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Sample records for rabbit elastase-induced model

  1. Morphology of elastase-induced cerebral aneurysm model in rabbit and rapid prototyping of elastomeric transparent replicas.

    PubMed

    Seong, Jaehoon; Sadasivan, Chander; Onizuka, Masanari; Gounis, Matthew J; Christian, Fletcher; Miskolczi, Laszlo; Wakhloo, Ajay K; Lieber, Baruch B

    2005-01-01

    In this work, we describe a methodology to fabricate transparent elastomeric vascular replicas using rapid prototyping techniques. First, the three-dimensional morphology of an elastase-induced aneurysm model in rabbit is acquired. The morphology is reconstructed from in vivo rotational angiography and it is compared with three-dimensional reconstructions obtained by computerized tomography and magnetic resonance imaging of an intraluminal arterial cast that was obtained from the same animal at sacrifice. Results show that resolution of the imaging modality strongly influences the level of detail, such as small side branches, in the final reconstruction. We developed an average morphology model for elastase-induced aneurysms in rabbits including the surrounding vasculature and describe a method for rapid prototyping of vascular models from the three-dimensional morphology. Our replicas can be manufactured in a short period of time and the final product is optically clear. In addition, the elasticity of the models can be controlled to represent arterial elasticity, which makes them ideal for optical investigations of detailed flow dynamics using measurement tools such as particle image velocimetry.

  2. 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.

  3. A Modified Method for Creating Elastase-Induced Aneurysms by Ligation of Common Carotid Arteries in Rabbits and Its Effect on Surrounding Arteries

    PubMed Central

    Kainth, Daraspreet; Salazar, Pascal; Safinia, Cyrus; Chow, Ricky; Bachour, Ornina; Andalib, Sasan; McKinney, Alexander M.; Divani, Afshin A.

    2017-01-01

    Background and Purpose Rabbit models of intracranial aneurysms are frequently used in pre-clinical settings. This study aimed to demonstrate an alternative, extravascular method for creating elastase-induced aneurysms, and how ligation of the right common carotid arteries (RCCA) can impact flow redistribution into left CCA (LCCA). Methods Elastase-induced aneurysms in 18 New Zealand rabbits (4.14 ± 0.314 kg) were created by applying 3–5 U of concentrated elastase solution to the exterior of the right and left CCA roots (RCCA and LCCA). After the induction of the aneurysm, the aneurysm was either kept intact to the rest of the corresponding CCA, severed from the rest of the CCA to allow for a free standing aneurysm, or was anchored to nearby tissue to influence the angle and orientation of the aneurysm with respect to the parent vessel. Ultrasound studies were performed before and after creation of aneurysms to collect blood flow measurements inside the aneurysm pouch and surrounding arteries. Prior to sacrificing the animals, computed tomography angiography studies were performed. Harvested aneurysmal tissues were used for histological analysis. Results Elastase-induced aneurysms were successfully created by the extravascular approach. Histological studies showed that the biological response was similar to human cerebral aneurysms and previously published elastase-induced rabbit aneurysm models. Ultrasound measurements indicated that after the RCCA was ligated, blood flow significantly increased in the LCCA at one-month follow-up. Conclusion An alternate method for creating elastase-induced aneurysms has been demonstrated. The novel aspects of our method allow for ligation of one or both common carotid arteries to create a single or bilateral aneurysm with an ability to control the orientation of the induced aneurysm. PMID:28243348

  4. 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

  5. Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.

    PubMed

    Baila, Bulin; Ohno, Yasushi; Nagamoto, Hisashi; Kotosai, Kounori; Yabuuchi, Youichi; Funaguchi, Norihiko; Ito, Fumitaka; Endo, Junki; Mori, Hidenori; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Minatoguchi, Shinya

    2012-01-01

    Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

  6. Structure-function relations in an elastase-induced mouse model of emphysema.

    PubMed

    Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Majumdar, Arnab; Lutchen, Kenneth R; Suki, Béla

    2011-09-01

    Emphysema is a progressive disease characterized by the destruction of peripheral airspaces and subsequent decline in lung function. However, the relation between structure and function during disease progression is not well understood. The objective of this study was to assess the time course of the structural, mechanical, and remodeling properties of the lung in mice after elastolytic injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase, respiratory impedance, the constituents of lung extracellular matrix, and histological sections of the lung were evaluated. In the control group, no changes were observed in the structural or functional properties, whereas, in the treatment group, the respiratory compliance and its variability significantly increased by Day 21 (P < 0.001), and the difference in parameters decreased with increasing positive end-expiratory pressure. The heterogeneity of airspace structure gradually increased over time. Conversely, the relative amounts of elastin and type I collagen exhibited a peak (P < 0.01) at Day 2, but returned to baseline levels by Day 21. Structure-function relations manifested themselves in strong correlations between compliance parameters and both mean size and heterogeneity of airspace structure (r(2) > 0.9). Similar relations were also obtained in a network model of the parenchyma in which destruction was based on the notion that mechanical forces contribute to alveolar wall rupture. We conclude that, in a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local, mechanical, force-induced failure of remodeled collagen.

  7. 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.

  8. 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.

  9. Elastase-Induced Parenchymal Disruption and Airway Hyper Responsiveness in Mouse Precision Cut Lung Slices: Toward an Ex vivo COPD Model

    PubMed Central

    Van Dijk, Eline M.; Culha, Sule; Menzen, Mark H.; Bidan, Cécile M.; Gosens, Reinoud

    2017-01-01

    Background: COPD is a progressive lung disease characterized by emphysema and enhanced bronchoconstriction. Current treatments focused on bronchodilation can delay disease progression to some extent, but recovery or normalization of loss of lung function is impossible. Therefore, novel therapeutic targets are needed. The importance of the parenchyma in airway narrowing is increasingly recognized. In COPD, the parenchyma and extracellular matrix are altered, possibly affecting airway mechanics and enhancing bronchoconstriction. Our aim was to set up a comprehensive ex vivo Precision Cut Lung Slice (PCLS) model with a pathophysiology resembling that of COPD and integrate multiple readouts in order to study the relationship between parenchyma, airway functionality, and lung repair processes. Methods: Lungs of C57Bl/6J mice were sliced and treated ex vivo with elastase (2.5 μg/ml) or H2O2 (200 μM) for 16 h. Following treatment, parenchymal structure, airway narrowing, and gene expression levels of alveolar Type I and II cell repair were assessed. Results: Following elastase, but not H2O2 treatment, slices showed a significant increase in mean linear intercept (Lmi), reflective of emphysema. Only elastase-treated slices showed disorganization of elastin and collagen fibers. In addition, elastase treatment lowered both alveolar Type I and II marker expression, whereas H2O2 stimulation lowered alveolar Type I marker expression only. Furthermore, elastase-treated slices showed enhanced methacholine-induced airway narrowing as reflected by increased pEC50 (5.87 at basal vs. 6.50 after elastase treatment) and Emax values (47.96 vs. 67.30%), and impaired chloroquine-induced airway opening. The increase in pEC50 correlated with an increase in mean Lmi. Conclusion: Using this model, we show that structural disruption of elastin fibers leads to impaired alveolar repair, disruption of the parenchymal compartment, and altered airway biomechanics, enhancing airway contraction

  10. Elastase induces lung epithelial cell autophagy through placental growth factor

    PubMed Central

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD. PMID:24988221

  11. Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

    PubMed Central

    Kim, Dong Kwan; Zhu, Jianliang; Kozyak, Benjamin W; Burkman, James M; Rubinstein, Neal A; Lankford, Edward B; Stedman, Hansell H; Nguyen, Taitan; Levine, Sanford; Shrager, Joseph B

    2003-01-01

    Background Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. Methods We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. Results In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. Conclusion This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans. PMID:12617755

  12. 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

  13. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

    PubMed

    Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2013-04-01

    Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p < 0.05) were observed among the groups treated with BMMC and evaluated after 7, 14 and 21 days. Analysis of the mean linear intercept (Lm) values for the different groups allowed to observe that the group treated with BMMC and evaluated after 21 days showed the most significant result. The group that received no treatment showed a statistically significant difference when compared to other groups, except the group treated and evaluated after 21 days, evidencing the efficacy of cell therapy with BMMC in pulmonary emphysema.

  14. From bench to bedside: utility of the rabbit elastase aneurysm model in preclinical studies of intracranial aneurysm treatment.

    PubMed

    Brinjikji, Waleed; Ding, Yong H; Kallmes, David F; Kadirvel, Ramanathan

    2016-05-01

    Preclinical studies are important in helping practitioners and device developers improve techniques and tools for endovascular treatment of intracranial aneurysms. Thus an understanding of the major animal models used in such studies is important. The New Zealand rabbit elastase induced arterial aneurysm of the common carotid artery is one of the most commonly used models in testing the safety and efficacy of new endovascular devices. In this review we discuss: (1) the various techniques used to create the aneurysm, (2) complications of aneurysm creation, (3) natural history of the arterial aneurysm, (4) histopathologic and hemodynamic features of the aneurysm, (5) devices tested using this model, and (6) weaknesses of the model. We demonstrate how preclinical studies using this model are applied in the treatment of intracranial aneurysms in humans. The model has similar hemodynamic, morphological, and histologic characteristics to human aneurysms, and demonstrates similar healing responses to coiling as human aneurysms. Despite these strengths, however, the model does have many weaknesses, including the fact that the model does not emulate the complex inflammatory processes affecting growing and ruptured aneurysms. Furthermore, the extracranial location of the model affects its ability to be used in preclinical safety assessments of new devices. We conclude that the rabbit elastase model has characteristics that make it a simple and effective model for preclinical studies on the endovascular treatment of intracranial aneurysms, but further work is needed to develop aneurysm models that simulate the histopathologic and morphologic characteristics of growing and ruptured aneurysms.

  15. 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.

  16. Elastase induces lung epithelial cell autophagy through placental growth factor: a new insight of emphysema pathogenesis.

    PubMed

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-09-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD.

  17. Role of LTB₄ in the pathogenesis of elastase-induced murine pulmonary emphysema.

    PubMed

    Shim, Y Michael; Paige, Mikell; Hanna, Halim; Kim, Su H; Burdick, Marie D; Strieter, Robert M

    2010-12-01

    Exaggerated levels of the leukotriene B₄ (LTB₄) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB₄ pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB₄ were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB₄ in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA₄ hydrolase-/- mice (LTB₄ deficient, LTA₄H-/-) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB₄ in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA₄H-/- mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH₂O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA₄H-/- mice were found to have significantly delayed influx of the CD45(high)CD11b(high)Ly6G(high) leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA₄H-/- mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB₄ played an important

  18. Experimental rabbit models of Chlamydia pneumoniae infection.

    PubMed Central

    Moazed, T. C.; Kuo, C.; Patton, D. L.; Grayston, J. T.; Campbell, L. A.

    1996-01-01

    Chlamydia pneumoniae (TWAR), a common cause of acute respiratory disease in humans, has recently been associated with coronary and aortic atherosclerosis. In this study, we evaluated rabbit models of chlamydial infection to investigate the pathogenesis of C. pneumoniae infection. New Zealand White rabbits were inoculated intranasally and intratracheally with C. pneumoniae, strain AR-39, and primary and repeated infection were assessed. After a single inoculation, lung pathology was characterized by a moderate self-resolving interstitial pneumonia with bronchiolitis of 21 days in duration. Chlamydial DNA was detected by polymerase chain reaction (PCR) intermittently in the upper respiratory tract and lung tissue through day 21 postinoculation, spleen tissue at day 14, and peripheral blood mononuclear cells at days 3 and 21. After repeated inoculations, chlamydial DNA was detected by PCR in the upper respiratory tract and lung tissue through day 42. Lung lesions consisted of multifocal interstitial mononuclear cell aggregates that persisted up to day 42. Watanabe heritable hyperlipidemic rabbits were less susceptible to C. pneumoniae infection. After multiple inoculations of Watanabe rabbits, C. pneumoniae was detected by PCR and/or immunocytochemistry until day 21. In conclusion, C. pneumoniae induced a moderate respiratory infection in these rabbit models. Images Figure 1 Figure 2 Figure 3 PMID:8579129

  19. 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.

