Acrylic IOL without photochromic properties (n = 6) or a single-piece AcrySof Natural SN60AT (N = 5) IOL in left eyes of 11 New Zealand rabbits. The rabbits were exposed to a UV light source of 5 mW/cm2 for 3 hours during every 8-hour period, equivalent to 9 hours a day, and followed for up to 12 months. The photochromic changes were evaluated during slitlamp examination by shining a penlight UV source in the right eye. After the rabbits were humanely killed and the eyes enucleated, study and control IOLs were explanted and evaluated in vitro on UV exposure and studied histopathologically. RESULTS The photochromic IOL was as biocompatible as the control IOLs after 12 months under conditions simulating at least 20 years of UV exposure. In vitro evaluation confirmed the retained optical properties, with photochromic changes observed within 7 seconds of UV exposure. The rabbit eyes had clinical and histopathological changes expected in this model with a 12-month follow-up. CONCLUSIONS The new photochromic IOL turned yellow only on exposure to UV light. The photochromic changes were reversible, reproducible, and stable over time. The IOL was biocompatible with up to 12 months of accelerated UV exposure simulation. PMID:21241924

  1. Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

    PubMed

    Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

    2015-09-01

    The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p < 0.05), 62 were elevated and five decreased in ascending aortas from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring, which confirmed the iTRAQ results. Many of the observed protein changes are consistent with known molecular perturbations in the ascending aorta that occur in response to hypercholesterolemia, e.g. elevation of tissue levels of apolipoproteins, extracellular matrix adhesion proteins, glycolytic enzymes, heat shock proteins and proteins involved in immune defense. We also made a number of novel observations, including a 15-fold elevation of glycoprotein (trans-membrane) nmb-like (Gpnmb) in response to HCD. Gpnmb has previously been linked to angiogenesis but not to atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans. PMID:26232167

  2. A Chitosan-Based Sinus Sealant for Reduction of Adhesion Formation in Rabbit and Sheep Models

    PubMed Central

    Medina, Jennifer G.; Steinke, John W.; Das, Subinoy

    2013-01-01

    Objective Chronic sinusitis is the most prevalent chronic disease in the United States in adults aged 18 to 44 years, with approximately 250,000 operations performed annually. Although often successful, sinus surgery fails in greater than 15% of patients. Adhesion formation is a common complication and cause for subsequent revision surgery. Here, the authors evaluate a sprayable chitosan/starch-based sinus sealant and demonstrate its ability to reduce adhesion formation both in vitro and in 2 animal models. Study Design Randomized, controlled, animal trials. Setting Academic medical center (fibroblast experiments) and animal laboratories (sheep and rabbit studies). Subjects and Methods This sinus sealant was applied to human cultured fibroblasts obtained from surgically removed polyps to examine its ability to inhibit fibroblast migration and proliferation. The sinus sealant was applied to New Zealand White rabbits (n = 20) in an established cecal-sidewall abrasion model and to sheep (n = 10) in a sinus surgical adhesion model to examine its ability to reduce adhesion formation. Results This sinus sealant inhibited migration and proliferation of human cultured fibroblasts and reduced the total adhesion score from 4.9 to 0.3 for a total reduction of 94% (95th percentile confidence interval [CI], 78%, 100%; P < .001) in a well-established rabbit cecal-sidewall model commonly used for adhesion testing. Moreover, this sealant reduced adhesion formation from 80% to 10% for a total reduction of 70% (95th percentile CI, 57%, 93%; P = .003) in a sheep sinus adhesion surgical model. Conclusion This chitosan-based sealant demonstrates promise for reducing adhesion formation in sinus surgery. PMID:22492298

  3. Comparative Analysis of Methods to Induce Myocardial Infarction in a Closed-Chest Rabbit Model

    PubMed Central

    Isorni, Marc-Antoine; Casanova, Amaury; Piquet, Julie; Bellamy, Valérie; Pignon, Charly; Puymirat, Etienne; Menasche, Philippe

    2015-01-01

    Objective. To develop a rabbit model of closed-chest catheter-induced myocardial infarction. Background. Limitations of rodent and large animal models justify the search for clinically relevant alternatives. Methods. Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (n = 4), interlocking coils (n = 4), thrombogenic gelatin sponge (n = 4), balloon occlusion (n = 4), and alcohol injection (n = 8). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction. Results. The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically. Conclusions. By following a stepwise approach, a minimally invasive, effective, and reproducible

  4. Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis

    PubMed Central

    Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

    2015-01-01

    Objective We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis. Results In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index. Conclusion In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure. PMID:26090815

  5. A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. I. Synostotic onset, pathology, and sutural growth patterns.

    PubMed

    Mooney, M P; Siegel, M I; Burrows, A M; Smith, T D; Losken, H W; Dechant, J; Cooper, G; Kapucu, M R

    1998-06-01

    Poswillo has stated, "The more severe anomalies of the calvaria, such as plagiocephaly, Crouzon [syndrome], and Apert syndrome still defy explanation, in the absence of an appropriate animal system to study" (p. 207). This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis. Part 1 presents pathological findings and compensatory sutural growth data from 109 normal rabbits and 82 craniosynostotic rabbits from this colony. Synostotic foci, onset, and progression were described in the calvariae from 102 staged (fetal days 21, 25, 27, 33; term = 30 days) fetuses (39 normal, 63 synostosed). Calvarial suture growth patterns from 10 to 126 days of age were assessed from serial radiographs obtained from 89 rabbits (70 normal rabbits and 19 rabbits with unicoronal suture synostosis) with amalgam bone marker implants. Perinatal results revealed that by fetal day 25 the synostotic focal point in synostotic rabbits consistently originated from the endocortical surface of the calvaria in the middle of the coronal suture at a presumed high-tension, interdigitating zone. Histological analysis revealed hyperostotic osteogenic fronts on the affected side compared with the unaffected side. Postnatal sutural growth data revealed a predictable pattern of plagiocephaly (contralateral coronal sutures growing more than ipsilateral sutures and ipsilateral frontonasal and anterior lambdoidal sutures growing more than contralateral sutures), which resulted in early cranial vault deformities and a double "S" shape torquing towards the affected side. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent cytokine and genetic findings from human craniosynostotic studies. PMID:9694335

  6. Predicting occupancy for pygmy rabbits in Wyoming: an independent evaluation of two species distribution models

    USGS Publications Warehouse

    Germaine, Stephen; Ignizio, Drew; Keinath, Doug; Copeland, Holly

    2014-01-01

    Species distribution models are an important component of natural-resource conservation planning efforts. Independent, external evaluation of their accuracy is important before they are used in management contexts. We evaluated the classification accuracy of two species distribution models designed to predict the distribution of pygmy rabbit Brachylagus idahoensis habitat in southwestern Wyoming, USA. The Nature Conservancy model was deductive and based on published information and expert opinion, whereas the Wyoming Natural Diversity Database model was statistically derived using historical observation data. We randomly selected 187 evaluation survey points throughout southwestern Wyoming in areas predicted to be habitat and areas predicted to be nonhabitat for each model. The Nature Conservancy model correctly classified 39 of 77 (50.6%) unoccupied evaluation plots and 65 of 88 (73.9%) occupied plots for an overall classification success of 63.3%. The Wyoming Natural Diversity Database model correctly classified 53 of 95 (55.8%) unoccupied plots and 59 of 88 (67.0%) occupied plots for an overall classification success of 61.2%. Based on 95% asymptotic confidence intervals, classification success of the two models did not differ. The models jointly classified 10.8% of the area as habitat and 47.4% of the area as nonhabitat, but were discordant in classifying the remaining 41.9% of the area. To evaluate how anthropogenic development affected model predictive success, we surveyed 120 additional plots among three density levels of gas-field road networks. Classification success declined sharply for both models as road-density level increased beyond 5 km of roads per km-squared area. Both models were more effective at predicting habitat than nonhabitat in relatively undeveloped areas, and neither was effective at accounting for the effects of gas-energy-development road networks. Resource managers who wish to know the amount of pygmy rabbit habitat present in an

  7. Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

    PubMed

    Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

    2014-10-15

    Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used

  8. Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies.

    PubMed

    Sgouralis, Ioannis; Kett, Michelle M; Ow, Connie P C; Abdelkader, Amany; Layton, Anita T; Gardiner, Bruce S; Smith, David W; Lankadeva, Yugeesh R; Evans, Roger G

    2016-09-01

    Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2 Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2 Both intravenous infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin and infusion of N(G)-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8-17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r(2) = 0.87-0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2 Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1-0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10-50% of the change in pelvic urine/medullary Po2 Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

  9. Modeling of the Jack Rabbit Series of Experiments with a temperature-based reactive burn mode

    NASA Astrophysics Data System (ADS)

    Desbiens, Nicolas; Sorin, Remy; Dubois, Vincent

    2015-06-01

    A reactive burn model based on shocked explosive temperature has been presented at the previous joint AIRAPT/APS-SCCM in Seattle. It has been shown that the temperature of the unburnt shocked explosive is a good candidate to drive rate laws of decomposition. Such models are able to reproduce the evolution of the sensitivity of explosives with porosity. They also predict a drastic reduction of the reactivity in the case of multi-shock compression without any bolt-on desensitization model. In this work, we apply our temperature-based reactive burn model to the data of the Jack Rabbit Series of Experiments. Indeed, these experiments dedicated to the study of detonation wave corner turning and shock desensitization in LX-17 are harsh tests for reactive burn models. Details of our model together with preliminary results will be shown.

  10. Local and Remote Postconditioning Decrease Intestinal Injury in a Rabbit Ischemia/Reperfusion Model

    PubMed Central

    Yang, Mu; Dong, Jian-Xin; Li, Lu-Bin; Che, Hai-Jie; Yong, Jun; Song, Fu-Bo; Wang, Tao; Zhang, Jv-Wen

    2016-01-01

    Intestinal ischemia/reperfusion (I/R) injury is a significant problem that is associated with high morbidity and mortality in critical settings. This injury may be ameliorated using postconditioning protocol. In our study, we created a rabbit intestinal I/R injury model to analyze the effects of local ischemia postconditioning (LIPo) and remote ischemia postconditioning (RIPo) on intestinal I/R injury. We concluded that LIPo affords protection in intestinal I/R injury in a comparable fashion with RIPo by decreasing oxidative stress, neutrophil activation, and apoptosis. PMID:26819600

  11. Interceed and Estrogen Reduce Uterine Adhesions and Fibrosis and Improve Endometrial Receptivity in a Rabbit Model of Intrauterine Adhesions.

    PubMed

    Cai, Huihua; Li, Huijuan; He, Yuanli

    2016-09-01

    Intrauterine adhesions (IUA) remain a major cause of infertility. Interceed, a regenerated cellulose adhesion barrier, is used to prevent adhesions in abdominal cavity. This study aimed to determine whether Interceed could reduce adhesions and tissue fibrosis and improve endometrial receptivity (ER) in rabbit. Rabbits were randomized into 6 groups: sham operation, Interceed control, IUA model, Interceed therapy, estrogen therapy, and combination therapy. Four rabbits per group were euthanized to evaluate adhesion severity on the day before intervention and day 7, 14, and 28 after intervention. Number of endometrial glands and degree of endometrial fibrosis acted as markers for adhesion severity. Pseudopregnancy was induced in the remainder, and 8 rabbits per group were killed for assessing ER on days 6, 7, and 8 of pseudopregnancy by ανβ3 integrin and pinopode. We found that Interceed or estrogen therapy led to significant improvement in the adhesion severity on day 28 after intervention, respectively, compared to IUA model group (all P < .05). However, after combination therapy, such improvement achieved comparable to sham operation group as early as day 14 after intervention (glands, P = .711, fibrosis, P = .154). Among the IUA models treated, ER was highest after combination therapy on day 7 of pseudopregnancy, similar to sham operation group (integrin, P = .352, pinopode, P = .154). In conclusion, Interceed and estrogen reduce adhesions and tissue fibrosis and improve ER in a rabbit model and may be novel therapeutic approaches for infertility resulting from IUA. PMID:26895816

  12. The usefulness of optical analyses for detecting vulnerable plaques using rabbit models

    NASA Astrophysics Data System (ADS)

    Nakai, Kanji; Ishihara, Miya; Kawauchi, Satoko; Shiomi, Masashi; Kikuchi, Makoto; Kaji, Tatsumi

    2011-03-01

    Purpose: Carotid artery stenting (CAS) has become a widely used option for treatment of carotid stenosis. Although technical improvements have led to a decrease in complications related to CAS, distal embolism continues to be a problem. The purpose of this research was to investigate the usefulness of optical methods (Time-Resolved Laser- Induced Fluorescence Spectroscopy [TR-LIFS] and reflection spectroscopy [RS] as diagnostic tools for assessment of vulnerable atherosclerotic lesions, using rabbit models of vulnerable plaque. Materials & Methods: Male Japanese white rabbits were divided into a high cholesterol diet group and a normal diet group. In addition, we used a Watanabe heritable hyperlipidemic (WHHL) rabbit, because we confirmed the reliability of our animal model for this study. Experiment 1: TR-LIFS. Fluorescence was induced using the third harmonic wave of a Q switch Nd:YAG laser. The TR-LIFS was performed using a photonic multi-channel analyzer with ICCD (wavelength range, 200 - 860 nm). Experiment 2: RS. Refection spectra in the wavelength range of 900 to 1700 nm were acquired using a spectrometer. Results: In the TR-LIFS, the wavelength at the peak was longer by plaque formation. The TR-LIFS method revealed a difference in peak levels between a normal aorta and a lipid-rich aorta. The RS method showed increased absorption from 1450 to 1500 nm for lipid-rich plaques. We observed absorption around 1200 nm due to lipid only in the WHHL group. Conclusion: These methods using optical analysis might be useful for diagnosis of vulnerable plaques. Keywords: Carotid artery stenting, vulnerable plaque, Time-Resolved Laser-Induced Fluorescence

  13. Echistatin prevents posterior capsule opacification in diabetic rabbit model via integrin linked kinase signaling pathway

    PubMed Central

    Lin, Fengbin; Chen, Yingying; Liang, Hao; Tan, Shaojian

    2015-01-01

    Purpose: To investigate the effect of disintegrin echistatin on integrin linked kinase (ILK) and subsequent PI3-K/Akt and ERK1/2 signaling pathways in the posterior capsule opacification (PCO) model of diabetic rabbit. Methods: 56 rabbits were injected alloxan to model diabetic. Then they accepted lens extraction surgery and randomly and intraoperatively injected distilled water (control group; n = 28) or 10.0 mg·L-1 echistatin (echistatin-treated group; n = 28) into the anterior chamber. Each group was subdivided into ten days group (n = 14) and six weeks group (n = 14) respectively. The PCO severity was evaluated with a slit lamp microscope and light microscope for 10 days and 6 weeks postoperatively. The levels of ILK in the posterior capsule were determined by Q-PCR, Western blotting and Immunohistochemistry. Akt and ERK1/2 phosphorylation were analyzed by Western blotting. Results: 10 days and 6 weeks after surgery, the grades of PCO in the echistatin-treated group were lower than the control group. The lens epithelial cells (LECs) in the posterior capsule of echistatin-treated eyes had decreased degrees of proliferation and migration than the control group. And no significant side effects appeared after treated with echistatin. Echistatin could significantly reduce the expression of ILK in terms of both mRNA and protein levels. The phosphorylation levels of Akt and ERK1/2 were decreased in the echistatin-treated group compared with the control group. Conclusions: Echistatin could inhibit postoperative PCO occurrence and development in diabetic rabbit eyes, which may be related to down-regulation the expression of ILK and inhibition the PI3-K/Akt and ERK1/2 pathways. PMID:26823745