  20. 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.

  1. Insulin modulates inflammatory and repair responses to elastase-induced emphysema in diabetic rats.

    PubMed

    Di Petta, Antonio; Greco, Karin V; Castro, Eveline O; Lopes, Fernanda D T Q S; Martins, Milton A; Capelozzi, Vera L; Moreira, Luiz F P; Sannomiya, Paulina

    2011-12-01

    As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.

  2. Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

    PubMed Central

    Supinski, Gerald S.; Kelsen, Steven G.

    1982-01-01

    The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length resulting from chronic hyperinflation of the thorax, while diaphragmatic muscle hypertrophy represents a response to changes in respiratory load and/or diaphragm configuration (La

  3. Three Variations in Rabbit Angiographic Stroke Models

    PubMed Central

    Culp, William C.; Woods, Sean D.; Brown, Aliza T.; Lowery, John D.; Hennings, Leah J.; Skinner, Robert D.; Borrelli, Michael J.; Roberson, Paula K.

    2012-01-01

    Purpose To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. Materials and Methods New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3–6 h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700–900 μm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24 hours after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). Results Infarct volume percent at 24 hours after stroke was lower for rabbits embolized with fresh clot (0.45% ± 0.14%), compared with aged clot (3.52% ± 1.31%) and insoluble microspheres (3.39% ± 1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). Conclusion The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs. PMID:23142182

  4. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats

    PubMed Central

    2012-01-01

    Background Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. Methods On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry. Results TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema. Conclusions TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages. PMID:22849372

  5. 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.

  6. 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

  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. Coactivator-Associated Arginine Methyltransferase-1 Function in Alveolar Epithelial Senescence and Elastase-Induced Emphysema Susceptibility.

    PubMed

    Sarker, Rim S J; John-Schuster, Gerrit; Bohla, Alexander; Mutze, Kathrin; Burgstaller, Gerald; Bedford, Mark T; Königshoff, Melanie; Eickelberg, Oliver; Yildirim, Ali Ö

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases worldwide. A major feature of COPD is emphysema, which is the progressive loss of alveolar tissue. Coactivator-associated arginine methyltransferase-1 (CARM1) regulates histone methylation and the transcription of genes involved in senescence, proliferation, and differentiation. Complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type II (ATII) cells. We thus hypothesized that CARM1 regulates the development and progression of emphysema. To address this, we investigated the contribution of CARM1 to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and small interfering (si)RNA-mediated knockdown in ATII-like LA4 cells in vitro. We demonstrate that emphysema progression in vivo is associated with a time-dependent down-regulation of CARM1. Importantly, elastase-treated CARM1 haploinsufficient mice show significantly increased airspace enlargement (52.5 ± 9.6 μm versus 38.8 ± 5.5 μm; P < 0.01) and lung compliance (2.8 ± 0.32 μl/cm H2O versus 2.4 ± 0.4 μl/cm H2O; P < 0.04) compared with controls. The knockdown of CARM1 in LA4 cells led to decreased sirtuin 1 expression (0.034 ± 0.003 versus 0.022 ± 0.001; P < 0.05) but increased expression of p16 (0.27 ± 0.013 versus 0.31 ± 0.010; P < 0.5) and p21 (0.81 ± 0.088 versus 1.28 ± 0.063; P < 0.01) and higher β-galactosidase-positive senescent cells (50.57 ± 7.36% versus 2.21 ± 0.34%; P < 0.001) compared with scrambled siRNA. We further demonstrated that CARM1 haploinsufficiency impairs transdifferentiation and wound healing (32.18 ± 0.9512% versus 8.769 ± 1.967%; P < 0.001) of alveolar epithelial cells. Overall, these results reveal a novel function of CARM1 in regulating emphysema development

  9. 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.

  10. 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

    2015-03-10

    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.

  11. Mathematical Modeling in a Feast of Rabbits.

    ERIC Educational Resources Information Center

    Jones, Graham A.

    1993-01-01

    Solves the problem of the reproduction of rabbit pairs utilizing the Fibonacci sequence. Examines modified versions of the problem, and presents a vignette of one modification based on the author's experience in using the approach with preservice middle school teachers. Extends the approach to other related problems. (MDH)

  12. 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

  13. Deterministic models of inhalational anthrax in New Zealand white rabbits.

    PubMed

    Gutting, Bradford

    2014-01-01

    Computational models describing bacterial kinetics were developed for inhalational anthrax in New Zealand white (NZW) rabbits following inhalation of Ames strain B. anthracis. The data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. Initial bacterial numbers were deposited spore dose. The first model was a single exponential ordinary differential equation (ODE) with 3 rate parameters that described mucociliated (physical) clearance, immune clearance (bacterial killing), and bacterial growth. At 36 hours postexposure, the ODE model predicted 1.7×10⁷ bacteria in the rabbit, which agreed well with data from actual experiments (4.0×10⁷ bacteria at 36 hours). Next, building on the single ODE model, a physiological-based biokinetic (PBBK) compartmentalized model was developed in which 1 physiological compartment was the lumen of the airways and the other was the rabbit body (lung tissue, lymph nodes, blood). The 2 compartments were connected with a parameter describing transport of bacteria from the airways into the body. The PBBK model predicted 4.9×10⁷ bacteria in the body at 36 hours, and by 45 hours the model showed all clearance mechanisms were saturated, suggesting the rabbit would quickly succumb to the infection. As with the ODE model, the PBBK model results agreed well with laboratory observations. These data are discussed along with the need for and potential application of the models in risk assessment, drug development, and as a general aid to the experimentalist studying inhalational anthrax.

  14. Annexin V decreases PS-mediated macrophage efferocytosis and deteriorates elastase-induced pulmonary emphysema in mice.

    PubMed

    Yoshida, S; Minematsu, N; Chubachi, S; Nakamura, H; Miyazaki, M; Tsuduki, K; Takahashi, S; Miyasho, T; Iwabuchi, T; Takamiya, R; Tateno, H; Mouded, M; Shapiro, S D; Asano, K; Betsuyaku, T

    2012-11-15

    Efferocytosis is believed to be a key regulator for lung inflammation in chronic obstructive pulmonary disease. In this study we pharmacologically inhibited efferocytosis with annexin V and attempted to determine its impact on the progression of pulmonary emphysema in mouse. We first demonstrated in vitro and in vivo efferocytosis experiments using annexin V, an inhibitor for phosphatidylserine-mediated efferocytosis. We then inhibited efferocytosis in porcine pancreatic elastase (PPE)-treated mice. PPE-treated mice were instilled annexin V intranasally starting from day 8 until day 20. Mean linear intercept (Lm) was measured, and cell apoptosis was assessed in lung specimen obtained on day 21. Cell profile, apoptosis, and mRNA expression of matrix metalloproteinases (MMPs) and growth factors were evaluated in bronchoalveolar lavage (BAL) cells on day 15. Annexin V attenuated macrophage efferocytosis both in vitro and in vivo. PPE-treated mice had a significant higher Lm, and annexin V further increased that by 32%. More number of macrophages was found in BAL fluid in this group. Interestingly, cell apoptosis was not increased by annexin V treatment both in lung specimens and BAL fluid, but macrophages from mice treated with both PPE and annexin V expressed higher MMP-2 mRNA levels and had a trend for higher MMP-12 mRNA expression. mRNA expression of keratinocyte growth factor tended to be downregulated. We showed that inhibited efferocytosis with annexin V worsened elastase-induced pulmonary emphysema in mice, which was, at least partly, attributed to a lack of phenotypic change in macrophages toward anti-inflammatory one.

  15. A Rabbit Model of Inhalation Injury,

    DTIC Science & Technology

    1993-03-01

    5, 6, 7, 8, 9,10,11,12. Group I ( B ) One unit of smoke without breath hold One animal died 26 hours after 25 units of smoke exposure Smoke (5seconds...concentrations in r- b - Air (I2•~o..$) 1. 2, 3, 4, 5, 6, 7. 8, 9.10,11,12. bits receiving 8 units without BH and 25 units wvith BH were Figure 1. The...most commonly used in- 0 0 1 3 4 travenous anesthetic agent for rabbits, and has the seri- Day& ous disadvantage of depressing respiration; this is the

  16. Creating a Long-Term Diabetic Rabbit Model

    PubMed Central

    Wang, Jianpu; Wan, Rong; Mo, Yiqun; Zhang, Qunwei; Sherwood, Leslie C.; Chien, Sufan

    2010-01-01

    This study was to create a long-term rabbit model of diabetes mellitus for medical studies of up to one year or longer and to evaluate the effects of chronic hyperglycemia on damage of major organs. A single dose of alloxan monohydrate (100 mg/kg) was given intravenously to 20 young New Zealand White rabbits. Another 12 age-matched normal rabbits were used as controls. Hyperglycemia developed within 48 hours after treatment with alloxan. Insulin was given daily after diabetes developed. All animals gained some body weight, but the gain was much less than the age-matched nondiabetic rabbits. Hyperlipidemia, higher blood urea nitrogen and creatinine were found in the diabetic animals. Histologically, the pancreas showed marked beta cell damage. The kidneys showed significantly thickened afferent glomerular arterioles with narrowed lumens along with glomerular atrophy. Lipid accumulation in the cytoplasm of hepatocytes appeared as vacuoles. Full-thickness skin wound healing was delayed. In summary, with careful management, alloxan-induced diabetic rabbits can be maintained for one year or longer in reasonably good health for diabetic studies. PMID:21234414

  17. 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

  18. 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.

  19. Comprehensive analysis of elastase-induced pulmonary emphysema in mice: effects of ambient existing particulate matters.

    PubMed

    Inoue, Ken-ichiro; Koike, Eiko; Takano, Hirohisa

    2010-11-01

    Pulmonary exposure of rodents to porcine pancreatic elastase (PPE) induces lesions that morphologically resemble human panacinar emphysema. However, there has been little work on the comprehensive analysis of this model. The present study was designed to extensively examine the biological effects of PPE on inflammation, cell damage, emphysematous change, and cholinergic reactivity in the lungs of mice. Furthermore, we evaluated the effects of pulmonary exposure to diesel exhaust particles (DEP) on the disease model. Intratracheal administration of PPE induced (1) proinflammatory response in the lungs that was characterized by significant infiltration of leukocytes such as macrophages, eosinophils, and lymphocytes and an increased level of interleukin-1β in lung homogenates, (2) lung cell damage, indicated by higher levels of total protein, lactate dehydrogenase, and alkaline phosphatase in lung homogenates, (3) emphysema-related morphological changes including airspace enlargement and progressive destruction of alveolar wall structures, and (4) airway responsiveness to methacholine in the context of the compliance value of the respiratory system in a dose-dependent manner showing an overall trend. A single intratracheal administration of DEP did not significantly facilitate the hallmark of the disease. This is the first study to extensively analyze PPE-induced lung emphysema in mice with evaluation of the effects of DEP. Furthermore, this bioassay may be applied to future investigations that evaluate new therapeutic agents or risk factors for pulmonary emphysema.

  20. Subject-Specific Computational Modeling of Evoked Rabbit Phonation

    PubMed Central

    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

  1. 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.

  2. 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.

  3. 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

    2016-01-01

    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.

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

    SciTech Connect

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

    2016-01-28

    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.

  5. An improved rabbit ear model for assessing comedogenic substances.

    PubMed

    Kligman, A M; Kwong, T

    1979-06-01

    A simplified comedogenic assay is described in which test materials are applied for 2 weeks to the ears of rabbits just external to the ear canal. Excised tissue is thus immersed in water at 60 degrees C for 2 min, yielding a sheet of epidermis with microcomedones attached. The magnitude of follicular hyperkeratosis is extracted with the stereomicroscope. Sixteen materials were evaluated by the new and old model which required histological sectioning. Agreement was excellent.