  14. Effects of berberine on β-secretase activity in a rabbit model of Alzheimer's disease

    PubMed Central

    Panahi, Negar; Mahmoudian, Massoud; Mortazavi, Pejman

    2013-01-01

    Introduction Relevant aspects of Alzheimer's disease (AD) can be modeled by aluminium-maltolate injection into specific regions of the brain. The possible role of berberine chloride (BC) as an anti-inflammatory agent in the brain has been previously addressed. Material and methods Rabbits were divided into control (C), untreated lesion (L) and BC-treated + lesion (L + BC) groups. Animals in L + BC received BC (50 mg/ kg) orally 1 day after surgery and daily for 2 weeks. The lesion was induced by injection of 100 µl of either vehicle or water containing 25 mM aluminium-maltol into intraventricular fissure. Weight loss, ataxia, paralysis and tremor were monitored. For histopathology, Bielschowsky silver and H&E staining were employed. β-Secretase activity in hippocampus was finally assessed. Results All L animals died on days 12-15 after lesion. Seven to 10 days after lesion, abnormal symptoms as well as cachexia were seen in over 90% of cases. L rabbits lost an average of 0.5 kg which was significant on days 10 and 12 (p < 0.05); this was not completely prevented by BC. Up to day 15, all L animals had lost their lives (p < 0.001). BC treatment protected the hippocampus from degeneration, altered the behavior and decreased the activity of β-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Conclusions Considering the findings in regard to physiological abilities, histological changes and BACE-1 activity in hippocampus changes, it is concluded that BC treatment could be an effective therapy in restoring Al maltol-induced behavioral derangements in the rabbit model of AD. PMID:23516061

  15. Assessment of SiCaP-30 in a Rabbit Posterolateral Fusion Model with Concurrent Chemotherapy.

    PubMed

    Smucker, Joseph D; Petersen, Emily B; Al-Hili, Ali; Nepola, James V; Fredericks, Douglas C

    2015-01-01

    Chemotherapy derivatives of the rabbit posterolateral fusion model are considered a challenging environment in which to test bone graft materials. The purpose of this study was to determine the performance characteristics of SiCaP-30 as a bone graft substitute relative to autograft (iliac crest bone graft [ICBG]), Actifuse ABX and β-Tricalcium Phosphate-Bioactive Glass-Type I Collagen (βTCP-BG) in a rabbit posterolateral spine fusion model with concurrent chemotherapy treatment This was a randomized, controlled study in a laboratory setting with blinded assessment of fusion by manual palpation and flexibility testing. Sixty rabbits were entered into the study with 45 used for analysis. Chemotherapeutic agents, doxorubicin and cis-platin (2.5 mg/kg), were administered one week prior to surgery, and one, two and three weeks post surgery. Bilateral posterolateral lumbar intertransverse process fusions were performed at L5-L6. The lateral two thirds of the transverse processes were decorticated and covered with 3cc/side of one of the following graft materials: autologous ICBG, Actifuse ABX (ApaTech Ltd, UK), Vitoss BA (Orthovita, USA) or SiCaP-30 (ApaTech Ltd., UK). Animals were euthanized 12 weeks post surgery. The ICBG group had a 45% (5/11) manual palpation fusion rate and correlated with motion analysis fusion results of 36% (4/11). The Actifuse ABX group had a 33% (4/12) manual palpation fusion rate and a motion analysis fusion rate of 25% (3/12). No motion segments in the Vitoss BA group (0/11) showed any signs of fusion. The SiCaP-30 group demonstrated a statistically higher manual palpation and motion analysis fusion rate of 82% (9/11; p<0.05) and produced superior bone formation compared with Actifuse ABX and βTCP-BG. PMID:26361457

  16. Voxel modeling of rabbits for use in radiological dose rate calculations.

    PubMed

    Caffrey, E A; Johansen, M P; Higley, K A

    2016-01-01

    Radiation dose to biota is generally calculated using Monte Carlo simulations of whole body ellipsoids with homogeneously distributed radioactivity throughout. More complex anatomical phantoms, termed voxel phantoms, have been developed to test the validity of these simplistic geometric models. In most voxel models created to date, human tissue composition and density values have been used in lieu of biologically accurate values for non-human biota. This has raised questions regarding variable tissue composition and density effects on the fraction of radioactive emission energy absorbed within tissues (e.g. the absorbed fraction - AF), along with implications for age-dependent dose rates as organisms mature. The results of this study on rabbits indicates that the variation in composition between two mammalian tissue types (e.g. human vs rabbit bones) made little difference in self-AF (SAF) values (within 5% over most energy ranges). However, variable tissue density (e.g. bone vs liver) can significantly impact SAF values. An examination of differences across life-stages revealed increasing SAF with testis and ovary size of over an order of magnitude for photons and several factors for electrons, indicating the potential for increasing dose rates to these sensitive organs as animals mature. AFs for electron energies of 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, 2.0, and 4.0 MeV and photon energies of 0.01, 0.015, 0.02, 0.03, 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0, and 4.0 MeV are provided for eleven rabbit tissues. The data presented in this study can be used to calculate accurate organ dose rates for rabbits and other small rodents; to aide in extending dose results among different mammal species; and to validate the use of ellipsoidal models for regulatory purposes. PMID:25971772

  17. Characterization of early changes in fetoplacental hemodynamics in a diet-induced rabbit model of IUGR.

    PubMed

    López-Tello, J; Barbero, A; González-Bulnes, A; Astiz, S; Rodríguez, M; Formoso-Rafferty, N; Arias-Álvarez, M; Rebollar, P G

    2015-10-01

    Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research. PMID:26268616

  18. A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

    PubMed Central

    El Backly, Rania M.; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX®) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12–16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX®) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute. PMID:25610828

  19. Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment.

    PubMed

    Bimonte, Sabrina; Leongito, Maddalena; Piccirillo, Mauro; de Angelis, Cristina; Pivonello, Claudia; Granata, Vincenza; Izzo, Francesco

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models. PMID:27525037

  20. A modified rabbit ulna defect model for evaluating periosteal substitutes in bone engineering: a pilot study.

    PubMed

    El Backly, Rania M; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX(®)) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12-16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX(®)) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute. PMID:25610828

  1. Role of Endolysosomes in Skeletal Muscle Pathology Observed in a Cholesterol-Fed Rabbit Model of Alzheimer’s Disease

    PubMed Central

    Chen, Xuesong; Wagener, John F.; Ghribi, Othman; Geiger, Jonathan D.

    2016-01-01

    Deficits in skeletal muscles contribute not only to the functional decline in people living with Alzheimer’s disease (AD), but also to AD pathogenesis. We have shown that endolysosome dysfunction plays an important role in the development of AD pathological features in a cholesterol-fed rabbit model of AD. Interestingly we observed in skeletal muscle from the rabbit AD model increased deposition of Aβ, phosphorylated tau, and ubiquitin. Here, we tested the hypothesis that endolysosome dysfunction commonly occurs in skeletal muscle and brain in this rabbit model of AD. In skeletal muscle of rabbits fed a 2% cholesterol-enriched diet for 12 weeks we observed the presence of abnormally enlarged endolysosomes, in which were increased accumulations of free cholesterol and multiple AD marker proteins subject to misfolding and aggregation including Aβ, phosphorylated tau, and ubiquitin. Moreover, in skeletal muscle of rabbits fed the cholesterol-enriched diet we observed decreased specific activities of three different lysosome enzymes. Our results suggest that elevated levels of plasma cholesterol can disturb endolysosome structure and function as well as promote the development of AD-like pathological features in skeletal muscle and that these organellar changes might contribute to the development of skeletal muscle deficits in AD. PMID:27375475

  2. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model.

    PubMed

    Nag, Dhrubajyoti; Sinha, Ritam; Mitra, Soma; Barman, Soumik; Takeda, Yoshifumi; Shinoda, Sumio; Chakrabarti, M K; Koley, Hemanta

    2015-11-01

    Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing rabbits with a reduced number of oral doses and evaluating the host's adaptive immune responses. The duration of immunogenicity and subsequently protective efficacy was determined against wild type heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains were detected by immunoblot assay. Up-regulation of IL-12p35, IFN-γ and IL-10 mRNA expression was detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided complete protection in a rabbit model. These immunogens could be a broad spectrum non-living vaccine candidate for human use in the near future. PMID:26210044

  3. Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

    PubMed Central

    LIU, JIAYI; LI, NING; LI, LI; LI, DANYE; LIU, KAI; ZHAO, LINGYUN; TANG, JINTIAN; LI, LIYA

    2013-01-01

    Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment. PMID:24260045

  4. Sclera-Choroid-RPE Transport of Eight β-Blockers in Human, Bovine, Porcine, Rabbit, and Rat Models

    PubMed Central

    Kadam, Rajendra S.; Cheruvu, Narayan P. S.; Edelhauser, Henry F.

    2011-01-01

    Purpose. To determine the influence of drug lipophilicity, ocular pigmentation, and species differences on transscleral solute transport. Methods. The transport of eight β-blockers across excised sclera/sclera-choroid-RPE (SCRPE) of albino rabbit, pigmented rabbit, human, porcine, and bovine eyes was determined over 6 hours. The ex vivo transscleral β-blocker transport to the vitreous at the end of 6 hours was determined in euthanatized, pigmented Brown Norway rats. The thicknesses of the sclera and SCRPE and the melanin content in choroid-RPE (CRPE) were measured to determine whether species differences in drug transport can be explained on this basis. Results. Solute lipophilicity inversely correlated with the SCRPE cumulative percentage of transport in all species (R2 ≥ 0.80). The CRPE impeded the SCRPE transport of all β-blockers (51%–64% resistance in the rabbits; 84%–99.8% in the bovine and porcine eyes) more than the sclera, with the impedance increasing with lipophilicity. SCRPE transport followed the trend albino rabbit > pigmented rabbit > human > porcine > bovine, and a cross-species comparison showed good Spearman's rho correlation (R2 ≥ 0.85). Bovine (R2 = 0.84), porcine (R2 = 0.84), and human (R2 = 0.71) SCRPE transport was more predictive than that in the rabbit models (R2 = 0.60–0.61) of transscleral solute transport to the vitreous in rats. The CRPE concentrations were higher in pigmented rabbits than in albino rabbits. The melanin content of the CRPE exhibited the trend albino rabbit ≪ pigmented rabbit < porcine ∼ bovine < rat. Normalization to scleral thickness abolished the species differences in scleral transport. Normalization to SCRPE thickness and melanin content significantly reduced species differences in SCRPE transport. Conclusions. Owing to the presence of pigment and drug binding, choroid-RPE is the principal barrier to transscleral β-blocker transport, with the barrier being more significant for lipophilic

  5. Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

    NASA Astrophysics Data System (ADS)

    Umetani, Keiji; Uesugi, Kentaro; Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki

    2009-10-01

    Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 μm has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results

  6. Odanacatib increases mineralized callus during fracture healing in a rabbit ulnar osteotomy model.

    PubMed

    Pennypacker, Brenda L; Gilberto, David; Gatto, Nicholas T; Samadfam, Rana; Smith, Susan Y; Kimmel, Donald B; Duong, Le Thi

    2016-01-01

    The effects of the cathepsin K inhibitor odanacatib (ODN) on fracture healing were monitored for ~6 and 15 weeks post-fracture in two separate studies using the unilateral transverse mid-ulnar osteotomy model in skeletally mature female rabbits. Rabbits were pre-treated for 3-4 weeks with vehicle (Veh), ODN (2 mg/kg, po, daily), or alendronate (ALN) (0.3 mg/kg, sc, twice-weekly) prior to osteotomy. In Study 1, the animals were maintained on the same respective treatment for ~6 weeks. In Study 2, the animals were also continued on the same therapy or switched from Veh to ODN or ODN to Veh for 15 weeks. No treatment-related impairment of fracture union was seen by qualitative histological assessments in the first study. Cartilage retention was detected in the calluses of ALN-treated rabbits at week-6, while calluses in the ODN and Veh groups contained bony tissue with significantly less residual cartilage. ODN treatment also markedly increased the number of cathepsin K-(+) osteoclasts in the callus, indicating enhanced callus remodeling. From the second study, ex vivo DXA and pQCT confirmed that ODN treatment pre- and post-osteotomy increased callus bone mineral content and bone mineral density (BMD) versus Veh (p < 0.001) and discontinuation of ODN post-surgery returned callus BMD to Veh. Peak load of ODN- or ALN-treated calluses were comparable to Veh. ODN increased callus yield load (20%, p = 0.056) and stiffness (26%, p < 0.05) versus Veh. These studies demonstrated that ODN increased mineralized callus during the early phase of fracture repair without impairing callus formation or biomechanical integrity at the fracture site. PMID:26178170

  7. Newly designed “pieced” stent in a rabbit model of benign esophageal stricture

    PubMed Central

    Liu, Jin; Shang, Liang; Liu, Ji-Yong; Qin, Cheng-Yong

    2015-01-01

    AIM: To investigate a newly designed stent and its dilatation effect in a rabbit model of benign esophageal stricture. METHODS: Thirty-four New Zealand white rabbits underwent a corrosive injury in the middle esophagus for esophageal stricture formation. Thirty rabbits with a successful formation of esophageal strictures were randomly allocated into two groups. The control group (n = 15) was implanted with a conventional stent, and the study group (n = 15) was implanted with a detachable “pieced” stent. The study stent (30 mm in length, 10 mm in diameter) was composed of three covered metallic pieces connected by surgical suture lines. The stent was collapsed by pulling the suture lines out of the mesh. Two weeks after stricture formation, endoscopic placement of a conventional stent or the new stent was performed. Endoscopic extraction was carried out four weeks later. The extraction rate, ease of extraction, migration, complications, and survival were evaluated. RESULTS: Stent migration occurred in 3/15 (20%) animals in the control group and 2/15 (13%) animals in the study group; the difference between the two groups was not statistically significant. At the end of four weeks, the remaining stents were successfully extracted with the endoscope in 100% (11/11) of the animals in the study group, and 60% (6/10) of the animals in the control group; this difference was statistically significant (P < 0.05). There was no difference in the mean number of follow-up days between the control and study groups (25.33 vs 25.85). Minor bleeding was reported in five cases in the study group and four in the control group. There were no severe complications directly associated with stent implantation or extraction in either of the two groups. CONCLUSION: In this experimental protocol of benign esophageal strictures, the novel “pieced” stent demonstrated a superior removal rate with a similar migration rate compared to a conventional stent. PMID:26229404

  8. Enhanced in vivo delivery of 5-fluorouracil by ethosomal gels in rabbit ear hypertrophic scar model.

    PubMed

    Wo, Yan; Zhang, Zheng; Zhang, Yixin; Zhang, Zhen; Wang, Kan; Mao, Xiaohui; Su, Weijie; Li, Ke; Cui, Daxiang; Chen, Jun

    2014-01-01

    Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs) was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI) of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future. PMID:25501333

  9. Oxidative Stress and Histological Changes in a Model of Retinal Phototoxicity in Rabbits

    PubMed Central

    Heras-Mulero, Henar; Fernández-Robredo, Patricia; Recalde, Sergio; Hernández, María; Reiter, Nicholas; Moreno-Orduña, Maite; García-Layana, Alfredo

    2014-01-01

    Photochemical damage occurs after an exposure to high energy radiation within the visible spectrum of light, causing morphological changes in the retina and the formation of superoxide anion. In this study we created a model of phototoxicity in rabbits. Animals were exposed to a light source for 120 minutes and were sacrificed immediately or one week after exposure. Outer nuclear layer and neurosensory retina thickness measurements and photoreceptor counting were performed. Caspase-1 and caspase-3 were assessed by immunohistochemistry. Dihydroethidium was used to evaluate in situ generation of superoxide and thiobarbituric acid reactive substances were measured in retinal homogenates as indicators of lipid peroxidation. The total antioxidant capacity and oxidative ratio were also determined. Retinas from rabbits exposed to light showed higher levels of lipid peroxidation than the unexposed animals and a decrease in outer nuclear layer and neurosensory retina thickness. Our study demonstrates that light damage produces an increase in retinal oxidative stress immediately after light exposure that decreases one week after exposure. However, some morphological alterations appear days after light exposure including apoptotic phenomena. This model may be useful in the future to study the protective effect of antioxidant substances or new intraocular lenses with yellow filters. PMID:24991304

  10. The Streptococcus sanguinis Competence Regulon Is Not Required for Infective Endocarditis Virulence in a Rabbit Model

    PubMed Central

    Callahan, Jill E.; Munro, Cindy L.; Kitten, Todd

    2011-01-01

    Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species. PMID:22039480

  11. Early osseointegration of a strontium containing glass ceramic in a rabbit model.

    PubMed

    Sabareeswaran, Arumugan; Basu, Bikramjit; Shenoy, Sachin J; Jaffer, Zahira; Saha, Naresh; Stamboulis, Artemis

    2013-12-01

    The most important property of a bone cement or a bone substitute in load bearing orthopaedic implants is good integration with host bone with reduced bone resorption and increased bone regeneration at the implant interface. Long term implantation of metal-based joint replacements often results in corrosion and particle release, initiating chronic inflammation leading onto osteoporosis of host bone. An alternative solution is the coating of metal implants with hydroxyapatite (HA) or bioglass or the use of bulk bioglass or HA-based composites. In the above perspective, the present study reports the in vivo biocompatibility and bone healing of the strontium (Sr)-stabilized bulk glass ceramics with the nominal composition of 4.5SiO2-3Al2O3-1.5P2O5-3SrO-2SrF2 during short term implantation of up to 12 weeks in rabbit animal model. The progression of healing and bone regeneration was qualitatively and quantitatively assessed using fluorescence microscopy, histological analysis and micro-computed tomography. The overall assessment of the present study establishes that the investigated glass ceramic is biocompatible in vivo with regards to local effects after short term implantation in rabbit animal model. Excellent healing was observed, which is comparable to that seen in response to a commercially available implant of HA-based bioglass alone. PMID:24050873

  12. Enhanced in Vivo Delivery of 5-Fluorouracil by Ethosomal Gels in Rabbit Ear Hypertrophic Scar Model

    PubMed Central

    Wo, Yan; Zhang, Zheng; Zhang, Yixin; Zhang, Zhen; Wang, Kan; Mao, Xiaohui; Su, Weijie; Li, Ke; Cui, Daxiang; Chen, Jun

    2014-01-01

    Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs) was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI) of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future. PMID:25501333

  13. The role of myofibroblasts in the development of osteoradionecrosis in a newly established rabbit model.

    PubMed

    Zong, Chunlin; Cai, Bolei; Wen, Xinxin; Alam, Syed; Chen, Yuanli; Guo, Yuxuan; Liu, Yanpu; Tian, Lei

    2016-06-01

    This study aimed to establish a proper animal model of osteoradionecrosis of jaws (ORNJ) and to observe preliminarily the characteristics of myofibroblasts, the key effector cell of fibrosis, in ORNJ. Rabbit mandibles were irradiated at three different doses based on a human equivalent radiation schedule, and examined by gross manifestation, single-photon emission computed tomography (SPECT), micro-computed tomography, sequential fluorochrome labeling, and histology. Immunohistochemistry staining of α-SMA was applied to detect the existence of myofibroblasts. The exposed necrotic bone, which is the main indication of ORNJ, started to be observed at all rabbits at 9 Gy. With the radiation dose increasing, the microarchitecture of the irradiated mandibles was more destroyed, the metabolism and mineralization of the irradiated mandibles diminished, the osteocytes number decreased, and more mature bones were substituted by fibrosis in the irradiated mandibles. In addition, as the radiation dose increased, the myofibroblast number increased and collected around the separated sequestrum, which indicated that myofibroblasts might relate to the pathogenesis of ORNJ. In summary, a clinically translational ORNJ model was successfully established in our study, and the role of myofibroblasts in the pathogenesis of ORNJ is described for the first time. PMID:27150352

  14. Electrophysiology of Heart Failure Using a Rabbit Model: From the Failing Myocyte to Ventricular Fibrillation

    PubMed Central

    Liu, Michael; Qu, Zhilin; Weiss, James N.; Ennis, Daniel B.; Klug, William S.; Garfinkel, Alan

    2016-01-01

    Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we compared the electrical wave propagation in one dimensional cables of healthy and failing cells. The validated cell model was then used to simulate the EP of heart failure in an anatomically accurate biventricular rabbit model. As pacing cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing. Moreover, T-wave alternans is significantly more pronounced in the failing heart. At rapid pacing, APD maps show areas of conduction block in the failing heart. Finally, accelerated pacing initiated wave reentry and breakup in the failing heart. Further, the onset of VF was not observed with an upregulation of SERCA, a potential drug therapy, using the same protocol. The changes introduced at the cell and tissue level have increased the failing heart’s susceptibility to dynamic instabilities and arrhythmias under rapid pacing. However, the observed increase in arrhythmogenic potential is

  15. Electrophysiology of Heart Failure Using a Rabbit Model: From the Failing Myocyte to Ventricular Fibrillation.

    PubMed

    Ponnaluri, Aditya V S; Perotti, Luigi E; Liu, Michael; Qu, Zhilin; Weiss, James N; Ennis, Daniel B; Klug, William S; Garfinkel, Alan

    2016-06-01

    Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we compared the electrical wave propagation in one dimensional cables of healthy and failing cells. The validated cell model was then used to simulate the EP of heart failure in an anatomically accurate biventricular rabbit model. As pacing cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing. Moreover, T-wave alternans is significantly more pronounced in the failing heart. At rapid pacing, APD maps show areas of conduction block in the failing heart. Finally, accelerated pacing initiated wave reentry and breakup in the failing heart. Further, the onset of VF was not observed with an upregulation of SERCA, a potential drug therapy, using the same protocol. The changes introduced at the cell and tissue level have increased the failing heart's susceptibility to dynamic instabilities and arrhythmias under rapid pacing. However, the observed increase in arrhythmogenic potential is

  16. Electrocardiograms corresponding to the development of myocardial infarction in anesthetized WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia.

    PubMed

    Kobayashi, Tsutomu; Ito, Takashi; Yamada, Satoshi; Kuniyoshi, Nobue; Shiomi, Masashi

    2012-10-01

    The aim of this study was to determine whether features indicative of myocardial ischemia occur in the electrocardiograms (ECG) in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for human familial hypercholesterolemia. ECG were recorded in 110 anesthetized WHHLMI rabbits (age, 10 to 39 mo) by using unipolar and bipolar limb leads with or without chest leads. We noted the following electrocardiographic changes: T wave inversion (37.4%), ST segment depression (31.8%), deep Q wave (16.3%), reduced R wave amplitude (7.3%), ST segment elevation (2.7%), and high T wave (1.8%). These ECG changes resembled those in human patients with coronary heart disease. Histopathologic examination revealed that the left ventricular wall showed acute myocardial lesions, including loss of cross-striations, vacuolar degeneration, coagulation necrosis of cardiac myocytes, and edema between myofibrils, in addition to chronic myocardial lesions such as myocardial fibrosis. The coronary arteries that caused these ECG changes were severely stenosed due to atherosclerotic lesions. Ischemic ECG changes corresponded to the locations of the myocardial lesions. Normal ECG waveforms were similar between WHHLMI rabbits and humans, in contrast to the large differences between rabbits and mice or rats. In conclusion, ischemic ECG changes in WHHLMI rabbits reflect the location of myocardial lesions, making this model useful for studying coronary heart disease. PMID:23114045

  17. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  18. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  19. A rabbit model for mucosal immunity in the bowel. II. Local cellular reactivity to virus infection.

    PubMed Central

    Ramsay, A J; Holmes, M J

    1990-01-01

    An animal model was used to examine local and systemic cellular reactivity against virus infection of bowel mucosa. Firstly, existing techniques for extracting lymphoid cells from the dispersed populations of the bowel mucosa were adapted for use in rabbits and viable lymphocytes were isolated from the lapine ileal mucosa in numbers suitable for assay. Lamina propria lymphocytes (LPL) showed a strong blastogenic response to T-cell mitogens but intra-epithelial lymphocytes (IEL) responded poorly, even in the presence of splenic accessory cells. Next, chronically isolated ileal loops in rabbits were infected with parainfluenzavirus type 3 (PI-3) and isolates from the organized and dispersed lymphoid tissues associated with infected ileal mucosae and those from systemic lymphoid sites were used in in vitro assays of virus-specific lympho-proliferation. A T-cell-mediated immune response against PI-3 was mounted in lymphoid tissues associated with the infected loops, appearing first in loop Peyer's patches (PP) at Day 4 and in mesenteric lymph nodes (MLN) and lamina propriae at Day 7 after infection. The response in PP had waned by 21 days but was sustained in the other sites for at least 42 days. Epithelial lymphocytes were consistently anergic and there was no evidence of specific reactivity at systemic lymphoid sites or elsewhere in the bowel. Thus, a highly localized T-cell-mediated response was sustained, not only in organized lymphoid tissues but also in the bowel wall itself, following infection with a novel antigen. PMID:2155872

  20. Trypanosoma evansi: A clinical, parasitological and immunological evaluation of trypanosomosis using a chronic rabbit model

    PubMed Central

    Ramírez-Iglesias, J.R.; Eleizalde, M.C.; Gómez-Piñeres, E.; Mendoza, M.

    2012-01-01

    We evaluated the clinical, parasitological and immunological effects of a Venezuelan strain of Trypanosoma evansi (T. evansi) throughout in experimentally inoculated rabbits over the course of infection and compared them with the same aspect in healthy animals. Body temperature was recorded in degrees Celsius, animal weight in kilograms, serum proteins in g/dl using a refractometer, haematocrit percentage by capillary centrifugation and the anti-T. evansi IgG titer by indirect ELISA immunoassay, from both infected animals and controls for 95 days. Infected animals showed a higher body temperature, total serum protein and anti- T. evansi antibody titer, and a lower haematocrit and weight gain than controls. These differences were related to the presence of the parasites in the blood as detected micro-haematocrit centrifugation technique (MHCT) and direct microscopic examination (DME). This study confirms the usefulness of rabbits as a model for the study of trypanosomosis; the clinical features of the disease can be observed and the three characteristic stages, prepatent period, acute and chronic phase clearly defined over the course of the infection. PMID:26623297

  1. (18)F-FLT PET/CT imaging in a Wister rabbit inflammation model.

    PubMed

    Tan, Yeying; Liang, Jun; Liu, Defeng; Zhu, Feng; Wang, Guanmin; Ding, Xuemei; Han, Conghui

    2014-07-01

    The aim of the present study was to determine the tumour specificity of the newly developed nucleoside metabolic positron emission tomography (PET) tracer, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT). Using (18)F-FLT PET imaging, DNA synthesis and cell proliferation were detected in Staphylococcus aureus (S. aureus) abscess and calcium sulphate models in Wister rabbits. A total of eight rabbits were implanted with S. aureus in the left tibia to induce an inflammatory process. Calcium sulphate + gentamicin was implanted in the right tibia to induce a physical stimulus without bacterial multiplication. After four weeks, the animals underwent (18)F-FLT PET imaging, bacterial culturing and tissue pathology. The uptake of (18)F-FLT was significantly higher in the abscess site compared with that in the granuloma, with maximum standardised uptake values of 5.76±0.25 and 1.15±0.32, respectively (P<0.01). This indicates that (18)F-FLT is not a specific tumour tracer since active inflammation also results in the uptake of this compound. However, the tumour specificity of this tracer is higher compared with that of (18)F-fluorodeoxyglucose. Therefore, (18)F-FLT may be useful in the differential diagnosis of benign and malignant tumours. PMID:24944599

  2. Acute exposure to hair bleach causes airway hyperresponsiveness in a rabbit model.

    PubMed

    Mensing, T; Marek, W; Raulf-Heimsoth, M; Baur, X

    1998-12-01

    Ammonium persulphate (APS) and hydrogen peroxide (H2O2) are used as oxidants in many industrial processes and are the main constituents of standard hair bleaching products. In a previous study, it was demonstrated that aerosols of APS induce alterations in airway responsiveness. The present study examined whether exposure for 4 h to a hair bleach composition (containing APS, potassium persulphate and H2O2) or H2O2 could induce airway hyperresponsiveness and/or an obstructive ventilation pattern in a rabbit model. Exposure to the aerosols altered neither baseline airway resistance, dynamic elastance, slope of inspiratory pressure generation nor arterial blood pressure and blood gas measurements. Similarly to APS, hair bleach aerosols containing > or =10.9 mg x m(-3) persulphate (ammonium and potassium salt) in air and > or =1.36 mg x m(-3) H2O2 in air caused airway hyperresponsiveness to acetylcholine after 4 h of exposure. Aerosolized H2O2 (> or =37 mg x m(-3) in air) did not influence airway responsiveness to acetylcholine. The results demonstrate that hair bleaching products containing persulphates dissolved in H2O2 cause airway hyperresponsiveness to acetylcholine in rabbits. PMID:9877493

  3. Histological evaluation of condylar hyperplasia model of rabbit following distraction osteogenesis of the condylar neck.