  6. A New Rabbit Model of Pediatric Traumatic Brain Injury

    PubMed Central

    Zhang, Zhi; Saraswati, Manda; Koehler, Raymond C.; Robertson, Courtney

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a common cause of disability in childhood, resulting in numerous physical, behavioral, and cognitive sequelae, which can influence development through the lifespan. The mechanisms by which TBI influences normal development and maturation remain largely unknown. Pediatric rodent models of TBI often do not demonstrate the spectrum of motor and cognitive deficits seen in patients. To address this problem, we developed a New Zealand white rabbit model of pediatric TBI that better mimics the neurological injury seen after TBI in children. On postnatal Day 5-7 (P5-7), rabbits were injured by a controlled cortical impact (6-mm impactor tip; 5.5 m/sec, 2-mm depth, 50-msec duration). Rabbits from the same litter served as naïve (no injury) and sham (craniotomy alone) controls. Functional abilities and activity levels were measured 1 and 5 d after injury. Maturation level was monitored daily. We performed cognitive tests during P14-24 and sacrificed the animals at 1, 3, 7, and 21 d after injury to evaluate lesion volume and microglia. TBI kits exhibited delayed achievement of normal developmental milestones. They also demonstrated significant cognitive deficits, with lower percentage of correct alternation rate in the T-maze (n=9-15/group; p<0.001) and less discrimination between novel and old objects (p<0.001). Lesion volume increased from 16% at Day 3 to 30% at Day 7 after injury, indicating ongoing secondary injury. Activated microglia were noted at the injury site and also in white matter regions of the ipsilateral and contralateral hemispheres. The neurologic and histologic changes in this model are comparable to those reported clinically. Thus, this rabbit model provides a novel platform for evaluating neuroprotective therapies in pediatric TBI. PMID:25758339

  7. [Chronic stress model in New Zealand white rabbit with hyperlipidemia].

    PubMed

    Yu, Z M; Wang, M; Chen, K; Xiao, L Y; Deng, X T; Gong, T

    2017-02-21

    Objective: To establish and evaluate chronic stress model in New Zealand white rabbit with hyperlipidemia. Methods: A total of 45 clearing grade male New Zealand white rabbits were divided into four groups with random number table method: control (CON), normal diet combined with chronic stress for 8 weeks (CON+ CS), high fat diet (HFD) and high fat diet for 4 weeks combined with chronic stress for 8 weeks (HFD+ CS). Both social stress and physical stress methods were adopted.One-way ANOVA was used for comparison among groups. Results: (1) Chronic stress model assessments: ①body weight, the weight gain of stress groups was significantly reduced; ②behavioral assessment, rabbits exposed to stress in CON+ CS and HFD+ CS group [54%±7%, 55%±5%] exhibited more inactivity behavior than CON and HFD group [27%±5.28%, 34%±6%, P<0.01, P<0.05]; ③serum indexes: after stress regime for 4 weeks, cortisol of HFD+ CS was higher than HFD group [(60±5) ng/ml vs (38±4) ng/ml, P=0.001]. After 8 weeks, the serum levels of hs-CRP and IL-6 also elevated. (2) The effect of hyperlipidemia on chronic stress: compared with CON+ CS, HFD+ CS group showed more inactivity behavior and rising levels of cortisol, hs-CRP and IL-6. (3) Blood lipids: chronic stress induced raised serum total cholesterol. Conclusions: (1)Chronic stress model in rabbit with hyperlipidemia could be successfully established with 4-week high lipid feed followed by social stress combined with physical stress for 8 weeks.(2) Hyperlipidemia and chronic stress influences each other.

  8. Modeling of the jack rabbit series of experiments with a temperature based reactive burn model

    NASA Astrophysics Data System (ADS)

    Desbiens, Nicolas

    2017-01-01

    The Jack Rabbit experiments, performed by Lawrence Livermore National Laboratory, focus on detonation wave corner turning and shock desensitization. Indeed, while important for safety or charge design, the behaviour of explosives in these regimes is poorly understood. In this paper, our temperature based reactive burn model is calibrated for LX-17 and compared to the Jack Rabbit data. It is shown that our model can reproduce the corner turning and shock desensitization behaviour of four out of the five experiments.

  9. Evaluation of mycobacterial virulence using rabbit skin liquefaction model.

    PubMed

    Zhang, Guoping; Zhu, Bingdong; Shi, Wanliang; Wang, Mingzhu; Da, Zejiao; Zhang, Ying

    2010-01-01

    Liquefaction is an important pathological process that can subsequently lead to cavitation where large numbers of bacilli can be coughed up which in turn causes spread of tuberculosis in humans. Current animal models to study the liquefaction process and to evaluate virulence of mycobacteria are tedious. In this study, we evaluated a rabbit skin model as a rapid model for liquefaction and virulence assessment using M. bovis BCG, M. tuberculosis avirulent strain H37Ra, M. smegmatis, and the H37Ra strains complemented with selected genes from virulent M. tuberculosis strain H37Rv. We found that with prime and/or boosting immunization, all of these live bacteria at enough high number could induce liquefaction, and the boosting induced stronger liquefaction and more severe lesions in shorter time compared with the prime injection. The skin lesions caused by high dose live BCG (5×10 (6) ) were the most severe followed by live M. tuberculosis H37Ra with M. smegmatis being the least pathogenic. It is of interest to note that none of the above heat-killed mycobacteria induced liquefaction. When H37Ra was complemented with certain wild type genes of H37Rv, some of the complemented H37Ra strains produced more severe skin lesions than H37Ra. These results suggest that the rabbit skin liquefaction model can be a more visual, convenient, rapid and useful model to evaluate virulence of different mycobacteria and to study the mechanisms of liquefaction.

  10. Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

    PubMed Central

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

    2009-01-01

    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

  11. Microglia activation in a pediatric rabbit model of tuberculous meningitis

    PubMed Central

    Tucker, Elizabeth W.; Pokkali, Supriya; Zhang, Zhi; DeMarco, Vincent P.; Klunk, Mariah; Smith, Elizabeth S.; Ordonez, Alvaro A.; Penet, Marie-France; Bhujwalla, Zaver; Kannan, Sujatha

    2016-01-01

    ABSTRACT Central nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes. The presence of meningitis and tuberculomas was demonstrated histologically and by in vivo magnetic resonance imaging (MRI). The extent of microglial activation was quantified by in vitro immunohistochemistry as well as non-invasive in vivo imaging of activated microglia/macrophages with positron emission tomography (PET). Subarachnoid infection induced characteristic leptomeningeal and perivascular inflammation and TB lesions with central necrosis, a cellular rim and numerous bacilli on pathologic examination. Meningeal and rim enhancement was visible on MRI. An intense microglial activation was noted in M. tuberculosis-infected animals in the white matter and around the TB lesions, as evidenced by a significant increase in uptake of the tracer 124I-DPA-713, which is specific for activated microglia/macrophages, and confirmed by quantification of Iba-1 immunohistochemistry. Neurobehavioral analyses demonstrated signs similar to those noted in children with delayed maturation and development of neurological deficits resulting in significantly worse composite behavior scores in M. tuberculosis-infected animals. We have established a rabbit model that mimics features of TB meningitis in young children. This model could provide a platform for evaluating novel therapies, including host-directed therapies, against TB meningitis relevant to a young child's developing brain. PMID:27935825

  12. Characterization of Raised Phonation in an Evoked Rabbit Phonation Model

    PubMed Central

    Swanson, Erik R.; Abdollahian, Davood; Ohno, Tsunehisa; Ge, Pingjiang; Zealear, David L.; Rousseau, Bernard

    2015-01-01

    Objectives/Hypothesis Our laboratory has developed an in vivo rabbit model to investigate the effects of phonation on expression and turnover of the vocal fold extracellular matrix. As a logical outgrowth of this research to include phonotrauma in the present study, we investigated the hypothesis that an increase in airflow rate delivered to the glottis produces a change in glottal configuration and an increase in mean phonation intensity. Study Design Prospective animal study. Methods Six New Zealand white breeder rabbits weighing 3 to 5 kg were used in this study. A rigid endoscope and camera were used to document glottal configuration. Acoustic signals of modal and raised phonation were recorded and digitized. Two separate one-way repeated measures analysis of variance (ANOVA) tests were used to investigate within subject differences in phonation intensity and fundamental frequency between modal and raised phonation. Results Phonation intensity was 54.19 dB SPL (6.21 standard deviations [SD]) during modal phonation, and 60.31 dB SPL (5.68 SD) during raised phonation. Endoscopic images revealed a convergent glottis, with greater separation of the vocal folds during raised phonation. Results of ANOVA revealed a significant within subjects effect for phonation intensity (P = .011). Pairwise comparisons revealed that phonation intensity increased significantly during raised phonation, compared to modal phonation (P = .008). No differences in mean fundamental frequency were observed between phonation conditions. Conclusions Improved understanding of factors that control phonation output in the in vivo rabbit model will result in improved capabilities to match phonation dose across animals and provide immediate direction to future biochemical studies. PMID:19422027

  13. New Zealand white rabbit as a nonsurgical experimental model for Salmonella enterica gastroenteritis.

    PubMed

    Hanes, D E; Robl, M G; Schneider, C M; Burr, D H

    2001-10-01

    Rabbits orally challenged with Salmonella enterica developed a dose-dependent diarrheal disease comparable to human salmonellosis. Viable Salmonella organisms recovered from the intestine and deep tissues indicate local and systemic infections. Therefore, results show that the rabbit can be used as a model for diarrheal disease and sequelae associated with salmonellosis.

  14. Modelling landscape-level numerical responses of predators to prey: the case of cats and rabbits.

    PubMed

    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

  15. 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.

  16. 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

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

    PubMed

    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.

  18. 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.

  19. An experimental model of ischemia in rabbit hindlimb.

    PubMed Central

    Hong, J. H.; Bahk, Y. W.; Suh, J. S.; Kwak, B. K.; Shim, H. J.; Kim, J. S.; Kim, H. S.; Moon, Y. H.; Kim, S. J.; Chung, J. W.; Park, J. H.

    2001-01-01

    This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia. PMID:11641535

  20. 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

  1. 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.

  2. Leukotriene B4 levels in rabbit maxillary sinusitis: limitations of the current model.

    PubMed

    Hurley, D B; Smith, G S; Vogler, G A; Desponde, Y; Citardi, M J

    2001-01-01

    Since the late 1980s, the rabbit model for sinusitis has been widely used for experimental studies on sinusitis; however, the clinical relevance of these experimental data has been questioned. To elucidate the role of leukotrienes in the pathogenesis of sinusitis, leukotriene B4 (LTB4) levels were determined in acute Streptococcus pneumoniae sinusitis in this model. The rabbit model for acute maxillary sinusitis was utilized. Briefly, the right maxillary ostium of each New Zealand white rabbit was occluded with cyanoacrylate under general anesthesia. Twenty-four hours after occlusion, the occluded sinus received an inoculation of 10(8) Streptococcus pneumoniae (ATCC 10813) or a sham inoculation of saline alone. Rabbits were then sacrificed one week later, and the maxillary sinus mucosae were harvested. Leukotriene B4 levels were determined by ELISA assay. LTB4 levels in the sinuses inoculated with bacteria tended to be higher; however, statistical analysis did not reveal significant differences between the experimental and control groups. It is possible to reliably assess leukotriene B4 levels in this model of sinusitis. Although the data suggest a trend for elevated LTB4 levels, statistical analysis did not support this conclusion. The study also demonstrated significant limitations in the current rabbit model for sinusitis; that is, the standard human sinus bacterial pathogens are minimally pathogenic in rabbit sinuses and the small size of the sinus limits the material available for assay. Further modifications of the model are necessary. After such adjustments, the role of leukotrienes in sinusitis may be further explored.