    PubMed

    Meng, Q; Chen, G; Long, X; Deng, M; Cai, H; Li, J

    2011-01-01

    Condylar hyperplasia is the excessive unilateral growth of mandibular leading to facial asymmetry, occlusal disturbance, joint pain and dysfunction. The aim of this study is to evaluate the histological presence of temporomandibular joint in model of condylar hyperplasia by lengthening unilateral condylar neck of distraction osteogenesis. An extra oral distractor was employed to achieve unilateral condylar neck distraction (1·0 mm daily for 7 days). The experimental condylar necks were elongated by 7 mm compared to the contralateral. Eleven adult white rabbits were used. Eight rabbits were, respectively, sacrificed after the post-distraction period (4 or 8 weeks). All animals were evaluated clinically and histomorphometrically. The condyles radiologically showed remodelling, flattening and sclerosis. In 4-week group, thinning of the cartilage was evident, and the trabeculae were long, not multiply connected. A thin, dense fibrous layer covered all over the surface of cartilage. In 8-week group, the cartilaginous layer was similar to thickness of the normal cartilage, but still thinner than control. However, the fibrous layers covering condyle manifested slight degenerative changes, and even depressions and erosions were seen in the cartilage and subchondral bone. The trabeculae showed denser and multiply connected. In 8-week group, the cartilaginous thickness of surgical condyles was significantly thinner than the contralateral. This study indicates that unilateral distraction of condylar neck loads the condyles asymmetrically. Asymmetrical loads affect more on the surgical condyles than the contralateral, and after 8 weeks of the post-distraction, condyle could recover from asymmetrical loads in some degree. PMID:20626572

  4. Second harmonic generation imaging of skin wound healing and scarring in a rabbit ear model

    NASA Astrophysics Data System (ADS)

    Tang, Yiyan; Zhu, Xiaoqin; Xiong, Shuyuan; Chen, Jianxin

    2012-12-01

    Skin wound healing and scarring in rabbit ears was examined by second harmonic generation (SHG) microscopy. Rabbit ear wound model was created by punching from the ventral surface with removal of epidermis, dermis and perichondrium. The samples were collected weekly, and cut into 100 μm thickness sections for SHG imaging. SHG imaging system was operated at 810 nm, producing SHG signals at half the excitation wavelength 405 nm. A Plan-Neofluar objective (x40 and NA=0.75) was employed for focusing the excitation beam into tissue samples and was also used to collect the backscattered intrinsic SHG signals. Our results showed apparent difference in collagen content and microstructure at various wound healing and scarring time points. It suggested that SHG signals from collagen can serve as a good indicator for characterization of wound status. With the advancement on miniaturization, microscopy based on SHG will become a valuable tool for monitoring the wound healing and scarring in vivo, and help to guide the improvement of scar appearance with appropriate and subtle modulation during wound healing based on better understanding of scarring response mechanism.

  5. A cornea substitute derived from fish scale: 6-month followup on rabbit model.

    PubMed

    Yuan, Fei; Wang, Liyan; Lin, Chien-Chen; Chou, Cheng-Hung; Li, Lei

    2014-01-01

    A fish scale-derived cornea substitute (Biocornea) is proposed as an alternative for human donor corneal tissue. We adopt a regenerative medicine approach to design a primary alternative to the use of fish scale for restoring sight by corneal replacement. Biocornea with corneal multilayer arrangement collagen was implanted to rabbits by pocket implantation. Our study demonstrated the safety and detailed morphologic and physiologic results from the 6 months of followup of rabbit model. In the peripheral Biocornea, the collagen fibrils were arranged in reticular fashion. Slit lamp examination showed that haze and an ulcer were not observed in all groups at 3 months postoperatively while all corneas with Biocornea were clear at both 3 months and 6 months postoperatively. The interface of Biocornea and stromal tissue were filled successfully and without observable immune cells at postoperative day 180. Moreover, the Biocornea was not dissolved and degenerated but remained transparent and showed no apparent fragmentation. Our study demonstrated that the Biocornea derived from fish scale as a good substitute had high biocompatibility and support function after a long-term evaluation. This revealed that the new approach of using Biocornea may yield an ideal artificial cornea substitute for long-term inlay placement. PMID:25089206

  6. A Cornea Substitute Derived from Fish Scale: 6-Month Followup on Rabbit Model

    PubMed Central

    Yuan, Fei; Wang, Liyan; Lin, Chien-Chen; Chou, Cheng-Hung; Li, Lei

    2014-01-01

    A fish scale-derived cornea substitute (Biocornea) is proposed as an alternative for human donor corneal tissue. We adopt a regenerative medicine approach to design a primary alternative to the use of fish scale for restoring sight by corneal replacement. Biocornea with corneal multilayer arrangement collagen was implanted to rabbits by pocket implantation. Our study demonstrated the safety and detailed morphologic and physiologic results from the 6 months of followup of rabbit model. In the peripheral Biocornea, the collagen fibrils were arranged in reticular fashion. Slit lamp examination showed that haze and an ulcer were not observed in all groups at 3 months postoperatively while all corneas with Biocornea were clear at both 3 months and 6 months postoperatively. The interface of Biocornea and stromal tissue were filled successfully and without observable immune cells at postoperative day 180. Moreover, the Biocornea was not dissolved and degenerated but remained transparent and showed no apparent fragmentation. Our study demonstrated that the Biocornea derived from fish scale as a good substitute had high biocompatibility and support function after a long-term evaluation. This revealed that the new approach of using Biocornea may yield an ideal artificial cornea substitute for long-term inlay placement. PMID:25089206

  7. Human Umbilical Cord Blood Cells Ameliorates Motor Deficits In Rabbits In a Cerebral Palsy Model

    PubMed Central

    Drobyshevsky, A.; Cotten, C. M.; Shi, Z.; Luo, K.; Jiang, R.; Derrick, M.; Tracy, E. T.; Gentry, T.; Goldberg, R. N.; Kurtzberg, J.; Tan, S.

    2015-01-01

    Cerebral palsy (CP) has significant impact on both patients and society but therapy is limited. Human umbilical cord blood cells (HUCBC), containing various stem and progenitor cells, have been used to treat various brain genetic conditions. In small animal experiments, HUCBC have improved outcomes after hypoxic-ischemic injury. Clinical trials using HUCBC are underway testing feasibility, safety and efficacy for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model of CP after acute changes secondary to hypoxic-ischemic (H-I) injury had subsided. Following uterine ischemia at 70% gestation, we infused HUCBC to newborn rabbit kits with either mild or severe neurobehavioral changes. Infusion of high dose HUCBC, 5x106 cells, dramatically altered the natural history of the injury alleviating the abnormal phenotype including posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed lesser but still significant improvement. The swimming test however showed that joint function did not restore to naïve control function in either group. Tracing HUCBCs with either MRI biomarkers or PCR for human DNA found little penetration of HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial effects were not due to cellular integration or direct proliferative effects but rather to paracrine signaling. This is the first study to show that HUCBC improve motor performance in a dose-dependent manner perhaps by improving compensatory repair processes. PMID:25791742

  8. Biologic Response to Carbonated Hydroxyapatite Associated with Orthopedic Device: Experimental Study in a Rabbit Model

    PubMed Central

    Saoudi, Mongi; Badraoui, Riadh; Rebai, Tarek; Oudadesse, Hassane; Ellouz, Zoubaier; Keskese, Hassib; El Feki, Abdelfattah; El Feki, Hafed

    2012-01-01

    Background Carbonated hydroxyapatite (CHA) and related calcium phosphates have been studied for many years as implant materials due to their similarity with the mineral phase of bone. The main limitation of CHA ceramics as well as other bioactive materials is that they have poor mechanical proprieties. It is thought that the mechanical device can cause an increase in metabolic activity and bone healing. In this study we investigated the reactivity and tissue behaviour of implanted CHA biomaterial reinforced by mini external fixator. Methods The evaluation of biomaterial biocompatibility and osteogenesis was performed on a rabbit model over a period of 6 weeks by radiological, histological and scanning electron microscopy (SEM) coupled with energy dispersive X-ray SEM-energy-dispersive X-ray (EDX) analysis. Results While rabbits treated with CHA exhibited more bone formation, and fibrous tissue was observed when empty bone defects were observed. EDX analysis detected little calcium and phosphorus on the surface of the bone that was not implanted, while high content of calcium (62.7%) and phosphorus (38%) was found on the interface bone cement. Conclusions Bone repairing showed that the mini external fixator stimulated the ossification which was pushed when grafted by CHA. This effect may play an important role in the prevention of implant loosening. PMID:23109978

  9. A novel method for right one-lung ventilation modeling in rabbits

    PubMed Central

    Xu, Ze-Ping; Gu, Lian-Bing; Bian, Qing-Ming; Li, Peng-Yi; Wang, Li-Jun; Chen, Xiao-Xiang; Zhang, Jing-Yuan

    2016-01-01

    There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, P<0.05; 33±9 min in clamp group, P<0.001); more blood loss was observed in clamp group (11.7±2.8 ml), compared with the other two OLV groups (2.3±0.5 ml in deep intubation group, P<0.001; 2.1±0.6 ml in blocker group, P<0.001). The first-time and final success rate of modeling showed no differences among the three OLV groups. Deep intubation of the self-made bronchial blocker into the left main bronchus is an easy, effective and reliable method to establish a right-OLV model in rabbits. PMID:27446346

  10. Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a.

    PubMed Central

    Rabbani, G H; Albert, M J; Rahman, H; Islam, M; Mahalanabis, D; Kabir, I; Alam, K; Ansaruzzaman, M

    1995-01-01

    Rabbits are not usually susceptible to intestinal Shigella infection without extensive pretreatment, including starvation and administration of antimicrobial, antimotility, and toxic agents (carbon tetrachloride). Most animals infected this way die rapidly and do not always develop colonic lesions and signs of dysentery. We describe here a successful experimental infection in the adult rabbit which does not require preparatory treatment and which reproduced characteristic features of human shigellosis. Unstarved, untreated adult rabbits were infected by direct inoculation of virulent Shigella flexneri 2a (10 ml of 10(7) bacteria per ml) into the proximal colon after ligation of the distal cecum (cecal bypass). Within 24 h of infection, most inoculated animals consistently developed clinical dysentery, characterized by liquid stool mixed with mucus and blood, leukocytosis, anorexia, and weight loss. Histologically, there were edema, exudation, superficial ulceration, and polymorphonuclear infiltrations in the lamina propria; crypt abscess formation; focal hemorrhages; and the presence of immunohistochemically stained S. flexneri in the colonic mucosa. Successful bacterial colonization was indicated by the isolation of the challenge strain of S. flexneri 2a from the colonic contents. None of the control rabbits challenged with nonvirulent S. flexneri or without cecal bypass developed dysentery or colitis. We conclude that successful Shigella infection can be induced by direct colonic inoculation with virulent S. flexneri 2a in adult rabbits without starvation and pretreatment. The colitis is dependent on the virulence of the bacteria and on the cecal bypass. This model should be useful in studies of the immunopathogenesis of Shigella infection. PMID:7591070

  11. A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections

    PubMed Central

    2013-01-01

    Background Implant infection is one of the most severe complications within the field of orthopaedic surgery, associated with an enormous burden for the healthcare system. During the last decades, attempts have been made to lower the incidence of implant-related infections. In the case of cemented prostheses, the use of antibiotic-containing bone cement can be effective. However, in the case of non-cemented prostheses, osteosynthesis and spinal surgery, local antibacterial prophylaxis is not a standard procedure. For the development of implant coatings with antibacterial properties, there is a need for a reliable animal model to evaluate the preventive capacity of such coatings during a specific period of time. Existing animal models generally present a limited follow-up, with a limited number of outcome parameters and relatively large animal numbers in multiple groups. Methods To represent an early post-operative implant infection, we established an acute tibial intramedullary nail infection model in rabbits by contamination of the tibial nail with 3.8 × 105 colony forming units of Staphylococcus aureus. Clinical, haematological and radiological parameters for infection were weekly assessed during a 6-week follow-up with post-mortem bacteriological and histological analyses. Results S. aureus implant infection was confirmed by the above parameters. A saline control group did not develop osteomyelitis. By combining the clinical, haematological, radiological, bacteriological and histological data collected during the experimental follow-up, we were able to differentiate between the control and the infected condition and assess the severity of the infection at sequential timepoints in a parameter-dependent fashion. Conclusion We herein present an acute early post-operative rabbit implant infection model which, in contrast to previously published models, combines improved in-time insight into the development of an implant osteomyelitis with a relatively low

  12. The use of URYX for reversible vasectomy in a rabbit model.

    PubMed

    Naughton, Cathy K; Myles, Jonathan; Thomas, Anthony J

    2004-01-01

    harvested and examined for the presence of URYX. The inflammatory response of the wall and adventitia of the vas deferens was given a score (0-15) based on the sum of grades (0 = none, 1 = mild, 2 = moderate, and 3 = severe) for the following categories: foreign body giant cell reaction, granulation tissue, lymphocytes, eosinophils, and scarring, as evaluated by a single pathologist (J.M.). Vasal injection with 0.05 mL of URYX was not sufficient to cause occlusion. Both animals injected with 0.1 mL of URYX were effectively occluded. The injection of occluded vasa with DMSO did not dissolve the URYX plug in the vas lumen. There was no significant difference in vasal inflammatory response scores between vasal units treated with URYX only and vasal units in the vasectomy model. Vasal units subjected to URYX followed by DMSO demonstrated greater inflammatory response scores than vasal units treated with URYX followed by normal saline, URYX alone, or vasectomy. Epididymal and testicular histology remained unaffected in all vasal units in E1. The vasal units in E2 subjected to URYX followed by normal saline showed no histological abnormalities of the epididymis and testis. However, those vasal units subjected to URYX followed by DMSO in E2 showed evidence of adhesions, necrosis, and degenerating cells in the epididymis and a focal foreign body giant cell reaction in the testis. The bilateral vasal injection of URYX can result in azoospermia in the rabbit model. Reversal with subsequent DMSO injection was not achieved. A minimal inflammatory response of the vas deferens was observed with URYX injection alone; however, DMSO following URYX injection resulted in increased vasal inflammation, in addition to epididymal and testicular changes. PMID:15223843

  13. Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

    PubMed Central

    2014-01-01

    Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  14. Multi-event capture-recapture modeling of host-pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns.

    PubMed

    Santoro, Simone; Pacios, Isa; Moreno, Sacramento; Bertó-Moran, Alejandro; Rouco, Carlos

    2014-01-01

    Host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host-pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  15. Comparison of Two Synthetic Bone Graft Products in a Rabbit Posterolateral Fusion Model

    PubMed Central

    Fredericks, Douglas; Petersen, Emily B.; Watson, Nicole; Grosland, Nicole; Gibson-Corley, Katherine; Smucker, Joseph

    2016-01-01

    Background The drawbacks of iliac crest autograft as graft material for spine fusion are well reported. Despite continued modifications to improve bone healing capacity, the efficacy of synthetic graft materials as stand-alone replacements remains uncertain. The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographic, biomechanical and histological data on novel fusion materials. The objective of this study was to compare the spine fusion capability of two synthetic bone graft products in an established rabbit posterolateral spine fusion (PLF) model: Signafuse® Bioactive Bone Graft Putty and Actifuse® ABX. Methods Bilateral intertransverse spine fusion was performed at the L5-L6 transverse processes (TPs) of New Zealand White rabbits using either Signafuse or Actifuse ABX as the bone graft material. Bone remodeling and spine fusion were assessed at 6 and 12 weeks using radiographic, biomechanical and histological endpoints. Results Fusion rate by manual palpation at 6 weeks was greater for Signafuse (33%) compared to Actifuse ABX (0%), and equivalent in both groups at 12 weeks (50%). Biomechanical fusion rate based on flexion-extension data was 80% in Signafuse group and 44% for Actifuse ABX. Histology revealed a normal healing response in both groups. MicroCT and histomorphometric data at 6 weeks showed greater new bone formation in the Signafuse group compared to Actifuse ABX (p <0.05), with no differences detected at 12 weeks. Histological fusion scores were greater in the Signafuse group at 6 and 12 weeks, indicated by higher degree structural remodeling and tendency towards complete bridging of the fusion bed compared to the Actifuse ABX group. Conclusion Confirmed by several metrics, Signafuse outperformed Actifuse ABX as a standalone synthetic bone graft in an established PLF model, demonstrating greater rates of bone remodeling and spine fusion. The combination of 45

  16. Effects of Fluvastatin on Characteristics of Stellate Ganglion Neurons in a Rabbit Model of Myocardial Ischemia

    PubMed Central

    Cheng, Li-Jun; Li, Guang-Ping; Li, Jian; Chen, Yan; Wang, Xing-Hua

    2016-01-01

    Background: Stellate ganglion (SG) plays an important role in cardiovascular diseases. The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system. The aim of this research was to evaluate the effects of fluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia (MI). Methods: The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits. Using whole-cell patch clamp technique, we studied the characteristic changes of ion channels and action potentials (APs) in isolated SG neurons in control group (n = 20), MI group (n = 20) and fluvastatin pretreated group (fluvastatin group, n = 20), respectively. The protein expression of sodium channel in SG was determined by immunohistochemical analysis. Results: MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents. The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves, inactivation curves, and recovery curves after inactivation were changed in the MI group. The peak current densities of control group, MI group, and fluvastatin group (n = 10 in each group) were −71.77 ± 23.22 pA/pF, −126.75 ± 18.90 pA/pF, and −86.42 ± 28.30 pA/pF, respectively (F = 4.862, P = 0.008). Fluvastatin can decrease the current amplitude which has been increased by MI. Moreover, fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group. But the expression of sodium channel-associated protein (Nav1.7) had no significantly statistical difference among the three groups. The percentages of Nav1.7 protein in control group, MI group, and fluvastatin group (n = 5 in each group) were 21.49 ± 7.33%, 28.53 ± 8.26%, and 21.64 ± 2.78%, respectively (F = 1.495, P = 0.275). Moreover, MI reduced the electrical

  17. In vivo efficacy of moxifloxacin compared with cloxacillin and vancomycin in a Staphylococcus aureus rabbit arthritis experimental model.

    PubMed

    Grossi, Olivier; Caillon, Jocelyne; Arvieux, Cedric; Jacqueline, Cedric; Bugnon, Denis; Potel, Gilles; Hamel, Antoine

    2007-09-01

    We investigated the efficacies of moxifloxacin, cloxacillin, and vancomycin in a rabbit model of Staphylococcus aureus arthritis. No significant difference between therapeutic regimens was observed after a 7-day treatment. Oral moxifloxacin could be a suitable alternative to standard parenteral therapy for S. aureus arthritis. PMID:17576849

  18. Model for assessment of mobility of toes and healing of tendons in rabbits.

    PubMed

    Olmarker, Kjell; Ekström, Lars; Håkansson, Joakim; Nilsson, Elin; Wiig, Monica; Mahlapuu, Margit

    2010-12-01

    Repair of a transected flexor tendon will, despite careful technique and early rehabilitation, usually result in a restricted range of movement. This is mainly because adhesions form between the tendon and the surrounding structures. Our aim was to establish an experimental model in rabbits for future studies on new techniques to reduce the formation of adhesions after zone II repair of flexor tendons. In rabbits' hind paws the metatarsal bones II, IV, and V were removed and the flexor tendon was freed to the metatarsophalangeal (MTP) joint. The digits were secured in a specifically-designed biomechanical testing device comprising a servo-hydraulic actuator that was designed to apply controlled force or displacement. The tests were videotaped with a digital force-monitor behind the tested digit. Paper printouts from the recordings were obtained for 0, 0.5, 1, 2, 3, 4, and 5 Newton (N) and metatarsophalangeal, proximal interphalangeal, and distal interphalangeal, angles and distances between metatarsophalangeal joints and claws were measured. The tensile strength of the tendon was evaluated by a load-to-failure test. The continuous data obtained from the experiments were used to calculate functional stiffness at the selected forces. The model allows for unique continuous recordings of mobility of toes, thereby indirectly quantifying the presence of adhesions and the assessment of tensile strength. The data are reproducible, and there is little variation between the digits tested. The model is primarily intended to compare data among treated and non-treated digits of methods to limit the formation of adhesions after tendons have been repaired. PMID:21446803

  19. Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model

    PubMed Central

    Kim, Jung-Sun; Lee, Seul-Gee; Oh, Jaewon; Park, Se-Il; Hong, Sung-Yu; Kim, Sehoon; Lee, Sang-Hak; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

    2016-01-01

    Purpose Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. Conclusion These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis. PMID:27401639

  20. Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye

    PubMed Central

    ZHENG, WENJING; MA, MINGMING; DU, ERGANG; ZHANG, ZHENGWEI; JIANG, KELIMU; GU, QING; KE, BILIAN

    2015-01-01

    The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate-buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain-optical coherence tomography. Tear membrane break-up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription-quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultra-structure7 days after treatment. The percentages of apoptotic corneal- and Cj-ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly

  1. Rabbit models of cardiac mechano-electric and mechano-mechanical coupling.

    PubMed

    Quinn, T Alexander; Kohl, Peter

    2016-07-01

    Cardiac auto-regulation involves integrated regulatory loops linking electrics and mechanics in the heart. Whereas mechanical activity is usually seen as 'the endpoint' of cardiac auto-regulation, it is important to appreciate that the heart would not function without feed-back from the mechanical environment to cardiac electrical (mechano-electric coupling, MEC) and mechanical (mechano-mechanical coupling, MMC) activity. MEC and MMC contribute to beat-by-beat adaption of cardiac output to physiological demand, and they are involved in various pathological settings, potentially aggravating cardiac dysfunction. Experimental and computational studies using rabbit as a model species have been integral to the development of our current understanding of MEC and MMC. In this paper we review this work, focusing on physiological and pathological implications for cardiac function. PMID:27208698

  2. Quantitative Analysis of Disc Degeneration Using Axial T2 Mapping in a Percutaneous Annular Puncture Model in Rabbits

    PubMed Central

    Chai, Jee Won; Lee, Joon Woo; Kim, Su-Jin; Hong, Sung Hwan

    2016-01-01

    Objective To evaluate T2 relaxation time change using axial T2 mapping in a rabbit degenerated disc model and determine the most correlated variable with histologic score among T2 relaxation time, disc height index, and Pfirrmann grade. Materials and Methods Degenerated disc model was made in 4 lumbar discs of 11 rabbits (n = 44) by percutaneous annular puncture with various severities of an injury. Lumbar spine lateral radiograph, MR T2 sagittal scan and MR axial T2 mapping were obtained at baseline and 2 weeks and 4 weeks after the injury in 7 rabbits and at baseline and 2 weeks, 4 weeks, and 6 weeks after the injury in 4 rabbits. Generalized estimating equations were used for a longitudinal analysis of changes in T2 relaxation time in degenerated disc model. T2 relaxation time, disc height index and Pfirrmann grade were correlated with the histologic scoring of disc degeneration using Spearman's rho test. Results There was a significant difference in T2 relaxation time between uninjured and injured discs after annular puncture. Progressive decrease in T2 relaxation time was observed in injured discs throughout the study period. Lower T2 relaxation time was observed in the more severely injured discs. T2 relaxation time showed the strongest inverse correlation with the histologic score among the variables investigated (r = -0.811, p < 0.001). Conclusion T2 relaxation time measured with axial T2 mapping in degenerated discs is a potential method to assess disc degeneration. PMID:26798222

  3. Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control.

    PubMed

    Suen, Willy W; Uddin, Muhammad J; Wang, Wenqi; Brown, Vienna; Adney, Danielle R; Broad, Nicole; Prow, Natalie A; Bowen, Richard A; Hall, Roy A; Bielefeldt-Ohmann, Helle

    2015-01-01

    The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

  4. Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control

    PubMed Central

    Suen, Willy W.; Uddin, Muhammad J.; Wang, Wenqi; Brown, Vienna; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2015-01-01

    The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

  5. LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

    NASA Technical Reports Server (NTRS)

    Puglisi, J. L.; Bers, D. M.

    2001-01-01

    An interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.

  6. Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model.

    PubMed

    D'Este, Matteo; Sprecher, Christoph Martin; Milz, Stefan; Nehrbass, Dirk; Dresing, Iska; Zeiter, Stephan; Alini, Mauro; Eglin, David

    2016-06-01

    Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel for cartilage repair obtained by covalently grafting poly(N-isopropylacrylamide) to hyaluronan, to give a brush co-polymer HpN. The gel is fluid at room temperature and becomes gel at body temperature. In this pilot study HpN safety and repair response were evaluated in an osteochondral defect model in rabbit. Follow-up was of 1 week and 12 weeks and the empty defect served as a control, for a total of four experimental groups. At 12 weeks the defect sites were evaluated macroscopically and histologically. Local lymph nodes, spleen, liver, and kidneys were analyzed for histopathological evaluation. HpN could be easily injected and remained into the defect throughout the study. The macroscopic score was statistically superior for HpN versus empty. Histological score gave opposite trend but not statistically significant. A slight tissue reaction was observed around HpN, however, vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with fairly good continuity and lateral integration into the existing articular cartilage was observed in all cases. No signs of local or systemic acute or subacute toxicity were observed. In conclusion, HpN is easily injectable, remains into an osteochondral defect within a moving synovial joint, is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1469-1478, 2016. PMID:26833870

  7. Effect of Hydroxyapatite porous characteristics on healing outcomes in rabbit posterolateral spinal fusion model.

    PubMed

    Motomiya, Makoto; Ito, Manabu; Takahata, Masahiko; Kadoya, Ken; Irie, Kazuharu; Abumi, Kuniyoshi; Minami, Akio

    2007-12-01

    Hydroxyapatite (HA) has been commonly used as a bone graft substitute in various kinds of clinical fields. To improve the healing capability of HA, many studies have been performed to reveal its optimal structural characteristics for better healing outcomes. In spinal reconstruction surgery, non-interconnected porous HAs have already been applied as a bone graft extender in order to avoid autogenous bone harvesting. However, there have been few experimental studies regarding the effects of the structural characteristics of HA in posterolateral lumbar intertransverse process spine fusion (PLF). The aims of this study were to investigate the effect of HA porous characteristics on healing outcomes in a rabbit PLF model in order to elucidate appropriate structural characteristics of HA as a bone graft extender. Thirty-six adult female Japanese White rabbits underwent bilateral intertransverse process fusion at the level of L5-6 without internal fixation. We prepared three types of HA with different porosities: HA with 15% porosity (HA15%), HA with 50% porosity (HA50%), and HA with 85% porosity (HA85%), all of which were clinically available materials. The HA15% and HA50% had few interconnecting pores, whereas the HA85%, which was a recently developed material, had abundant interconnecting pores. All rabbits were randomly divided into the following four groups according to the grafted materials: (1) HA15% + autogenous bone, (2) HA50% + autogenous bone, (3) HA85% + autogenous bone, (4) pure autogenous bone graft. The animals were euthanized at 5 weeks after surgery, and post-mortem analyses including biomechanical testing, radiographical and histological evaluations were performed. There was no statistically significant difference in either fusion rate and/or bending stiffness among the three HA groups. However, in histological and radiological analyses, both bone ingrowth rate and direct bone bonding rate in the HA85% group were significantly higher than those in the HA

  8. Transauricular balloon angioplasty in rabbit thoracic aorta: a novel model of experimental restenosis

    PubMed Central

    2014-01-01

    Background The aim of this study was to demonstrate a percutaneous transauricular method of balloon angioplasty in high-cholesterol fed rabbits, as an innovative atherosclerosis model. Methods Twenty male New Zealand rabbits were randomly divided into two groups of ten animals, as follows: atherogenic diet plus balloon angioplasty (group A) and atherogenic diet alone (group B). Balloon angioplasty was performed in the descending thoracic aorta through percutaneous catheterization of the auricular artery. Eight additional animals fed regular diet were served as long term control. At the end of 9 week period, rabbits were euthanized and thoracic aortas were isolated for histological, immunohistochemical and biochemical analysis. Results Atherogenic diet induced severe hypercholesterolemia in both group A and B (2802 ± 188.59 and 4423 ± 493.39 mg/dl respectively) compared to the control animals (55.5 ± 11.82 mg/dl; P < 0.001). Group A atherosclerotic lesions appeared to be more advanced histologically (20% type IV and 80% type V) compared to group B lesions (50% type III and 50% type IV). Group A compared to group B atherosclerotic lesions demonstrated similar percentage of macrophages (79.5 ± 9.56% versus 84 ± 12.2%; P = 0.869), more smooth muscle cells (61 ± 14.10% versus 40.5 ± 17.07; P = 0.027), increased intima/media ratio (1.20 ± 0.50 versus 0.62 ± 0.13; P = 0.015) despite the similar degree of intimal hyperplasia (9768 ± 1826.79 μm2 versus 12205 ± 8789.23 μm2; P = 0.796), and further significant lumen deterioration (23722 ± 4508.11 versus 41967 ± 20344.61 μm2; P = 0.05) and total vessel area reduction (42350 ± 5819.70 versus 73190 ± 38902.79 μm2; P = 0.022). Group A and B animals revealed similar nitrated protein percentage (P = NS), but significantly higher protein nitration compared to control group (P < 0.01; P < 0.01, respectively

  9. Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer

    PubMed Central

    Maeng, Jin Hee; Lee, Eunhye

    2013-01-01

    In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. Endoscopic mucosal resection (EMR) is frequently performed for treatment of early gastric cancers. This procedure inevitably leads to ulcers and bleeding. Bleeding control is the major concern in endoscopic mucosectomy, and some endoscopic hemostatic agents are currently under clinical and preclinical studies. MRU was developed as a model for these induced ulcers and the evaluation of the healing process. The clinical relevancy of those models was compared with that of rat models. Progressive healing was observed for 7 days based on histology. Rabbit models demonstrate round, deep ulcers with clear margins and well-defined healing stages that were difficult to define in rat models. PMID:23825482

  10. Gamma-Irradiated Sterile Cornea for Use in Corneal Transplants in a Rabbit Model

    PubMed Central

    Yoshida, Junko; Heflin, Thomas; Zambrano, Andrea; Pan, Qing; Meng, Huan; Wang, Jiangxia; Stark, Walter J.; Daoud, Yassine J.