  3. An animal model of hypersensitivity pneumonitis in the rabbit.

    PubMed Central

    Moore, V L; Hensley, G T; Fink, J N

    1975-01-01

    This study was devised to produce an animal model of hypersensitivity pneumonitis in order to study both the induction and the elicitation of the disease. Rabbits exposed by aerosol to large quantities of pigeon antigens developed a humoral, but not cellular, immunologic response. Moreover, their lungs were essentially normal histologically. A single i.v. injection of killed BCG in oil permitted the induction of pulmonary cell-medid hypersensitivity to the inhaled antigen, as well as the development of pulmonary lesions which were more severe than that caused by the administration of BCG alone. The humoral immunologic response to the inhaled antigen was not increased after BCG injection. Since many individuals are exposed to the etiologic agents of hypersensitivity pneumonitis for extended periods without developing the disease, these findings in animals suggest that some event may occur to induce cell mediated hypersensitivity in order to initiate the disease process. In addition, we have shown that animals with normal lung histology and circulating complement-fixing antibodies undergo serum complement (CH50) depression after an aerosol challenge with the specific antigen. Animals with circulating, complement-fixing antibodies, and inflamed lungs (BCG-induced failed to undergo a complement depression subsequent to an aerosol challenge with specific antigens. These results re consistent with those seen in symptomatic and asymptomatic pigeon breeders and suggest that antigen distribution through the lung is important in the pathogenesis of hypersensitivity pneumonitis. Images PMID:1099122

  4. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

    PubMed

    Del Amo, Eva M; Urtti, Arto

    2015-08-01

    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

  5. Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

    PubMed Central

    Qin, Huamin; Janowski, Miroslaw; Pearl, Monica S.; Malysz-Cymborska, Izabela; Li, Shen; Eberhart, Charles G.

    2017-01-01

    The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery. PMID:28103265

  6. Investigations of a rabbit (Oryctolagus cuniculus) model of systemic lupus erythematosus (SLE), BAFF and its receptors.

    PubMed

    Yang, Jiahui; Pospisil, Richard; Ray, Satyajit; Milton, Jacqueline; Mage, Rose G

    2009-12-30

    B-cell activation factor belonging to the tumor necrosis factor family (BAFF) is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE). Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus) model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC) were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI) decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities of diseases

  7. Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model

    PubMed Central

    Lim, Kyung Seob; Bae, In Ho; Park, Jun-Kyu; Park, Dae Sung; Kim, Jong Min; Kim, Jung Ha; Cho, Dong Lyun; Sim, Doo Sun; Park, Keun-Ho; Hong, Young Joon; Ahn, Youngkeun

    2013-01-01

    Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7±0.18 mm2 in the AES group vs. 0.4±0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8±5.06% in the AES group vs. 10.5±6.80% in the PES group, p<0.05), and in the fibrin score (0.4±0.51 in the AES group vs. 2.7±0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model. PMID:24400214

  8. 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

  9. Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors.

    PubMed

    Xie, Jie; Jones, Thomas J; Feng, Dongni; Cook, Todd G; Jester, Andrea A; Yi, Ru; Jawed, Yameena T; Babbey, Clifford; March, Keith L; Murphy, Michael P

    2017-02-16

    Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28- T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28- (-28%), CD8+CD28- T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1-LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution

  10. Animal models of bronchopulmonary dysplasia. The preterm and term rabbit models.

    PubMed

    D'Angio, Carl T; Ryan, Rita M

    2014-12-15

    Bronchopulmonary dysplasia (BPD) is an important lung developmental pathophysiology that affects many premature infants each year. Newborn animal models employing both premature and term animals have been used over the years to study various components of BPD. This review describes some of the neonatal rabbit studies that have contributed to the understanding of BPD, including those using term newborn hyperoxia exposure models, premature hyperoxia models, and a term newborn hyperoxia model with recovery in moderate hyperoxia, all designed to emulate aspects of BPD in human infants. Some investigators perturbed these models to include exposure to neonatal infection/inflammation or postnatal malnutrition. The similarities to lung injury in human premature infants include an acute inflammatory response with the production of cytokines, chemokines, and growth factors that have been implicated in human disease, abnormal pulmonary function, disordered lung architecture, and alveolar simplification, development of fibrosis, and abnormal vascular growth factor expression. Neonatal rabbit models have the drawback of limited access to reagents as well as the lack of readily available transgenic models but, unlike smaller rodent models, are able to be manipulated easily and are significantly less expensive than larger animal models.

  11. A novel approach for the annulus needle puncture model of intervertebral disc degeneration in rabbits

    PubMed Central

    Lei, Tao; Zhang, Yuan; Zhou, Qiang; Luo, Xiaoji; Tang, Ke; Chen, Rongsheng; Yu, Chang; Quan, Zhengxue

    2017-01-01

    Objective: To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. Methods: Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longitudinal study to assess changes in disc height over time, serial X-rays, T2-weighted magnetic resonance imaging (MRI) (T2WI), and T2 mapping MRI were performed pre-operation and at 2, 4, and 6 weeks after puncture. Three rabbits were randomly selected for histological evaluation at 4 weeks post-operation. In addition, the remaining rabbits underwent a second surgery at 6 weeks after puncture. Results: All rabbits underwent the initial and second surgeries successfully without nerve-related complications. The operations had no significant effects on the rabbit body weight, and partial mild intra-abdominal adhesions were found in only 1 rabbit. The punctured discs were confirmed to be those of interest post-surgery and displayed progressive degeneration in disc height index (%), T2WI, and T2 relaxation time over time. At 4 weeks after puncture, a histological analysis revealed notochordal cell loss from the nucleus pulposus, fibrocartilage filling the nucleus pulposus space, and annulus fibrosus disorganization. Conclusion: The annular needle puncture model established through a transabdominal approach, which demonstrates better visualization, exact identification, consistent degeneration degrees and minimal complications, is radiologically and histologically consistent with human IVD degeneration. T2 mapping MRI can quantitatively discriminate between grades of mild degeneration. PMID:28386320

  12. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

    SciTech Connect

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

  13. Combination therapy with terbinafine and amphotericin B in a rabbit model of experimental invasive aspergillosis.

    PubMed

    Kirkpatrick, William R; Vallor, Ana C; McAtee, Robert K; Ryder, Neil S; Fothergill, Annette W; Rinaldi, Michael G; Patterson, Thomas F

    2005-11-01

    Antagonistic effects of combination therapy using amphotericin B (AmB) with agents which block ergosterol synthesis are a concern. Terbinafine was evaluated with AmB to assess antagonism or synergy in a rabbit model of invasive aspergillosis. Terbinafine had relatively little activity but did not demonstrate antagonism against AmB in our model.

  14. Development of an in vivo bone fatigue damage model using axial compression of the rabbit forelimb.

    PubMed

    Buettmann, Evan G; Silva, Matthew J

    2016-10-03

    Many nontraumatic fractures seen clinically in patients with metabolic bone disorders or on antiresorptive treatment show an increased incidence of microdamage accumulation and impaired intracortical remodeling. However, the lack of basal remodeling and Haversian bone in rodents limits their translatability in studying bone damage repair mechanisms. The work presented here demonstrates the development of the forelimb loading model in rabbits, the smallest mammal with intracortical Haversian remodeling. The forelimbs of post-mortem female New Zealand white rabbits were loaded in axial end compression to determine their basic monotonic and fatigue properties. Following time zero characterization, stress fractures were created in vivo and animals were allowed to recover for a period of two to five weeks. The rabbit forelimb when loaded in axial compression demonstrates a consistent mid-diaphyseal fracture location characterized by a local mixed compression-bending loading environment. Forelimb apparent stiffness, when fatigue loaded, demonstrates a progressive increase until macrocrack formation, at which time apparent stiffness rapidly declines until failure. Stress fractures in the rabbit ulna display robust periosteal expansion and woven bone formation two weeks following fracture. Subsequent healing at five weeks post-fracture is marked by woven bone densification, resorption and intracortical remodeling along the stress fracture line. The rabbit forelimb fatigue model is a promising new platform by which bone׳s response to damage may be studied.

  15. 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.

  16. 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

  17. Ex Vivo Electromechanical Reshaping of Costal Cartilage in the New Zealand White Rabbit Model

    PubMed Central

    Badran, Karam; Manuel, Cyrus; Waki, Curtis; Protsenko, Dmitry; Wong, Brian J. F.

    2014-01-01

    Objectives/Hypothesis Determine the effective electromechanical reshaping (EMR) parameters for shape change and cell viability in the ex vivo rabbit costal cartilage model. Study Design Ex vivo animal study combined with computer modeling to guide electrode placement and polarity selection. Methods Rabbit costal cartilages were secured in a jig that approximated the shape of the rabbit auricle framework. Finite element modeling was used to select the initial electrode geometry, polarity, spacing, and estimate dosimetry parameters. Porcine costal cartilage was utilized to refine the selection of dosing parameters. Parametric analysis was performed to determine the effect of voltage and application time on tissue shape change. Next, rabbit rib cartilage was reshaped, varying voltage and application time to identify the lowest parameters to produce acceptable shape change mimicking native auricular cartilage. Acceptable qualitative shape change was determined on a five-point Likert scale analyzed using one-way general linear analysis of variance. Confocal microscopy with live/dead cell viability analysis determined the degree of injury and the distribution of live and dead cells. Results The minimum acceptable deformation of rabbit costal cartilage was found at 4 V–3 minutes. Viability analysis of cartilage reshaped at 4 V–3 minutes demonstrates cell injury extending 2 mm away from each electrode with viable cells found between the electrodes. Conclusions The EMR parameters of 4 V–3 minutes demonstrates appropriate shape change producing grafts that resemble the native auricle and contains the viable cells adequate for clinical evaluation. The rabbit auricular reconstruction model using EMR is a feasible one. PMID:23553270

  18. 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.

  19. Protective effects of epigallocatechin-3 gallate on atrial electrical and structural remodeling in a rabbit rapid atrial pacing model.

    PubMed

    Zhu, Jifa; Zhang, Xiao; Li, Ling; Su, Gang

    2015-03-01

    Epigallocatechin-3 gallate (EGCG) is the major catechin in green tea. The aim of this study is to investigate the effects of EGCG on atrial electrical and structural remodeling in a rabbit rapid atrial pacing (RAP) model. New Zealand white rabbits were subjected to RAP with or without EGCG treatment. The atrial electrophysiology was studied. ELISA, Western blots, and RT-PCR were performed to determine the level of the inflammation markers, oxidative stress, and fibrogenic agents. Atrial tissue was stained with Masson's trichrome stain for fibrosis detection. RAP rabbits showed a significantly shorter atrial effective refractory period than control rabbits. Higher AF inducibility and longer AF duration were seen in the RAP group. AERP of rabbits received high dose EGCG were prolonged compared to RAP rabbits, and AF inducibility and duration of rabbits received high dose EGCG were lower. RAP rabbits have higher inflammation markers, higher oxidative stress, and more significant fibrosis within atrium, while high dose intervention of EGCG can lower the inflammation, oxidative stress, and fibrosis induced by RAP. Results showed that EGCG have protective effects on atrial electrical and structural remodeling in a rabbit RAP model in terms of attenuating of inflammation and oxidative stress.

  20. Rabbit maxillary sinus augmentation model with simultaneous implant placement: differential responses to the graft materials

    PubMed Central

    Kim, Young-Sung; Kim, Su-Hwan; Kim, Kyoung-Hwa; Jhin, Min-Ju; Kim, Won-Kyung; Lee, Young-Kyoo; Seol, Yang-Jo

    2012-01-01

    Purpose This study was performed to establish an experimental rabbit model for single-stage maxillary sinus augmentation with simultaneous implant placement. Methods Twelve mature New Zealand white rabbits were used for the experiments. The rabbit maxillary sinuses were divided into 3 groups according to sinus augmentation materials: blood clot (BC), autogenous bone (AB), and bovine-derived hydroxyapatite (BHA). Small titanium implants were simultaneously placed in the animals during the sinus augmentation procedure. The rabbits were sacrificed 4 and 8 weeks after surgery and were observed histologically. Histomorphometric analyses using image analysis software were also performed to evaluate the parameters related to bone regeneration and implant-bone integration. Results The BC group showed an evident collapse of the sinus membrane and limited new bone formation around the original sinus floor at 4 and 8 weeks. In the AB group, the sinus membrane was well retained above the implant apex, and new bone formation was significant at both examination periods. The BHA group also showed retention of the elevated sinus membrane above the screw apex and evident new bone formation at both points in time. The total area of the mineral component (TMA) in the area of interest and the bone-to-implant contact did not show any significant differences among all the groups. In the AB group, the TMA had significantly decreased from 4 to 8 weeks. Conclusions Within the limits of this study, the rabbit sinus model showed satisfactory results in the comparison of different grafting conditions in single-stage sinus floor elevation with simultaneous implant placement. We found that the rabbit model was useful for maxillary sinus augmentation with simultaneous implant placement. PMID:23346463

  1. 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.