    2015-01-01

    Purpose: Gamma irradiated corneas in which the donor keratocytes and endothelial cells are eliminated are effective as corneal lamellar and glaucoma patch grafts. In addition, gamma irradiation causes collagen cross inking, which stiffens collagen fibrils. This study evaluated gamma irradiated corneas for use in corneal transplantations in a rabbit model comparing graft clarity, corneal neovascularization, and edema. Methods: Penetrating keratoplasty was performed on rabbits using four types of corneal grafts: Fresh cornea with endothelium, gamma irradiated cornea, cryopreserved cornea, and fresh cornea without endothelium. Slit lamp examination was performed at postoperative week (POW) one, two, and four. Corneal clarity, edema, and vascularization were graded. Confocal microscopy and histopathological evaluation were performed. A P < 0.05 was statistically significant. Results: For all postoperative examinations, the corneal clarity and edema were statistically significantly better in eyes that received fresh cornea with endothelium compared to the other three groups (P < 0.05). At POW 1, gamma irradiated cornea scored better than the cryopreserved and fresh cornea without endothelium groups in clarity (0.9 vs. 1.5 and 2.6, respectively), and edema (0.6 vs. 0.8 and 2.0, respectively). The gamma irradiated corneas, cryopreserved corneas and the fresh corneas without endothelium, developed haze and edema after POW 2. Gamma irradiated cornea remained statistically significantly clearer than cryopreserved and fresh cornea without endothelium during the observation period (P < 0.05). Histopathology indicated an absence of keratocytes in gamma irradiated cornea. Conclusion: Gamma irradiated corneas remained clearer and thinner than the cryopreserved cornea and fresh cornea without endothelium. However, this outcome is transient. Gamma irradiated corneas are useful for lamellar and patch grafts, but cannot be used for penetrating keratoplasty. PMID:26180475

  11. Biochemical Basis of Vocal Fold Mobilization After Microflap Surgery in a Rabbit Model

    PubMed Central

    Mitchell, Joshua R.; Kojima, Tsuyoshi; Wu, Hongmei; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objectives/Hypothesis To investigate phonation-related extracellular matrix (ECM) changes in the vocal fold lamina propria after microflap surgery using an in vivo rabbit phonation model. Study Design Prospective animal study. Methods Twenty-four New Zealand White rabbits were used in this study. Quantitative polymerase chain reaction and immunohistochemistry were used to investigate alterations in vocal fold ECM proinflammatory and profibrotic gene, and protein expression from a control group of animals receiving a microflap without phonation and a separate group of animals receiving experimentally induced phonation on postmicroflap days 0, 3, and 7. Results IHC demonstrated the highest concentration of CD45 in vocal folds on postoperative day 0. Staining for CD45 was absent by postoperative day 7, with no differences in CD45 staining between groups. Fibronectin gene expression increased significantly on postoperative day 3 in the control and experimentally induced phonation groups, with maximal staining of fibronectin around the microflap incision on postoperative day 7. No alterations in cyclooxygenase-2, interleukin-1β, and transforming growth factor-β1 gene expression were observed between groups. Conclusions Results of the present study revealed an acute inflammatory response in the vocal fold at the time of microflap (day 0) and up to 3 days post-microflap. By post-operative day 3, staining of CD45 positive cells decreased, with essentially no evidence of inflammation by post-operative day 7. With the end of the acute inflammatory response occurring around day 3, these data may provide support for mobilizing tissue after inflammation has subsided and the process of active tissue remodeling has ensued (days 3–7). PMID:23775575

  12. Does Low-intensity pulsed ultrasound treatment repair articular cartilage injury? A rabbit model study

    PubMed Central

    2014-01-01

    Background Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo. Methods We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated. Results The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment. Conclusion LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study. PMID:24507771

  13. Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia.

    PubMed

    Vuckovic, Aline; Herber-Jonat, Susanne; Flemmer, Andreas W; Strizek, Brigitte; Engels, Alexander C; Jani, Jacques C

    2016-04-01

    Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model. Rabbit fetuses with surgically induced CDH at day 23 of gestation were randomized at day 28 for an intratracheal injection of BAY 41-2272 or vehicle. After term delivery (day 31), lung mechanics, right ventricular pressure, and serum NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) levels were measured. After euthanasia, lungs were processed for biological or histological analyses. Compared with untouched fetuses, the surgical creation of CDH reduced the lung-to-body weight ratio, increased mean terminal bronchial density, and impaired lung mechanics. Typical characteristics of PH were found in the hypoplastic lungs, including increased right ventricular pressure, higher serum NT-proBNP levels, thickened adventitial and medial layers of pulmonary arteries, reduced capillary density, and lower levels of endothelial nitric oxide synthase. A single antenatal instillation of BAY 41-2272 reduced mean right ventricular pressure and medial thickness of small resistive arteries in CDH fetuses. Capillary density, endothelial cell proliferation, and transcripts of endothelial nitric oxide synthase increased, whereas airway morphometry, lung growth, and mechanics remained unchanged. These results suggest that pharmacological activation of soluble guanylate cyclase may provide a new approach to the prenatal treatment of PH associated with CDH. PMID:26873974

  14. Photopic negative response in diagnosis of glaucoma: an experimental study in glaucomatous rabbit model

    PubMed Central

    ElGohary, Amal A.; Elshazly, Laila Hassan M.

    2015-01-01

    AIM To determine whether the photopic negative response (PhNR) elicited by transient white flash on white background is characterizing for glaucoma model in rabbits. METHODS Glaucoma was induced in twelve rabbits by subconjunctival injection of 0.05 mL of betamethasone in right eyes (each 1 mL contain betamethasone dipropionate 5 mg and betamethasone sodium phosphate 2 mg).The intraocular pressure (IOP), electroretinogram (ERG) and visual evoked potential (VEP) were measured successively prior and on the 3, 7d, two weeks and four weeks postglaucoma induction. After four weeks, the animals were sacrificed and the globes were histopathologically examined. RESULTS The IOP increased significantly after one week (P=0.0001), then it gradually returned to the control level. In ERG examination, the means of a and b wave amplitude and latency were not affected significantly. PhNR amplitude decreased significantly within one week (P=0.0001), but its latency was not affected significantly (P=0.132). The means of VEP latency and amplitude were significantly affected after two weeks and four weeks of glaucoma induction (P=0.0001 and 0.02, respectively). The histopathologic examination of the globes showed reduced number of cells in the retinal ganglion cell layer with multiple vacuoles in the retinal nerve fibre layer.There was significant positive correlation between ganglion cell layer cells and PhNR amplitude (r=0.8, P=0.002). CONCLUSION The rise in IOP resulted in irreversible changes or incomplete recovery of VEP and PhNR amplitude. Both PhNR and VEP represented good additional tools in early diagnosis of glaucoma. PMID:26085991

  15. Effects of trace element supplementation on the inflammatory response in a rabbit model of major trauma.

    PubMed

    Yuan, Wan-an; Yu, Xiao-jun; Liu, Fu-Qi; Wang, Hai-peng; Wang, Dian; Lai, Xiao-ping

    2010-01-01

    Patients with a severe trauma exhibit a strong oxidative stress, an intense inflammatory response, and long-lasting hypermetabolism, all of which are proportional to the severity of injury. In this study, we investigated the impact of trace element (TE) supplementation on the inflammatory response in an animal model of major trauma. New Zealand White rabbits were randomly assigned as a control group (n=5) and an experimental group (n=70) that, after receiving a major trauma, was subdivided into Trauma-Control (n=35) and Trauma-TE (n=35) groups. Systemic inflammatory response syndrome (SIRS) was observed in 40 out of 70 rabbits with a trauma, with a higher incidence in the Trauma-Control group (88.6%; 31/35) than the Trauma-TE group (28.6%; 10/35) (p<0.01). The mortality rate was significantly different between the Trauma-Control and the Trauma-TE groups; (34% vs. 8%; p<0.01). There were significant post-trauma alterations in the levels of (1) serum and spleen zinc (Zn), copper (Cu), selenium (Se), and manganese (Mn), (2) serum AST and ALT, (3) serum interleukin-6/10, and (4) nuclear factor kappa binding (NF-kappaB) activity and the expression. TE supplementation: (1) improved blood urea nitrogen (BUN), and creatinine (Cr) levels, (2) stabilized IL-6/10 production, (3) decreased NF-kappaB p(65) production. Appropriate TE supplementation can improve the TE status, mitigate SIRS, and reduce the mortality due to multiple organ dysfunction syndromes (MODS)/multiple organ failure (MOF) after major trauma. PMID:20122578

  16. Intramuscular Cobinamide Sulfite in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    PubMed Central

    Brenner, Matthew; Kim, Jae G.; Mahon, Sari B.; Lee, Jangwoen; Kreuter, Kelly A.; Blackledge, William; Mukai, David; Patterson, Steve; Mohammad, Othman; Sharma, Vijay S.; Boss, Gerry R.

    2009-01-01

    Objective To determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. Background Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B12) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigated the use of intramuscular cobinamide sulfite to reverse cyanide toxicity induced physiologic changes in a sublethal cyanide exposure animal model. Methods New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous wave near infrared spectroscopy monitoring of tissue oxy- and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). Results Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system was in a mean of 1032 minutes in the control group and 9 minutes in the cobinamide group with a difference of 1023 minutes (95% confidence interval [CI] 116, 1874 minutes). In muscle tissue, recovery times were 76 and 24 minutes with a difference of 52 minutes (95% CI 7, 98min). Red blood cell cyanide levels returned towards normal significantly faster in cobinamide sulfite-treated animals than in control animals. Conclusions Intramuscular

  17. An Optical Section-Assisted In Vivo Rabbit Model for Capsular Bend and Posterior Capsule Opacification Investigation

    PubMed Central

    Zheng, Qian; Yu, Fang; Yu, Xiaoyu; Zhao, Yinying; Ding, Xixia; Zhu, Weigen; Li, Jin; Zhao, Yun-e

    2016-01-01

    Purpose To establish an optical section-assisted in vivo rabbit model for capsular bend and posterior capsule opacification (PCO) investigation. Methods A total of 10 rabbits underwent phacoemulsification surgery and intraocular lens (IOL) implantation. On the basis of the relationship between the anterior capsule and IOL, the rabbits were divided into complete overlap and incomplete overlap groups, in which six and four rabbits were included, respectively. The capsular bend optical sections were assessed using ultra-long scan depth optical coherence tomography (UL-OCT), and posterior capsule opacification was evaluated with slit lamp on postoperative day 3, 7, 14, and 28. In addition, histopathological section was used to verify the accuracy of capsular bend type captured by OCT in three rabbits. Results Based on the special animal model, six capsular bend types were observed, namely, anterior (A), middle (M), posterior (P), detachment (D), funnel (Fun) and furcate adhesion (Fur). On day 3, capsular bend began to form. On 14 days, the capsular bends were comprised of A, M and D types, which were almost maintained until day 28. Histopathological section findings were consistent with optical sectioning results. In the incomplete and complete groups, the earliest PCO within the optical zone were on day 7 and 28, respectively. The incomplete group exhibited higher incidence and faster PCO on day 7 (p = 0.038) and 14 (p = 0.002). Conclusions This animal model not only mimics capsular bend evolution and PCO processes but also produces OCT optical section images equivalent to and more repeatable than histopathology, thereby providing a promising method for the further investigations of PCO. PMID:26840405

  18. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model

    PubMed Central

    González, Juan C.; López, Catalina; Álvarez, María E.; Pérez, Jorge E.; Carmona, Jorge U.

    2016-01-01

    Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT. PMID:26781753

  19. The therapeutic effect of bevacizumab on plaque neovascularization in a rabbit model of atherosclerosis during contrast-enhanced ultrasonography

    PubMed Central

    Li, Yang; Zhu, Ying; Deng, Youbin; Liu, Yani; Mao, Yuhang; Wang, Junli; Sun, Jie

    2016-01-01

    The purpose of the study was to assess the therapeutic effect of the angiogenesis inhibitor bevacizumab on plaques of various stages in rabbit models using contrast-enhanced ultrasonography (CEUS). Abdominal aortic atherosclerosis was induced in 55 rabbits. Thirty-six randomly selected rabbits were divided into 2 groups according to the timing of the bevacizumab injection: an early-stage plaque group (Group ESP) and a later-stage plaque group (Group LSP). The remainder were considered the control group. Standard ultrasonography and CEUS imaging of the abdominal aorta were performed. The animals were euthanized after CEUS, and plaque specimens were harvested for histological staining of CD31. The control group exhibited a substantially higher enhanced intensity, a higher ratio of enhanced intensity in the plaque to that in the lumen, and an increased number of CD31-positive microvessels in the plaque sections than Groups ESP and LSP (P < 0.05 for all). A higher enhanced intensity (P = 0.044), a higher ratio of enhanced intensity in the plaque to that in the lumen (P = 0.023) and more CD31-positive microvessels in the plaque sections (P = 0.006) were found in Group LSP than in Group ESP. Bevacizumab demonstrated more advanced inhibition of neovascularization in early-stage plaques in rabbits. PMID:27452862

  20. New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

    PubMed Central

    Kurniawati, Tri; Siregar, Nurjati Chairani; Syahrurachman, Agus; Dilogo, Ismail Hadisubroto; Iskandriati, Diah; Fitri, Arni Diana

    2016-01-01

    Study Design Preliminary experimental study using a rabbit spondylitis model. Purpose To observe the ossification in a micro-environment containing live Mycobacterium tuberculosis transplanted with bone marrow stromal cells (BMSCs) in rabbits. Overview of Literature BMSCs differentiate to osteoblasts and then osteocytes during ossification. Mycobacterium tuberculosis does not affect BMSC growth in vitro. Methods Six rabbits were divided into two groups of three rabbits. One group was positive for spondylitis tuberculosis by culture, polymerase chain reaction (PCR), and histopathologically. The other group was positive by PCR and histopathologically. Both groups were treated using BMSC transplantation and anti-tuberculosis drugs. After 6 weeks, ossification was evaluated by enumerating the number of osteoblasts, osteocytes, and lesion level of calcium. Results Mean number of osteoblasts was 207.00±31.00 in the first group and 220.33±73.46 in the second group. Mean number of intra-lesions osteocytes was in the first and second group was 18.33±30.04 and 31.00±26.87, respectively. Mean calcium level in the first group and second group was 2.94%±0.89% and 2.51%±0.13%, respectively. Total ossification score in the first and second group was 31.00 and 25.67, respectively. Conclusions Mycobacterium tuberculosis provides support for new bone formation by stimulating intra-lesion calcium metabolism. The microscopic environment containing live Mycobacterium tuberculosis enhances ossification. PMID:26949451

  1. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model.

    PubMed

    González, Juan C; López, Catalina; Álvarez, María E; Pérez, Jorge E; Carmona, Jorge U

    2016-01-01

    Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1 from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT. PMID:26781753

  2. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model

    PubMed Central

    Lee, Jae Yeon; Son, Soo Jin; Son, Jun Sik; Kang, Seong Soo; Choi, Seok Hwa

    2016-01-01

    Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control), group 2 (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4 (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture. PMID:27042660

  3. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model.

    PubMed

    Lee, Jae Yeon; Son, Soo Jin; Son, Jun Sik; Kang, Seong Soo; Choi, Seok Hwa

    2016-01-01

    Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control), group 2 (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4 (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture. PMID:27042660

  4. Exploration of the wound healing effect of topical administration of nicotine in combination with collagen scaffold in a rabbit model.

    PubMed

    Masuoka, Hiromu; Morimoto, Naoki; Sakamoto, Michiharu; Ogino, Shuichi; Suzuki, Shigehiko

    2016-06-01

    Nicotine has been reported to prolong the wound healing; however, we showed that the topical application of 10(-4) M nicotine promoted murine wound healing. The objective of this study was to explore the wound healing effects of nicotine in combination with collagen scaffold using skin defects in rabbit. Three full-thickness skin defects 8 mm in diameter were made on the rabbit auricle. Artificial dermis was applied to the defects, and 10 μl of nicotine solution (10(-5), 10(-4), and10(-3) M), bFGF solution (0.5 μg/10 μl), and both bFGF and 10(-4) M nicotine solutions were injected into the artificial dermis once daily for 7 days. Rabbits were sacrificed on day 10, 15, or 20, and the wound healing process was evaluated. bFGF was superior in the formation of the dermis-like tissue and capillaries. In nicotine groups, the epithelial length and the dermis-like tissue formations in the 10(-4) M group were superior, in contrast, those were inhibited in the 10(-3) M group. The synergistic effect of bFGF and 10(-4) M nicotine was not confirmed. This study suggests that the topical application of 10(-4) M nicotine promoted wound healing in rabbit, but the effect was not apparent compared with murine models. PMID:26497310

  5. Corneal Stroma Regeneration with Acellular Corneal Stroma Sheets and Keratocytes in a Rabbit Model

    PubMed Central

    Ma, Xiao Yun; Zhang, Yun; Zhu, Dan; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie

    2015-01-01

    Acellular corneal stroma matrix has been used for corneal stroma engineering. However, because of its compact tissue structure, regrowth of keratocytes into the scaffold is difficult. Previously, we developed a sandwich model for cartilage engineering using acellular cartilage sheets. In the present study, we tested this model for corneal stroma regeneration using acellular porcine corneal stroma (APCS) sheets and keratocytes. Porcine corneas were decellularized by NaCl treatment, and the APCS was cut into 20-μm-thick sheets. A rabbit corneal stroma defect model was created by lamellar keratoplasty and repaired by transplantation of five pieces of APCS sheets with keratocytes. Six months after transplantation, transparent corneas were present in the experimental group, which were confirmed by anterior segment optical coherence tomography examination and transmittance examination. The biomechanical properties in the experimental group were similar to those of normal cornea. Histological analyses showed an even distribution of keratocytes and well-oriented matrix in the stroma layer in the experimental group. Together, these results demonstrated that the sandwich model using acellular corneal stroma sheets and keratocytes could be potentially useful for corneal stroma regeneration. PMID:26167895

  6. A rabbit model for evaluation of catheter-associated fungal biofilms.

    PubMed

    Chandra, Jyotsna; Long, Lisa; Ghannoum, Mahmoud A; Mukherjee, Pranab K

    2011-01-01

    Most cases of catheter-related bloodstream infections (CRBSIs) involve colonization of micro-organisms on catheter surfaces where they eventually become embedded in a biofilm. Fungal biofilm formation is studied using a number of techniques, involving the use of a wide variety of substrates and growth conditions. In vitro techniques involving use of confocal scanning laser/scanning electron microscopy, metabolic activity assay, dry weight measurements and antifungal susceptibility assays are increasingly used by investigators to quantify and evaluate biofilm morphology. However, there are not many in vivo models used to validate biofilm-associated infections. In this protocol, we describe clinically relevant rabbit model of C. albicans biofilm-associated catheter infection to evaluate the morphology, topography, and architecture of fungal biofilms. The methods described here can be completed in a typical laboratory setting. Evaluation of the formation of fungal biofilms on catheters in vivo, their analysis using scanning electron microscopy (SEM) and quantitative catheter culture (QCC) and treatment of biofilms using antimicrobial lock therapy can be completed using the described methods in ~20-25 days. This model has utility in evaluating the efficacy of lock solutions. In addition, it is a useful approach for characterizing/comparing the formation of biofilms by wild type and isogenic mutants including clinical isolates in vivo. This model can also be used for testing different biomaterials. PMID:21921676

  7. Molecular events linking cholesterol to Alzheimer’s disease and inclusion body myositis in a rabbit model

    PubMed Central

    Liu, Qing Yan; Koukiekolo, Roger; Zhang, Dong Ling; Smith, Brandon; Ly, Dao; Lei, Joy X; Ghribi, Othman

    2016-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by cognitive impairment and dementia, resulting from progressive synaptic dysfunction, loss and neuronal cell death. Inclusion body myositis (IBM) is a skeletal muscle degenerative disease, displaying progressive proximal and distal muscle weakness, in association with muscle fiber atrophy, degeneration and death. Studies have shown that the late onset version of AD (LOAD) and sporadic IBM (sIBM) in muscle share many pathological features, including the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins. High blood cholesterol is suggested to be a risk factor for LOAD. Many neuropathological changes of LOAD can be reproduced by feeding rabbits a 2% enriched cholesterol diet for 12 weeks. The cholesterol fed rabbit model also simultaneously develops sIBM like pathology, which makes it an ideal model to study the molecular mechanisms common to the development of both diseases. In the present study, we determined the changes of gene expression in rabbit brain and muscle during the progression of LOAD and sIBM pathology using a custom rabbit nucleotide microarray, followed by qRT-PCR analyses. Out of 869 unique transcripts screened, 47 genes showed differential expression between the control and the cholesterol-treated group during the 12 week period and 19 changed transcripts appeared to be common to LOAD and sIBM. The most notable changes are the upregulation of the hemoglobin gene family and the downregulation of the genes required for mitochondrial oxidative phosphorylation in both brain and muscle tissues throughout the time course. The significant overlap on the changes of gene expression in the brain and muscle of rabbits fed with cholesterol-enriched diet supports the notion that LOAD and sIBM may share a common etiology. PMID:27073745

  8. Anatomical features for an adequate choice of experimental animal model in biomedicine: II. Small laboratory rodents, rabbit, and pig.

    PubMed

    Lossi, Laura; D'Angelo, Livia; De Girolamo, Paolo; Merighi, Adalberto

    2016-03-01

    The anatomical features distinctive to each of the very large array of species used in today's biomedical research must be born in mind when considering the correct choice of animal model(s), particularly when translational research is concerned. In this paper we take into consideration and discuss the most important anatomical and histological features of the commonest species of laboratory rodents (rat, mouse, guinea pig, hamster, and gerbil), rabbit, and pig related to their importance for applied research. PMID:26527557

  9. A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure

    PubMed Central

    Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei

    2015-01-01

    Background The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Methods Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. Results No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients’ mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. Conclusions We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation

  10. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    PubMed Central

    Kaempfen, Alexandre; Todorov, Atanas; Güven, Sinan; Largo, René D.; Jaquiéry, Claude; Scherberich, Arnaud; Martin, Ivan; Schaefer, Dirk J.

    2015-01-01

    The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous “incubation” (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed. PMID:26053395

  11. Validation, reliability, and complications of a tethering scoliosis model in the rabbit.

    PubMed

    Kallemeier, Patricia M; Buttermann, Glenn R; Beaubien, Brian P; Chen, Xinqian; Polga, David J; Lew, William D; Wood, Kirkham B

    2006-04-01

    This study was conducted to refine a small animal model of scoliosis, and to quantify the deformities throughout its growth period. Subcutaneous scapula-to-contralateral pelvis tethering surgery was selected due to its minimally invasive nature and potential applicability for a large animal model. The procedure was performed in 7-week-old New Zealand white rabbits. Group A animals (n=9) underwent the tethering procedure with a suture that spontaneously released. Group B animals (n=17) had the identical procedure with a robust tether and pelvic fixation, which was maintained for 2 months during growth. All animals developed immediate post-operative scoliosis with a Cobb angle of 23 degrees (range, 6-39 degrees) in group A and 59 degrees (range, 24-90 degrees) in group B animals. During the 2 month post-tethering, group A animals lost their tether and scoliosis resolved, whereas all animals in group B maintained their tether until scheduled release at which time the mean scoliosis was 62 degrees. Immediately after tether release, group B scoliosis decreased to a mean 53 degrees. Over the following 4 months of adolescent growth, the scoliosis decreased to a mean of 43 degrees at skeletal maturity; the decrease usually occurred in animals with less than 45 degrees curves at tether release. Radiographs revealed apical vertebral wedging (mean 19 degrees ) in all group B animals. Sagittal spinal alignment was also assessed, and for group B animals, the scoliotic segment developed mild to moderate kyphosis (mean 28 degrees) and torsional deformity, but the kyphosis resolved by 4 months after tether-release. Complications specific to this technique included a high rate of transient scapulothoracic dissociation and cases of cor pulmonale. In conclusion, this tethering technique in immature rabbits consistently produced scoliosis with vertebral wedging when the tether was intact through the first 2 months of the protocol. The transient exaggeration of kyphosis suggests that

  12. Vasodilator effects of nebivolol in a rat model of hypertension and a rabbit model of congestive heart failure.

    PubMed

    de Groot, Annemieke A; Mathy, Marie-Jeanne; van Zwieten, Pieter A; Peters, Stephan L M

    2007-07-01

    Both hypertension and congestive heart failure are characterized by a reduced vasodilatory capacity. In both conditions, the impairment of endothelial function is mainly the result of a reduced nitric oxide availability. The highly beta1-selective third-generation adrenoceptor blocker nebivolol displays additional endothelium-dependent vasodilating actions in humans as well as in animal models. In this study, we investigated whether these vasodilating properties of nebivolol are preserved in conditions with endothelial dysfunction. The vasodilatory effects of nebivolol were compared with those of the muscarinic agonist methacholine in isolated aortic rings obtained from spontaneous hypertensive rats and rabbits with experimental heart failure. The methacholine-induced responses were attenuated in aortic rings from both spontaneous hypertensive rats and congestive heart failture rabbits (42+/-6% and 25+/-3% vs. 89+/-3% and 54+/-7% for controls, respectively; P<0.05, n=6-13), indicating an endothelial dysfunction in these preparations. In contrast, nebivolol-induced vasorelaxation remained unaffected in both preparations when compared to control preparations (40+/-12% and 43+/-6% vs. 52+/-8% and 50+/-13% for controls, respectively; P>0.05, n=6-13). These results implicate that the favorable hemodynamic profile of nebivolol may be preserved in patients with hypertension or congestive heart failure despite an impaired endothelial function. PMID:17666916

  13. Prevention of Ocular Scarring After Glaucoma Filtering Surgery Using the Monoclonal Antibody LT1009 (Sonepcizumab) in a Rabbit Model

    PubMed Central

    Lukowski, Zachary L.; Min, Jeff; Beattie, Ashley R.; Meyers, Craig A.; Levine, Monica A.; Stoller, Glenn; Schultz, Gregory S.; Samuelson, Don A.; Sherwood, Mark B.

    2013-01-01

    Purpose Excessive scarring leading to failure of the filtering bleb continues to be a major problem after glaucoma filtration surgery. This study examines the antifibrotic effects of the anti-S1P monoclonal antibody LT1009 (Sonepcizumab) in prolonging bleb survival in a rabbit model of glaucoma filtering surgery. Methods The frequency of LT1009 dosage was determined initially using an enzyme-linked immunosorbent assay assay measuring LT1009 eye tissue retention in 6 New Zealand White rabbits. A further 21 New Zealand White rabbits underwent glaucoma filtering surgery. Bleb tissues were observed and compared clinically and histologically. The duration of bleb elevation was compared among LT1009, balanced saline solution (BSS) negative control, and mitomycin-C (MMC)-positive control. Results The mean duration of bleb survival was 28.5 ± 8.5 days for rabbits receiving injections of LT1009, 21.0 ± 5.6 days for those receiving injections of BSS, and 33.8 ± 5.6 days for rabbits receiving MMC. Analysis of variance with post hoc testing suggests a statistically significant trend of improvement in bleb duration for LT1009 when compared with BSS controls. Non-painful, upper eyelid edema was noted after 5 injections of LT1009, which resolved over a 10-day period. MMC eyes developed avascular conjunctivas with areas of thinning and sparse cellularity, whereas the conjunctiva of LT1009 and BSS eyes remained relatively normal. Conclusions The monoclonal antibody LT1009 demonstrated a longer duration of bleb elevation than BSS control without adverse conjunctival effects associated with MMC. However, after multiple doses LT1009 use was associated with short-term upper eyelid edema. PMID:21946553

  14. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

    PubMed Central

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

  15. Posterolateral spinal fusion in a rabbit model using a collagen–mineral composite bone graft substitute

    PubMed Central

    Vizesi, F.; Cornwall, G. B.; Bell, D.; Oliver, R.; Yu, Y.