  2. 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.

  3. 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

  4. [Effect of xuebijing oral effervescent tablet on endotoxin induced fever and disseminated intravascular coagulation rabbit model].

    PubMed

    Guo, Shan-Shan; Gao, Ying-Jie; Tian, Xue-Chuan; Jin, Ya-Hong; Liu, Fang-Zhou; Cui, Xiao-Lan

    2013-08-01

    In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.

  5. [The rabbit ear model as comedogenic test. 3. Histologic and enzyme histochemical studies of the follicle and sebaceous gland epithelium].

    PubMed

    Zimmermann, R

    1990-01-01

    A strongly comedogenic mineral oil induced histologically and enzyme-histochemically detectable changes in the follicles and sebaceous gland ducts in the skin of rabbit ears. These correlate to findings concerning acne vulgaris in humans. The rabbit ear model thus appears to be suitable for experimental studies into acne vulgaris.

  6. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    SciTech Connect

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

  7. A Rabbit Model of Acanthamoeba Keratitis That Better Reflects the Natural Human Infection.

    PubMed

    Feng, Xianmin; Zheng, Wenyu; Wang, Yuehua; Zhao, Donghai; Jiang, Xiaoming; Lv, Shijie

    2015-08-01

    Acanthamoeba species are ubiquitous, free-living protozoa that can invade the cornea and result in Acanthamoeba keratitis (AK), a painful progressive sight-threatening corneal disease. Disease progression in current animal models is too rapid to mimic AK in humans accurately. This study provides a novel method for establishing AK in rabbits and compared it with the conventional method with regard to pathogenesis and immune response in humans. The New Zealand white rabbits were randomly divided into two experimental groups (Groups A and B). Rabbits in the Group A (n = 14) received intrastromal injections of 1 × 10(4) /100 µL Acanthamoeba healyi trophozoites (conventional AK model). The Group B animals (n = 14) received microinjections of 1 × 10(4) /10 µL A. healyi trophozoites between the corneal epithelium and Bowman's layer, anterior to the corneal stroma (novel AK model). In addition, two rabbits were left untreated as normal controls. AK in the treated rabbits was evaluated clinically, histopathologically, and immunologically for 35 days. AK was successfully established in both the conventional and novel model groups. Compared with the Group A, AK in the Group B displayed an efficient immune response with less severe pathology. Moreover, the self-limiting but chronic nature of the infection in the Group B was strikingly similar to that of AK in humans. The novel animal model for AK described here more closely simulates the pathogenesis and immune response of Acanthamoeba corneal infection in humans than the animal models currently in use.

  8. 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

  9. Propionibacterium acnes and Staphylococcus lugdunensis cause pyogenic osteomyelitis in an intramedullary nail model in rabbits.

    PubMed

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

    2014-05-01

    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.

  10. Selective occlusion of lumbar arteries as a spinal cord ischemia model in rabbits.

    PubMed

    Maeda, Tomoyuki; Mori, Koichi; Shiraishi, Yoshimitsu; Tatebayashi, Kyoko; Kawai, Yasuaki

    2003-02-01

    Paraplegia is a devastating complication of operations requiring transient occlusion of the descending thoracic aorta. Many animal models of spinal cord ischemia have been utilized to examine the efficacy of various neuroprotective methods. In this study, we establish a rabbit model of spinal cord ischemia by selective temporary occlusion of lumbar arteries and examine the protective effects of systemic mild hypothermia in this model. Animals were divided into the following four groups: sham group (group A, n = 6); 10 min ischemia, normothermia (39 degrees C) (group B, n = 6); 20 min ischemia, normothermia (group C, n = 6); and 30 min ischemia, mild hypothermia (35 degrees C) (group D, n = 6). After 7 d of reperfusion, three rabbits in group B and five rabbits in group C developed paraplegia (Tarlov's score = 0). In contrast, all rabbits preserved hindlimb motor function (Tarlov's score = 4) in groups A and D. Histological findings indicated that the number of motor neurons in the anterior horns in group C were significantly fewer than in group A. A large number of motor neurons were preserved in group D. Hypothermia is known to be an effective and reliable method of neuroprotection, but the risk of complications rises at deep hypothermia. Our current results confirm that systemic, mild hypothermia is a safe and effective neuroprotective method during ischemia-reperfusion injury of the spinal cord.

  11. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism

    PubMed Central

    Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE. PMID:27798647

  12. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism.

    PubMed

    Tang, Zhiyuan; Wang, Xudong; Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie; Ni, Songshi

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.

  13. 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

  14. A novel method for blood volume estimation using trivalent chromium in rabbit models

    PubMed Central

    Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S.; Rawat, Dinesh; Binu, V. S.; Karun, Kalesh M.

    2014-01-01

    Background: Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. Aims: The aim was to compare blood volume estimations using trivalent chromium [51Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Materials and Methods: Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of 51Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using 51Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using 51Cr(III). Results: The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using 51Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using 51Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). Conclusions: The estimation of blood volume using 51Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using 51Cr(III) to find its application in acute clinical settings. PMID:25190922

  15. Anatomic and histological study of the rabbit mandible as an experimental model for wound healing and surgical therapies.

    PubMed

    Campillo, V-E; Langonnet, S; Pierrefeu, A; Chaux-Bodard, A-G

    2014-10-01

    The rabbit is one of the most widely used models for studying bone remodeling or dental implant osseointegration but very few data are available about the rabbit's mandible. The aim of this work was to describe the anatomy of the rabbit mandible and to estimate the available bone volume for experimental studies. First, with a dissection, the morphology of the mandible was described and the mental foramen, the position of the main salivary glands and muscular insertions were located. Then, by X-ray imaging, the position of the inferior alveolar canal, the dental root courses and volume and bone density were described. Finally, with frontal sections of the mandible body, the rabbit's dental and alveolar bone histological structure were assessed. Thus, the relevance of the rabbit mandible as an experimental model for wound healing or surgical therapies was discussed.

  16. 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.

    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.

  17. Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

    PubMed Central

    Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar

    2014-01-01

    Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609

  18. Bone response to porous polymethylmethacrylate cement loaded with hydroxyapatite particles in a rabbit mandibular model.

    PubMed

    Sa, Yue; Yu, Na; Wolke, Joop G C; Chanchareonsook, Nattharee; Goh, Bee Tin; Wang, Yining; Yang, Fang; Jansen, John A

    2017-04-03

    The aim of the current study was to evaluate bone formation and tissue response to porous polymethylmethacrylate (PMMA) cement with or without hydroxyapatite (HA) in a rabbit mandibular model. Therefore, fourteen New Zealand white rabbits were randomly divided into two groups of seven according to the designed study end points of 4 and 12 weeks. For each rabbit, two decorticated defects (6 mm in height and 10 mm in width for each) were prepared at both sides of the mandible. Subsequently, the defects were filled with respectively porous PMMA and porous PMMA-HA cement. After reaching the designated implantation period, the rabbits were euthanized and the mandibles were retrieved for histological analysis. Results showed that both porous PMMA and porous PMMA-HA supported bone repair. Neither of the bone cements caused significant inflammation to nerve or other surrounding tissues. After implantation of 12 weeks, majority of the porosity was filled with newly formed bone for both cements, which supports the concept that a porous structure within PMMA can enhance bone ingrowth. Histomorphometrical evaluation, using histological grading scales, demonstrated that, at both implantation times, the presence of HA in the PMMA enhanced bone formation. Bone was always in direct contact with the HA particles, while intervening fibrous tissue was present at the PMMA-bone interface. On the basis of results, it was concluded that injectable porous PMMA-HA cement might be a good candidate for craniofacial bone repair, which should be further evaluated in a more clinically relevant large animal model.

  19. 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.

  20. Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion

    PubMed Central

    Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

    2013-01-01

    Background Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. Objective To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. Methods A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3–L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Results Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). Conclusions The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury. PMID:23809530

  1. 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

  2. Sodium iodoacetate induced osteoarthrosis model in rabbit temporomandibular joint: CT and histological study (part I).

    PubMed

    Güler, N; Kürkçü, M; Duygu, G; Cam, B

    2011-11-01

    Studies to elucidate the pathophysiology of osteoarthrosis have been hampered by the lack of a rapid, reproducible animal model that mimics the histopathology and symptoms associated with the disease. The aim of this study is to evaluate the radiological, histological and histomorphometrical findings of four different concentrations of sodium iodoacetate (MIA) to create osteoarthrosis by using an arthrocentesis technique on rabbit temporomandibular joint (TMJ). 12 New Zealand white male rabbits received an injection of MIA (50 μl dose of 1.5, 2, 2.5, 3mg/ml concentrations) to a single joint of each group by arthrocentesis. Computed tomography (CT) images were obtained pre- and post-injections at 2, 4 and 6 weeks. Early osteoarthritic changes in the rabbit TMJ were found histologically at 4 weeks and with a 3mg/ml concentration of MIA. The mean subchondral bone volume depended on the concentration of MIA and was 62±2.6%, 63±4.1%, 42±3.6% and 38±3.8%, respectively. A minor abnormality was found on CT in six joints at the 4-week follow up. MIA injection and arthrocentesis offer a rapid and minimally invasive method of reproducing histologically osteoarthrotic lesions in the rabbit TMJ.

  3. 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.

  4. Lipoxin A4 ameliorates ischemia/reperfusion induced spinal cord injury in rabbit model

    PubMed Central

    Liu, Zhi-Qiang; Zhang, Hong-Bin; Wang, Jian; Xia, Li-Jian; Zhang, Wei

    2015-01-01

    Ischemia/reperfusion (I/R) induced spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repairaortic aneurysms. This study aims to investigate the neuroprotective effects of Lipoxin A4 and its potential mechanism in a rabbit model with I/R spinal cord injury. Forty-five rabbits were randomly divided into three groups: sham group, I/R group and Lipoxin A4 group. Rabbits were subject to 30 min aortic occlusion to induce transient spinal cord ischemia. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, as well as local malondialdehyde (MDA) and total superoxide dismutase (SOD) activity analysis. All animals in the I/R group became paraplegic. While after 48-hour treatment, compared with I/R group, Lipoxin A4 significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). These results suggest that Lipoxin A4 can ameliorate I/R induced spinal cord injury in Rabbit through its antiapoptosis and antioxidant activity. PMID:26550197

  5. [Model for evaluating the risk of introducing rabbit viral hemorrhagic disease based on experience in Mexico].

    PubMed

    Heneidi Zeckua, A; Zepeda Sein, C; Mateos Poumián, A; Velázquez, G

    1997-04-01

    Viral haemorrhagic disease (VHD) of rabbits was introduced into Mexico from the United States of America in November 1988, following the importation of infected carcasses from China. In February 1989, the National System for Animal Health Emergencies was created, and an eradication programme was implemented at that time. The VHD virus was eradicated in 1992, by means of disease control procedures which included active epidemiological surveillance, publicity campaigns, slaughter, cleaning and disinfection of affected premises, the use of sentinel animals, serological monitoring and repopulation. The eradication programme involved the serological sampling of 39,727 rabbits (revealing an incidence of 1.4%) and the slaughter of 121,275 affected rabbits and rabbits at risk of exposure to infection. The final outbreak of the disease was recorded in April 1991. The country maintained strict epidemiological surveillance through serological testing, certification of premises free from the disease, and control of movement of animals and animal products. Mexico was declared free from the disease on 20 January 1993, becoming the first country to have eradicated VHD. The authors propose a model to evaluate the risk of introducing VHD through the importation of animals and animal products. A guide is provided to evaluate each branch of the relevant scenario tree and the principal criteria which indicate the event at each parameter.

  6. Platelet-Rich Plasma May Improve Osteochondral Donor Site Healing in a Rabbit Model

    PubMed Central

    Smyth, Niall A.; Haleem, Amgad M.; Ross, Keir A.; Hannon, Charles P.; Murawski, Christopher D.; Do, Huong T.; Kennedy, John G.

    2016-01-01

    Purpose The purpose of this study was to assess the effect(s) of platelet-rich plasma (PRP) on osteochondral donor site healing in a rabbit model. Methods Osteochondral donor sites 3 mm in diameter and 5 mm in depth were created bilaterally on the femoral condyles of 12 New Zealand White rabbits. Knees were randomized such that one knee in each rabbit received an intra-articular injection of PRP and the other received saline (placebo). Rabbits were euthanized at 3, 6, and 12 weeks following surgery. Repair tissue was evaluated using the International Cartilage Repair Society (ICRS) macroscopic and histological scores. Results No complications occurred as a result of the interventions. There was no significant difference in macroscopic scores between the 2 groups (5.5 ± 3.8 vs. 3.8 ± 3.5; P = 0.13). Subjective macroscopic assessment determined greater tissue infill with fewer fissures and a more cartilage-like appearance in PRP-treated knees. Overall ICRS histological scores were better in the PRP group compared with the placebo (9.8 ± 2.0 vs. 7.8 ± 1.8; P = 0.04). Histological scores were also higher in the PRP group compared with the placebo group at each time point. Greater glycosaminoglycan and type II collagen content were noted in the repair tissue of the PRP group compared with the placebo group. Conclusion The results of this study indicate that PRP used as an intra-articular injection may improve osteochondral healing in a rabbit model. PMID:26958322

  7. Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1*

    PubMed Central

    Li, Li; Zhang, Quanjun; Yang, Huaqiang; Zou, Qingjian; Lai, Chengdan; Jiang, Fei; Zhao, Ping; Luo, Zhiwei; Yang, Jiayin; Chen, Qian; Wang, Yan; Newsome, Philip N.; Frampton, Jon; Maxwell, Patrick H.; Li, Wenjuan; Chen, Shuhan; Wang, Dongye; Siu, Tak-Shing; Tam, Sidney; Tse, Hung-Fat; Qin, Baoming; Bao, Xichen; Esteban, Miguel A.; Lai, Liangxue

    2017-01-01

    Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH−/− rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH−/− rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH−/− rabbits are an attractive alternative for modeling the consequences of HT1. PMID:28053091

  8. Pre-treatment with simvastatin prevents the induction of diet-induced atherosclerosis in a rabbit model

    PubMed Central

    Oikonomidis, Nikolaos; Kavantzas, Nikolaos; Korou, Laskarina-Maria; Konstantopoulos, Panagiotis; Pergialiotis, Vasilios; Misiakos, Evangelos; Rizos, Ioannis; Verikokos, Christos; Perrea, Despina N.

    2016-01-01

    The aim of the present study was to investigate the potential antiatherosclerotic activities of simvastatin in rabbits. Twenty-two, male, New Zealand rabbits were divided into the following groups: Control group (group C); cholesterol group (group A), in which the rabbits were fed a commercial rabbit chow supplemented with 0.5% w/w cholesterol for 8 weeks and then fed with normal chow for an additional 8 weeks; and a treatment group (group B), in which the rabbits initially received standard commercial rabbit chow along with being administered simvastatin for 8 weeks, following which they consumed a high-cholesterol diet for a further 8 weeks. The rabbits pre-treated with simvastatin presented significantly lower serum cholesterol and low-density lipoprotein cholesterol levels when compared with the non simvastatin-treated cholesterol-fed animals. Furthermore, none of the rabbits in the simvastatin group presented with atherosclerotic lesions in the aorta. Thus, simvastatin was demonstrated to exhibit preventive properties against the formation of atherosclerosis in the atherosclerosis model in the current study, predominantly via its hypolipidemic activity. PMID:28101339

  9. Establishment of a Rabbit Model of Chronic Obstructive Sleep Apnea and Application in Cardiovascular Consequences

    PubMed Central

    Xu, Li-Fang; Zhou, Xiu-Fang; Hu, Ke; Tang, Si; Luo, Yu-Chuan; Lu, Wen

    2017-01-01

    Background: Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress. Methods: The rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography. Results: After 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2 showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-α increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264

  10. A proposed model of naturally occurring osteoarthritis in the domestic rabbit.

    PubMed

    Arzi, Boaz; Wisner, Erik R; Huey, Daniel J; Kass, Philip H; Hu, Jerry; Athanasiou, Kyriacos A

    2011-12-19

    Osteoarthritis affects one in eight American adults over the age of 25 y and is a leading cause of chronic disability in the US. Translational research to investigate treatments for this naturally occurring joint disease requires an appropriate animal model. The authors conducted a retrospective study to assess the potential of naturally occurring osteoarthritis in the domestic rabbit as a model of the human disease. Analysis of radiographic images showed that the presence and severity of osteoarthritis were significantly influenced by both age and body weight. The most commonly affected joints were the knee and the hip. The findings reported here suggest that the rabbit is an excellent model of spontaneously arising osteoarthritis that may be useful in translational research pertaining to the human disease.

  11. New models of chronic synovitis in rabbits induced by mycoplasmas: microbiological, histopathological, and immunological observations on rabbits injected with Mycoplasma arthritidis and Mycoplasma pulmonis.

    PubMed Central

    Cole, B C; Griffiths, M M; Eichwald, E J; Ward, J R

    1977-01-01

    A dose-dependent chronic synovitis was induced in rabbit knees after the intra-articular injection of both Mycoplasma arthritidis and Mycoplasma pulmonis. The inflammation progressed from an initial acute phase at 1 week characterized by edema, infiltration of the synovium with monocytes and heterophils, and desquamation of lining cells, to a more chronic phase at 1 and 3 months, in which villus hyperplasia, lymph "nodules," mononuclear cell infiltration, fibroplasia, and collagen deposition were prominent. With one exception, mycoplasmas could no longer be cultivated from the joints 1 month postinoculation. Both mycoplasma species evoked a humoral antibody response that was more marked in synovial fluids than in peripheral blood. A cell-mediated immune reaction, as evidence by enhanced uptake by [3H]thymidine by sensitized blood, spleen, or node lymphocytes in the presence of homologous antigen, was detected only in rabbits injected with M. pulmonis. Lymphocytes taken from arthritic rabbits were no more cytotoxic toward synovial cells derived from normal or arthritic rabbits than were normal lymphocytes. The models of synovitis described in this study offer a convenient probe for determining the mechanisms of mycoplasma-induced inflammation, since they require only a single injection of the initiating agent and, in addition, utilize an animal host large enough for detailed investigation into the nature of mycoplasma/synovium interactions. Images PMID:873616

  12. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model.

    PubMed Central

    Green, M T; Rosborough, J P; Dunkel, E C

    1981-01-01

    The rabbit provides an excellent model for the study of ocular herpes because herpetic keratitis in the rabbit eye resembles human disease in its clinical features and in its propensity for spontaneous recurrence. This paper presents a method for the electrical induction of multiple episodes of in vivo reactivation of latent HSV-1 infection with peripheral shedding of virus. Physiological levels of current delivered via an electrode implanted over the trigeminal ganglion of latently infected animals has enabled us to modify and synchronize virus shedding in preocular tear film and to cause multiple episodes of reactivation in a single animal. For this reason, the model is well suited for antiviral efficacy testing and provides an excellent opportunity for investigation of virus-host cell interactions in latent and recurring herpetic disease. Images PMID:6271686

  13. Is the rabbit ear model, in its present state, prophetic of acnegenicity?

    PubMed

    Frank, S B

    1982-03-01

    The rabbit ear model has been proposed as a useful bioassay to establish the comedogenic and acnegenic qualities of chemical compounds and finished products, pharmaceutical and cosmetic, for topical application. This review highlights the many problems in performance of the test method, the absence of correlation with experience in the human, and, consequently, the serious limitations of the conclusions that can reasonably be drawn, especially for the clinical dermatologist.

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

    PubMed

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

    2014-10-01

    Hemocompatibility is the goal for any biomaterial contained in extracorporeal life supporting 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 extracorporeal life supporting. 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 extracorporeal life supporting longevity. These novel biomaterials may improve extracorporeal circulation hemocompatibility by preserving near resting physiology of the major blood components, the platelets and monocytes. The rabbit extracorporeal circulation 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.

  15. 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

  16. Evaluating Loading Deflection of Distraction Osteogenic Rib in a Rabbit Model

    PubMed Central

    Shen, Weimin; Tang, Chenlu; Yang, Junyi; Kong, Liangliang

    2016-01-01

    Background: The treatment of patients with partially atrophic rib and rib defects requires an ideal arc of the rib that has adequate bone length and width. To design and assemble a distraction device with a strain gauge, we need to establish an animal model for testing it during rib distraction osteogenesis. Methods: Osteotomies were performed at the same position in the fifth rib in 8 rabbits. Customized distraction devices attached to strain gauges were used to distract the ribs. After a month of distraction and consolidation, loading deflection gauges were used, and specimens were examined histologically to record bone formation. Results: Distraction osteogenesis was carried out successfully in all rabbits when the device used to distract the rib up to 4 cm. Conclusions: The device can be used for strain testing during rib distraction osteogenesis performed in a rabbit model. There was no significant difference in the loading deflection gauges of the bone between osteogenic and contralateral ribs. This animal model of costal distraction osteogenesis is successful. PMID:27826456

  17. 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.

  18. 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

  19. 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.

  20. Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model.

    PubMed

    Rölfing, Jan Hendrik Duedal; Bendtsen, Michael; Jensen, Jonas; Stiehler, Maik; Foldager, Casper Bindzus; Hellfritzsch, Michel Bach; Bünger, Cody

    2012-07-01

    We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p<0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.

  1. Development of a new model for acute myocardial infarction in rabbits

    PubMed Central

    TAN, Mei-Yun; XIA, Bo; XIAO, Zhun; FAN, Zhong-Wei; ZHOU, Hong; GUO, Xing; HUANG, Yong-Can

    2017-01-01

    The rabbit left anterior descending coronary artery is not macroscopically apparent; this often leads to failure in creation of an acute myocardial infarction (AMI) model. In order to devise a simple method with good reproducibility and high success rate for use as a rabbit AMI model, a new surgical technique was developed, in which the obtuse marginal (OM) branch of the left circumflex coronary artery was coagulated with an electric knife using a left parasternal approach. Four weeks after OM branch coagulation, an electrocardiogram (ECG), blood biochemistry analysis, echocardiographic measurements and pathologic analysis were performed. The left parasternal approach provided the surgeon clear visualization of the targeted blood vessel to accurately identify the proper site to occlude. The successful development of AMI was confirmed by ST segment elevation on the ECG, by high levels of AMI-related markers in blood samples, by cardiac functional damage reflected on echocardiographic images and by changes in pathological sections. Furthermore, an acceptable success rate and low mortality were achieved. Hence, this surgical technique was suggested to be a highly reliable and reproducible method to induce AMI in rabbits for the assessment of new therapeutic interventions or regenerative approaches. PMID:28111375

  2. Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.