    2009-01-01

    Choosing the appropriate graft material to participate in the healing process in posterolateral spinal fusion continues to be a challenge. Combining synthetic graft materials with bone marrow aspirate (BMA) and autograft is a reasonable treatment option for surgeons to potentially reduce or replace the need for autograft. FormaGraft, a bone graft material comprising 12% bovine-derived collagen and 88% ceramic in the form of hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP) was evaluated in three possible treatment modalities for posterior spinal fusion in a standard rabbit model. These three treatment groups were FormaGraft alone, FormaGraft soaked in autogenous BMA, and FormaGraft with BMA and iliac crest autograft. No statistically demonstrable benefits or adverse effects of the addition of BMA were found in the current study based on macroscopic, radiology or mechanical data. This may reflect, in part, the good to excellent results of the collagen HA/TCP composite material alone in a well healing bony bed. Histology did, however, reveal a benefit with the use of BMA. Combining FormaGraft with autograft and BMA achieved results equivalent to autograft alone. The mineral and organic nature of the material provided a material that facilitated fusion between the transverse processes in a standard preclinical posterolateral fusion model. PMID:19475437

  16. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    PubMed Central

    Ibarra, R.; Dazard, J-E.; Sandlers, Y.; Rehman, F.; Abbas, R.; Kombu, R.; Zhang, G-F.; Brunengraber, H.; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT−) to samples from (LG+/LG−) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT−) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined. PMID:24723740

  17. Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

    PubMed

    Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang; Zhang, Changqing

    2013-07-01

    The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli. PMID:23629702

  18. Gentamicin-Loaded Borate Bioactive Glass Eradicates Osteomyelitis Due to Escherichia coli in a Rabbit Model

    PubMed Central

    Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang

    2013-01-01

    The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli. PMID:23629702

  19. Development of the Lacrimal Apparatus in the Rabbit (Oryctolagus cuniculus) and Its Potential Role as an Animal Model for Humans

    PubMed Central

    Rehorek, S. J.; Holland, J. R.; Johnson, J. L.; Caprez, J. M.; Cray, J.; Mooney, M. P.; Hillenius, W. J.; Smith, T. D.

    2011-01-01

    Rabbits have been proposed as a model organism for the human lacrimal apparatus (LA), including the nasolacrimal duct (NLD), based principally on comparative studies of adult morphology; however, little is known about its development. The NLD first appears as an incomplete primordium in the subcutaneous region of the primordial eyelid and subsequently elongates to reach the naris. One posterior and three anterior orbital glands are present fetally although one of the anterior glands is soon lost. The NLD follows a tortuous path and passes through a bony canal consisting of lacrimal, maxilla, and maxilloturbinal bones at different regions. Although early developmental similarities exist to haplorhine primates, the narial opening of the NLD resembles strepsirrhines. This distinction, along with the ductal and glandular differences at the orbital end of the NLD, indicates that rabbits may be a poor model for LA drainage in primates, specifically humans. PMID:22567296

  20. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

    PubMed Central

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-01-01

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema. PMID:26160987

  1. Endovascular image-guided treatment of in-vivo model aneurysms with asymmetric vascular stents (AVS): evaluation with time-density curve angiographic analysis and histology

    PubMed Central

    Dohatcu, A.; Ionita, C. N.; Paciorek, A.; Bednarek, D. R.; Hoffmann, K. R.; Rudin, S.

    2008-01-01

    In this study, we compare the results obtained from Time-Density Curve (TDC) analysis of angiographic imaging sequences with histological evaluation for a rabbit aneurysm model treated with standard stents and new asymmetric vascular stents (AVS) placed by image-guided endovascular deployment. AVSs are stents having a low-porosity patch region designed to cover the aneurysm neck and occlude blood flow inside. To evaluate the AVSs, rabbits with elastase-induced aneurysm models (n=20) were divided into three groups: the first (n=10) was treated with an AVS, the second (n=5) with a non-patch standard coronary stent, and third was untreated as a control (n=5). We used TDC analysis to measure how much contrast media entered the aneurysm before and after treatment. TDCs track contrast-media-density changes as a function of time over the region of interest in x-ray DSA cine-sequences. After 28 days, the animals were sacrificed and the explanted specimens were histologically evaluated. The first group showed an average reduction of contrast flow into the aneurysm of 95% after treatment with an AVS with fully developed thrombus at 28 days follow-up. The rabbits treated with standard stents showed an increase in TDC residency time after treatment and partial-thrombogenesis. The untreated control aneurysms displayed no reduction in flow and were still patent at follow-up. The quantitative TDC analysis findings were confirmed by histological evaluation suggesting that the new AVS has great potential as a definitive treatment for cerebro-vascular aneurysms and that angiographic TDC analysis can provide in-vivo verification. PMID:18958295

  2. Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

    NASA Astrophysics Data System (ADS)

    Makale, Milan Theodore

    This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

  3. 99m T c-DTPA Study to Validate an Experimental Model of Ureteral Obstruction in Rabbits: Preliminary Results

    PubMed Central

    de Lima, Marcelo Lopes; Bertti, Rodolfo; Moro, Juliano César; Coltro Neto, Fábio; Miyaoka, Ricardo; Fregonesi, Adriano; de Lima, Mariana da Cunha Lopes; Ramos, Celso Darío

    2013-01-01

    Objective. To create a ureteral obstruction experimental model that can be proved through 99mTc-DTPA renal scintigraphy and histopathological studies, without causing total renal function loss. Materials and Methods. Ten New Zealand white rabbits were submitted to a surgical experiment to create a model of unilateral obstruction to urinary flow. Surgery procedure provided unilateral ureteral obstruction (left kidney) to urinary flow and posteriorly was evaluated by 99mTc-DTPA renal scintigraphy and histopathological study. 99mTc-DTPA renal study was performed to detect and quantify signs of obstruction and to evaluate renal function. Statistical analysis was performed through the Student t-test with a significance level of P<0.05. Results. Nine of the ten rabbits presented left renal unit obstruction and one nonobstructive on the 99mTc-DTPA and histopathological studies. All the right renal units, which were not submitted to surgical procedure, were nonobstructed by the studies. There was a general agreement between scintigraphy and histopathological results in both groups. Conclusion. The experimental model promoted the creation of ureteral obstruction in rabbits, confirmed by nuclear medicine scintigraphy and histopathology, and could be used in further studies to better understand urinary obstruction. PMID:24489538

  4. The Effect of Irreversible Electroporation on the Femur: Experimental Study in a Rabbit Model.

    PubMed

    Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    Irreversible electroporation (IRE) is a novel ablation method that has been tested in humans with lung, prostate, kidney, liver, lymph node and presacral cancers. As a new non-thermal treatment, the use of IRE to ablate tumors in the musculoskeletal system might reduce the incidence of fractures. We aimed to determine the ablation threshold of cortical bone and to evaluate the medium- and long-term healing process and mechanical properties of the femur in a rabbit model post-IRE ablation. The ablation threshold of cortical bone was between 1090 V/cm and 1310 V/cm (120 pulses). IRE-ablated femurs displayed no detectable fracture but did exhibit signs of recovery, including osteoblast regeneration, angiogenesis and bone remodeling. In the ablation area, revascularization appeared at 4 weeks post-IRE. Osteogenic activity peaked 8 weeks post-IRE and remained high at 12 weeks. The mechanical strength decreased briefly 4 weeks post-IRE but returned to normal levels within 8 weeks. Our experiment revealed that IRE ablation preserved the structural integrity of the bone cortex, and the ablated bone was able to regenerate rapidly. IRE may hold unique promise for in situ bone tissue ablation because rapid revascularization and active osteogenesis in the IRE ablation area are possible. PMID:26655843

  5. Comparison of ultrasonic suture welding and traditional knot tying in a rabbit rotator cuff repair model.

    PubMed

    Nho, Shane J; Cole, Brian J; Mazzocca, Augustus D; Williams, James M; Romeo, Anthony A; Bush-Joseph, Charles A; Bach, Bernard R; Hallab, Nadim J

    2006-01-01

    The purpose of this study is to evaluate ultrasonic suture welding of monofilament suture in an animal model of rotator cuff repair with biomechanical and histologic analyses. We randomly assigned 46 shoulders in 23 rabbits to 1 of 3 treatment groups: sham-operated (n = 15), knotted (n = 15), and welded (n = 16). Supraspinatus defects were surgically created and acutely repaired with suture anchors loaded with either No. 2-0 Ethibond for knotted group or No. 2-0 nylon for welded shoulders. Eighteen weeks postoperatively, all animals were killed, and the shoulders underwent either biomechanical testing or histologic analysis. The maximum stress of the sham-operated group (20.6 N/mm2) was significantly greater than that of both the knotted (10.2 N/mm2) and welded (8.3 N/mm2) groups (P < .05), but no differences were observed between the knotted and welded groups. Although some histologic changes were noted, none was considered to be significant to distinguish either group. PMID:16979062

  6. Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation.

    PubMed

    Yamamoto, K; Yoshimine, T; Yanagihara, T

    1985-12-01

    Regional cerebral ischemia was produced in the rabbit by unilateral transorbital occlusion of the middle cerebral artery (procedure I); the middle cerebral and azygos anterior cerebral or anterior communicating artery (procedure II); or the middle cerebral, azygos anterior cerebral or anterior communicating, and internal carotid artery (procedure III). Evolution of ischemic lesions was examined with the immunohistochemical reaction for tubulin. With procedure I, ischemic lesions did not become constantly visible for 6 h in the basal ganglia and for 8 h in the frontoparietal region of the cerebral cortex. With procedure II, it was shortened to 3 h in the basal ganglia and to 6 h in the cerebral cortex. With procedure III, the ischemic lesions were observed in 1 h both in the basal ganglia and in the cerebral cortex as loss of the reaction for tubulin in the neuropil, nerve cell bodies, and dendrites. The evidence of neuronal damage became apparent in the same areas later by staining with hematoxylin-eosin. The experimental model presented here may be suitable for investigation of the mechanism that shifts reversible ischemia to cerebral infarction and for evaluation of the effectiveness of pharmacological intervention. PMID:3932374

  7. [Morphologic study of the intestine in an experimental model of amnioinfusion in fetal rabbits with gastroschisis].

    PubMed

    Muñoz, M E; Albert, A; Juliá, V; Sancho, M A; Grande, C; Martínez, A; Morales, L

    2002-10-01

    An experimental model of serial amnioinfusion has been developed in fetal rabbits with gastroschisis, using an intraamniotic catheter connected to a subcutaneous port. Fetuses of 4 groups were compared 7 days after surgery: group A: gastroschisis and daily amnioinfusion through an implanted catheter; group C: gastroschisis and blind amniotic catheter; group G: gastroschisis without catheter; group O: nonoperated fetuses. Survival rate, fetal body weight, lung weight, intestinal weight and length were determined. Computer aided morphometric analysis was performed, in which intestinal diameter, thickness and villi length were measured. Amniotic fluid samples were recovered along the experimental period. Intestinal length was significantly shorter and had a significantly thicker wall than nonoperated fetuses; we found no other morphometric differences between gastroschisis treated with amnioinfusion (group A) and the other gastroschisis groups (C and G). Amnioinfusion did not affect fetal survival rate; the amniotic catheter alone did not cause pulmonary hypoplasia due to significant amniotic leak. The physiological decrease in amniotic volume towards the end of gestation has not been modified by this regime of amnioinfusion. PMID:12601972

  8. Biologic response to orthopedic sutures: a histologic study in a rabbit model.

    PubMed

    Carr, Brian J; Ochoa, Leah; Rankin, David; Owens, Brett D

    2009-11-01

    Biologic reactivity to suture materials can have an effect on patient outcomes. The goal of this study was to determine the histologic response to 8 commonly used orthopedic sutures--Ethibond (Ethicon, Somerville, New Jersey), Ticron (Tyco, Waltham, Massachusetts), HiFi (Linvatec, Largo, Florida), Ultrabraid (Smith & Nephew, Memphis, Tennessee), MaxBraid (Biomet, Warsaw, Indiana), Orthocord (Mitek, Raynham, Massachusetts), MagnumWire (Opus Medical, San Juan Capistrano, California), and FiberWire (Arthrex, Naples, Florida)--using a rabbit model. The suture granuloms were evaluated at 30, 60, and 120 days with measurement of the fibrous capsule, the number of giant cells in and near the capsule, and the overall inflammatory grade: 1 (mild), 2 (moderate), and 3 (severe). MagnumWire and Ticron sutures initiated a more intense inflammatory reaction when compared to the other sutures. By 120 days, MagnumWire (P=.0297) and Ticron (P=.1855) had fewer giant cells at the soft tissue-suture interface, fewer giant cells within the capsule (P=.0074 and P=.0377, respectively), and the greatest capsular thickness of all suture types (P<.0001 and P=.1378, respectively). Differences exist between the biologic reactivity of commonly used orthopedic sutures that may be attributable to their material composition and/or braid characteristics. In comparison to other high-strength sutures, MagnumWire and Ticron stimulated a more intense foreign body inflammatory response. PMID:19902886

  9. Histopathological effects of intranasal phototherapy and nasal corticosteroids in allergic rhinitis in a rabbit model.

    PubMed

    Yurttas, Veysel; Şereflican, Murat; Erkoçoğlu, Mustafa; Terzi, Elçin Hakan; Kükner, Aysel; Oral, Mesut

    2015-08-01

    Allergic rhinitis is one of the most common health problems and has a major effect on quality of life. Although new-generation antihistamines and nasal steroids are the main treatment options, complete resolution cannot be obtained in some patients. Besides common side effects such as nasal irritation and epistaxis, the use of these drugs is controversial in some patients, such as pregnant or breastfeeding women. These findings highlight the need for new treatment options. Although phototherapy has been successfully used in the treatment of atopic dermatitis, which is an IgE-mediated disease and shares several common pathogenic features with allergic rhinitis, there are limited studies about its role in the treatment of allergic rhinitis. In this study, we aimed to evaluate and compare the histopathological effects of intranasal phototherapy (Rhinolight) and nasal corticosteroid treatment on the nasal mucosa in allergic rhinitis in a rabbit model and we found that both treatment options significantly reduced inflammation in the nasal mucosa without increasing apoptosis of mucosal cells. PMID:26123190

  10. The Effect of Irreversible Electroporation on the Femur: Experimental Study in a Rabbit Model

    PubMed Central

    Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    Irreversible electroporation (IRE) is a novel ablation method that has been tested in humans with lung, prostate, kidney, liver, lymph node and presacral cancers. As a new non-thermal treatment, the use of IRE to ablate tumors in the musculoskeletal system might reduce the incidence of fractures. We aimed to determine the ablation threshold of cortical bone and to evaluate the medium- and long-term healing process and mechanical properties of the femur in a rabbit model post-IRE ablation. The ablation threshold of cortical bone was between 1090 V/cm and 1310 V/cm (120 pulses). IRE-ablated femurs displayed no detectable fracture but did exhibit signs of recovery, including osteoblast regeneration, angiogenesis and bone remodeling. In the ablation area, revascularization appeared at 4 weeks post-IRE. Osteogenic activity peaked 8 weeks post-IRE and remained high at 12 weeks. The mechanical strength decreased briefly 4 weeks post-IRE but returned to normal levels within 8 weeks. Our experiment revealed that IRE ablation preserved the structural integrity of the bone cortex, and the ablated bone was able to regenerate rapidly. IRE may hold unique promise for in situ bone tissue ablation because rapid revascularization and active osteogenesis in the IRE ablation area are possible. PMID:26655843