    PubMed

    Wang, Lei; Zhou, Shuxia; Liu, Baolin; Lei, Delin; Zhao, Yinghua; Lu, Chao; Tan, Aixing

    2006-12-01

    Distraction osteogenesis is widely used in treating deformities, defects, and fractures of both long bones and craniofacial bones. Demands for acceleration of bone consolidation are increased in distraction osteogenesis. Nerve growth factor (NGF) can enhance innervation and bone regeneration in a fracture model and stimulate differentiation of osteoblastic cells. In this study, we tested the ability of locally applied NGF to enhance bone regeneration in a rabbit model of mandibular distraction osteogenesis. Twenty rabbits underwent bilateral distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human NGFbeta (hNGFbeta) in buffer was injected into the callus after distraction. The contralateral side received placebo injections. Rabbits were euthanized at consolidation times of 14 and 28 days. Specimens were subjected to radiography, callus dimensions measurement, mechanical testing, and bone histological and histomorphometric analysis. The maximum load, bone volume/total volume, mineral apposition rate of the 1st to 11th day, and mineralized bone percentage were significantly higher in the hNGFbeta side at 14 and 28 days (p<0.05). The data indicate that locally applied hNGFbeta can accelerate callus maturation and may be an option to shorten the consolidation period in distraction osteogenesis.

  3. 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

  4. Atomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography.

    PubMed

    Wang, Xue; Xu, Fengting; Liu, Jiasen; Gao, Bingquan; Liu, Yanxin; Zhai, Yujia; Ma, Jun; Zhang, Kai; Baker, Timothy S; Schulten, Klaus; Zheng, Dong; Pang, Hai; Sun, Fei

    2013-01-01

    Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 Å resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 Å resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ~5.5 Å, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection.

  5. Anti-inflammatory cytokine TSG-6 inhibits hypertrophic scar formation in a rabbit ear model.

    PubMed

    Wang, Hui; Chen, Zhao; Li, Xiao-Jing; Ma, Li; Tang, Yue-Ling

    2015-03-15

    Hypertrophic scars are characterized by excessive fibrosis and extracellular matrix (ECM) deposition and can be functionally and cosmetically problematic; however, there are few satisfactory treatments for controlling hypertrophic scars. The inflammatory cells and cytokines involved in excessive inflammation during wound healing facilitate fibroblast proliferation and collagen deposition, leading to pathologic scar formation. TSG-6 exhibits anti-inflammatory activity. This study examined the effect of recombinant TSG-6 on inflammation in hypertrophic scars using a rabbit ear model. Six 7-mm, full-thickness, circular wounds were made on the ears of 12 rabbits. TSG-6 and PBS were intradermally injected into the right and left ear wounds, respectively. The methods of TEM and TUNEL were used to detect fibroblast apoptosis. The expressions of inflammatory factors: IL-1β, IL-6 and TNF-α, were detected by immunohistochemistry and real time polymerase chain reaction. Collagen I and III expression detected by immunohistochemistry and Masson׳s trichrome staining and SEI (scar elevation index) was used to evaluate the extent of scarring. TSG-6 injection mitigated the formation of a hypertrophic scar in the rabbit ear. TSG-6-treated wounds exhibited decreased inflammation compared with the control group, as evidenced by the lower levels of IL-1β, IL-6, TNF-α and MPO. The SEI and the synthesis of collagens I and III were significantly decreased in the TSG-6-treated scars compared with control scars. The apoptosis rate was higher in the TSG-6-treated scars. TSG-6 exhibited anti-inflammatory effects during the wound healing process and cicatrization and significantly diminished hypertrophic scar formation in a rabbit ear model.

  6. Expression of Neuropeptides and Cytokines in a Rabbit Model of Diabetic Neuroischemic Wound-Healing

    PubMed Central

    Nabzdyk, Leena Pradhan; Kuchibhotla, Sarada; Guthrie, Patrick; Chun, Maggie; Auster, Michael E; Nabzdyk, Christoph; Deso, Steven; Andersen, Nicholas; LoGerfo, Frank W.; Veves, Aristidis

    2013-01-01

    Objective The present study is designed to understand the contribution of peripheral vascular disease and peripheral neuropathy to the wound-healing impairment associated with diabetes. Using a rabbit model of diabetic neuroischemic wound-healing we investigated rate of healing, leukocyte infiltration and expression of cytokines, Interleukin (IL)-8 and IL-6, and, neuropeptides, Substance P (SP) and Neuropeptide Y (NPY). Design of study Diabetes was induced in White New Zealand rabbits by administering alloxan while control rabbits received saline. Ten days later animals in both groups underwent surgery. One ear served as a sham and the other was made ischemic (ligation of central+rostral arteries), or neuroischemic (ischemia+ resection of central+rostral nerves). Four, 6mm punch biopsy wounds were created in both ears and wound-healing was followed for ten days using computerized planimetry. Results Non-diabetic sham and ischemic wounds healed significantly more rapidly than diabetic sham and ischemic wounds. Healing was slowest in neuroischemic wounds, irrespective of diabetic status. A high M1/M2 macrophage ratio and a high pro-inflammatory cytokine expression, both indicators of chronic-proinflammatory state, and low neuropeptide expression were seen in pre-injury diabetic skin. Post-injury, in diabetic wounds M1/M2 ratio remained high, the reactive increase in cytokine expression was low and neuropeptide expression was further decreased in neuroischemic wounds. Conclusion This rabbit model illustrates how a combination of a high M1/M2 ratio, a failure to mount post-injury cytokine response as well as a diminished neuropeptide expression contribute to wound-healing impairment in diabetes. The addition of neuropathy to ischemia leads to equivalently severe impaired wound-healing irrespective of diabetes status, suggesting that in the presence of ischemia, loss of neuropeptide function contributes to the impaired healing associated with diabetes. PMID:23755976

  7. Pacemaker activity of the rabbit sinoatrial node. A comparison of mathematical models.

    PubMed Central

    Wilders, R; Jongsma, H J; van Ginneken, A C

    1991-01-01

    In the past decade, three mathematical models describing the pacemaker activity of the rabbit sinoatrial node have been developed: the Bristow-Clark model, the Irisawa-Noma model, and the Noble-Noble model. In a comparative study it is demonstrated that these models, as well as subsequent modifications, all have several drawbacks. A more accurate model, describing the pacemaker activity of a single pacemaker cell isolated from the rabbit sinoatrial node, was constructed. Model equations, including equations for the T-type calcium current, are based on experimental data from voltage clamp experiments on single cells that were published during the last few years. In contrast to the other models, only a small amount of background current contributes to the overall electrical charge flow. The action potential parameters of the model cell, its responses to voltage clamp steps and its current-voltage relationships have been computed. The model is used to discuss the relative contribution of membrane current components to the slow diastolic depolarization phase of the action potential. PMID:1722117

  8. Determination of oocyte membrane permeability coefficients and their application to cryopreservation in a rabbit model.

    PubMed

    Liu, Jun; Mullen, Steve; Meng, Qinggang; Critser, John; Dinnyes, Andras

    2009-10-01

    Having an effective means to cryopreserve human oocytes would offer more flexibility in healthcare services for infertility patients, and obviate cryopreservation of preimplantation embryos. It is essential to establish good animal models for human oocyte cryopreservation and the rabbit is a good candidate. Attempts to improve oocyte cryopreservation are often empirical, with results often being irreproducible. Cryopreservation protocols may be optimized by modeling the changes in oocyte volume and the associated damages incurred during the addition and dilution of cryoprotective agents (CPA). The objectives of the current study were to determine cryobiological properties of rabbit oocytes, including the isotonic volume, osmotically inactive cell fraction (V(b)), hydraulic conductivity (L(p)), permeability (P(s)) to dimethylsulfoxide (Me(2)SO), ethylene glycol (EG), and glycerol (GLY) and to examine the correlation between cell volume excursions and viability. This has led to the development of the accumulative osmotic damage (AOD) model associated with the processes of CPA addition/dilution. Mature rabbit oocytes were perfused with 15% (V/V) CPA medium (dissolved in 1x PBS). The osmotic responses of the oocytes were videotaped. A two-parameter model was fit to the experimental data to determine the values of L(p) and P(s). Oocyte volumes reached upon equilibration with 285, 600, 900, and 1200 mOsm (milliosmolal) solutions of non-permeating compounds were plotted in a Boyle van't Hoff plot. The average radius of rabbit oocytes in an isotonic solution was determined to be 55.7+/-1.2 microm (n=16). The rabbit oocyte exhibited an "ideal" osmotic response in the range from iso-osmolity to 1200 mOsm. The V(b) was determined to be 20% of the isotonic value with r(2)=0.97. The values of L(p) were determined to be 0.79+/-0.26, 0.82+/-0.22, and 0.64+/-0.16 microm min(-1)atm(-1) and the P(s) values were determined to be 2.9+/-1.3, 2.7+/-1.3, and 0.27+/-0.18x10(-3) cm min(-1

  9. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    PubMed Central

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Le Grand, Roger; Fomsgaard, Anders

    2013-01-01

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. PMID:26344115

  10. [Electrophysiological analysis of bruxisma of rabbits as natural model of the first bruxism in human being].

    PubMed

    Ignatova, Iu P; Kromin, A A

    2010-01-01

    In chronic experiences on 5 rabbits subjected to airmentary deprivation, impulse activity of the chewing muscles before and after the food was given to them was studied. It has been established, that flashes of bruxism nonoperiodically arise in rabbits in conditions of hunger and satiation and are shown in electric activity of masseter and mylohyoideus muscles in the form of burst type phase impulse activity of MU. Bruxism in conditions of hunger and satiation reflects in the same type way in structure of the time organization of impulse activity of the chewing muscles in the form of bimodal distributions of interpulse intervals and monomodal distributions of periods of the burst type rhythmic of action potentials. The alimentary motivation exerts inhibitory modulating influence on frequency of phase discharge activity of chewing center motoneurons in medulla oblongata and frequency of generation of the action potentials' bursts by the chewing muscles participating in bruxism. Impulse activity of chewing muscles during bruxism and food intake behaviour has the same-type character. Bruxism arises due to reorganization of the impulse activity of chewing center motoneurons innervating masseter and mylohyoideus muscles. There is no basis to suppose the presence of the special center of bruxism in medulla oblongata.Bruxism in rabbits an be considered as natural model of the first type bruxism in man.

  11. Effects of MK-886, a leukotriene biosynthesis inhibitor, in a rabbit model of endotoxic shock.

    PubMed

    Can, C; Cinar, M G; Ulker, S; Evinç, A; Koşay, S

    1998-06-05

    Leukotrienes are one of the biological mediators that play a role in endotoxic shock. In this study, we investigated the effects of a leukotriene biosynthesis inhibitor, MK-886, in a rabbit model of endotoxic shock. Lipopolysaccharide (Escherichia coli serotype 055:B5) infusion (1 mg kg(-1) h(-1)) to rabbits caused a biphasic decline in arterial blood pressure and decreased the vasoresponsiveness to phenylephrine, potassium chloride, sodium nitroprusside and acetylcholine in abdominal aortic rings. Oral administration of MK-886 (3-(1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl(-2,2-+ ++dimethylpropanoic acid) (5 mg/kg) 3 h prior to lipopolysaccharide infusion significantly inhibited the decline in arterial blood pressure and enhanced the responsiveness to phenylephrine and acetylcholine, whereas the changes in sodium nitroprusside and potassium chloride responses were not significant. However, the pD2 (-log EC50) values for sodium nitroprusside in this group were higher than those of the group that received lipopolysaccharide alone. Neither the administration of the vehicle alone to endotoxemic rabbits, nor MK-886 administration to control animals, caused significant changes. These data suggest that MK-886 attenuates the hypotension and partially reverses the impaired vascular responsiveness observed in endotoxic shock.

  12. Manchette-acrosome disorders during spermiogenesis and low efficiency of seminiferous tubules in hypercholesterolemic rabbit model

    PubMed Central

    Simón, Layla; Funes, Abi K.; Yapur, Martín A.; Cabrillana, María E.; Monclus, María A.; Boarelli, Paola V.; Vincenti, Amanda E.

    2017-01-01

    hypercholesterolemic rabbit model is a useful tool to study serum cholesterol increment linked to sub/infertility. PMID:28241054

  13. 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

  14. 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

  15. Manchette-acrosome disorders during spermiogenesis and low efficiency of seminiferous tubules in hypercholesterolemic rabbit model.

    PubMed

    Simón, Layla; Funes, Abi K; Yapur, Martín A; Cabrillana, María E; Monclus, María A; Boarelli, Paola V; Vincenti, Amanda E; Saez Lancellotti, Tania E; Fornés, Miguel W

    2017-01-01

    rabbit model is a useful tool to study serum cholesterol increment linked to sub/infertility.

  16. 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.

  17. Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

    PubMed Central

    Toshida, Hiroshi; Nguyen, Doan H.; Beuerman, Roger W.; Murakami, Akira

    2010-01-01

    PURPOSE To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit. METHODS Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes. RESULTS In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle- treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested. CONCLUSIONS These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow. PMID:19218606

  18. Whole muscle length-tension relationships are accurately modeled as scaled sarcomeres in rabbit hindlimb muscles.

    PubMed

    Winters, Taylor M; Takahashi, Mitsuhiko; Lieber, Richard L; Ward, Samuel R

    2011-01-04

    An a priori model of the whole active muscle length-tension relationship was constructed utilizing only myofilament length and serial sarcomere number for rabbit tibialis anterior (TA), extensor digitorum longus (EDL), and extensor digitorum II (EDII) muscles. Passive tension was modeled with a two-element Hill-type model. Experimental length-tension relations were then measured for each of these muscles and compared to predictions. The model was able to accurately capture the active-tension characteristics of experimentally-measured data for all muscles (ICC=0.88 ± 0.03). Despite their varied architecture, no differences in predicted versus experimental correlations were observed among muscles. In addition, the model demonstrated that excursion, quantified by full-width-at-half-maximum (FWHM) of the active length-tension relationship, scaled linearly (slope=0.68) with normalized muscle fiber length. Experimental and theoretical FWHM values agreed well with an intraclass correlation coefficient of 0.99 (p<0.001). In contrast to active tension, the passive tension model deviated from experimentally-measured values and thus, was not an accurate predictor of passive tension (ICC=0.70 ± 0.07). These data demonstrate that modeling muscle as a scaled sarcomere provides accurate active functional but not passive functional predictions for rabbit TA, EDL, and EDII muscles and call into question the need for more complex modeling assumptions often proposed.

  19. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

    PubMed

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

    2008-01-15

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

  20. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    PubMed Central

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G.; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35–37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing. PMID:18160660

  1. Osteogenic Effects of Dedifferentiated Fat Cell Transplantation in Rabbit Models of Bone Defect and Ovariectomy-Induced Osteoporosis

    PubMed Central

    Kikuta, Shinsuke; Tanaka, Nobuaki; Kazama, Tomohiko; Kazama, Minako; Kano, Koichiro; Ryu, Junnosuke; Tokuhashi, Yasuaki

    2013-01-01

    We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a β-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the β-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis. PMID:23566022

  2. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bone defect and ovariectomy-induced osteoporosis.

    PubMed

    Kikuta, Shinsuke; Tanaka, Nobuaki; Kazama, Tomohiko; Kazama, Minako; Kano, Koichiro; Ryu, Junnosuke; Tokuhashi, Yasuaki; Matsumoto, Taro

    2013-08-01

    We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a β-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the β-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis.

  3. Inhibition of Receptor-Interacting Protein Kinase 1 with Necrostatin–1s ameliorates disease progression in elastase-induced mouse abdominal aortic aneurysm model

    PubMed Central

    Wang, Qiwei; Zhou, Ting; Liu, Zhenjie; Ren, Jun; Phan, Noel; Gupta, Kartik; Stewart, Danielle M.; Morgan, Stephanie; Assa, Carmel; Kent, K. Craig; Liu, Bo

    2017-01-01

    Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s). Seven days after aneurysm induction by elastase perfusion, mice were randomly administered DMSO, Nec-1 (3.2 mg/kg/day) and Nec-1s (1.6 mg/kg/day) via intraperitoneal injection. Upon sacrifice on day 14 postaneurysm induction, the aortic expansion in the Nec-1s group (64.12 ± 4.80%) was significantly smaller than that of the DMSO group (172.80 ± 13.68%) (P < 0.05). The mean aortic diameter of Nec-1 treated mice appeared to be smaller (121.60 ± 10.40%) than the DMSO group, though the difference was not statistically significant (P = 0.1). Histologically, the aortic structure of Nec-1s-treated mice appeared normal, with continuous and organized elastin laminae and abundant αActin-expressing SMCs. Moreover, Nect-1s treatment diminished macrophage infiltration and MMP9 accumulation and increased aortic levels of tropoelastin and lysyl oxidase. Together, our data suggest that pharmacological inhibition of necroptosis with Nec-1s stabilizes pre-existing aneurysms by diminishing inflammation and promoting connective tissue repair. PMID:28186202

  4. Inhibition of Receptor-Interacting Protein Kinase 1 with Necrostatin-1s ameliorates disease progression in elastase-induced mouse abdominal aortic aneurysm model.

    PubMed

    Wang, Qiwei; Zhou, Ting; Liu, Zhenjie; Ren, Jun; Phan, Noel; Gupta, Kartik; Stewart, Danielle M; Morgan, Stephanie; Assa, Carmel; Kent, K Craig; Liu, Bo

    2017-02-10

    Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s). Seven days after aneurysm induction by elastase perfusion, mice were randomly administered DMSO, Nec-1 (3.2 mg/kg/day) and Nec-1s (1.6 mg/kg/day) via intraperitoneal injection. Upon sacrifice on day 14 postaneurysm induction, the aortic expansion in the Nec-1s group (64.12 ± 4.80%) was significantly smaller than that of the DMSO group (172.80 ± 13.68%) (P < 0.05). The mean aortic diameter of Nec-1 treated mice appeared to be smaller (121.60 ± 10.40%) than the DMSO group, though the difference was not statistically significant (P = 0.1). Histologically, the aortic structure of Nec-1s-treated mice appeared normal, with continuous and organized elastin laminae and abundant αActin-expressing SMCs. Moreover, Nect-1s treatment diminished macrophage infiltration and MMP9 accumulation and increased aortic levels of tropoelastin and lysyl oxidase. Together, our data suggest that pharmacological inhibition of necroptosis with Nec-1s stabilizes pre-existing aneurysms by diminishing inflammation and promoting connective tissue repair.

  5. MRI and Histopathologic Study of a Novel Cholesterol-Fed Rabbit Model of Xanthogranuloma

    PubMed Central

    Chen, Yuanxin; Hamilton, Amanda M.; Parkins, Katie M.; Wang, Jian-Xiong; Rogers, Kem A.; Zeineh, Michael M.; Rutt, Brian K.; Ronald, John A.

    2016-01-01

    Purpose To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination. Materials and Methods Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1-weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2-weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2∗ relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1, T2, and T2∗ values of lesions was performed. After imaging, brain specimens were examined using histological methods. Results In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6mm3 and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2∗ values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2∗ components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma. Conclusion Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. PMID

  6. A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup

    PubMed Central

    2016-01-01

    Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the “minimal physiological requirements” to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple “parsimonious” rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important “emergent” phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable

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

    USGS Publications Warehouse

    Germaine, Stephen S.; 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

  8. Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration.

    PubMed

    Jones, B W; Kondo, M; Terasaki, H; Watt, C B; Rapp, K; Anderson, J; Lin, Y; Shaw, M V; Yang, J-H; Marc, R E

    2011-10-01

    Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photoreceptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies.

  9. A rabbit model for sublingual drug delivery: comparison with human pharmacokinetic studies of propranolol, verapamil and captopril.

    PubMed

    Dali, Manisha M; Moench, Paul A; Mathias, Neil R; Stetsko, Paul I; Heran, Christopher L; Smith, Ronald L

    2006-01-01

    A rabbit model for investigating sublingual drug absorption was established yielding results consistent with clinical data reported in the literature. Using propranolol as a model compound the effect of formulation and dosing variables was explored as a means to characterize the limiting parameters of this model. In addition, verapamil and captopril were selected as reference compounds to compare this model to sublingual absorption in humans. Rabbits were dosed sublingually and systemic absorption was measured over time. Sublingual absorption of propranolol was dependent on dosing solution pH and volume. Intra-oral spray device did not affect the overall exposure compared to instillation using a syringe. Despite species and dosing regimen differences the relative bioavailabilities of propranolol and verapamil were very similar in rabbits and humans. In contrast, captopril absorption from the sublingual cavity of rabbits was low and did not agree with that observed in man. Here we report a sublingual rabbit model of drug delivery and its potential utility in preclinical development of intra-oral dosage forms.

  10. Rabbit rectus femoris muscle for ischemia-reperfusion studies: an improved model.

    PubMed

    Hoballah, J J; Mohan, C R; Schipper, P H; Chalmers, R T; Corry, D C; Corson, J D

    1996-11-01

    The rabbit rectus femoris muscle was evaluated as a potential model for skeletal muscle reperfusion injury studies. Six white New Zealand rabbits were used. On one randomly selected hind limb, ischemia was induced by direct clamping of the rectus femoris muscle's vascular pedicle. On the other side, blood flow was interrupted by clamping the femoral artery above and below the origin of the vascular pedicle that supplies the rectus femoris muscle. The duration of normothermic ischemia was 4 hr and was followed by 24 hr of normothermic reperfusion. The interruption and restoration of blood flow was monitored using a laser flow meter. The rectus femoris muscles were weighed on a suspension spring balance prior to ischemia and at the end of reperfusion to estimate edema. The extent of muscle necrosis was determined using planimetry following staining with nitroblue tetrazolium. The muscle necrosis obtained by direct clamping of the vascular pedicle (66.9 +/- 14.3%) was significantly greater than that obtained by indirect clamping (18.6 +/- 11.4%) (P < 0.03 by t test). Unlike the indirect clamping technique, direct clamping achieved a good magnitude of muscle necrosis, thus allowing that specific model to be used in skeletal muscle reperfusion injury studies. The muscle weight gain observed in the direct clamping muscle group was 19.8 +/- 9.0% and was significantly greater than that observed in the opposite group being 6.3 +/- 6.5% (P < 0.05 by t test). The rabbit rectus femoris muscle is a suitable model for evaluating skeletal muscle reperfusion injury provided that direct clamping of the vascular pedicle is utilized.

  11. Effects of synthetic androgens on liver function using the rabbit as a model.

    PubMed

    Hild, Sheri Ann; Attardi, Barbara J; Koduri, Sailaja; Till, Bruce A; Reel, Jerry R

    2010-01-01

    The objective of this study was to determine whether the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0-13 with 17α-methyltestosterone (MT) as a positive control and testosterone (T) as a negative control to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7, and 14, were determined. As expected, T (10 mg/kg/d) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/d) increased BSP retention, and AST, ALT, GGT, and SDH levels, indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/d) increased BSP retention and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/d did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/d. For the androgens that exhibited liver toxicity at 10 mg/kg/d (MT, DMAU, and MENT), a no-observed-effect level of 1 mg/kg/d was established. Overall ranking of the synthetic androgens from most to least hepatotoxic on the basis of percent BSP retention was: MT & DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury.

  12. Effects of Synthetic Androgens on Liver Function Using the Rabbit as a Model*†

    PubMed Central

    Hild, Sheri Ann; Attardi, Barbara J.; Koduri, Sailaja; Till, Bruce A.; Reel, Jerry R.

    2010-01-01

    The objective of this study was to determine if the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0–13 with 17α-methyltestosterone (MT), as a positive control, and testosterone (T), as a negative control, to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7 and 14, were determined. As expected, T (10 mg/kg/day) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/day) increased BSP retention, and AST, ALT, GGT, and SDH levels indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/day), increased BSP retention, and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/day did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/day. For the androgens that exhibited liver toxicity at 10 mg/kg/day (MT, DMAU, and MENT), a no observed effect level (NOEL) of 1 mg/kg/day was established. Overall ranking of the synthetic androgens from most to least hepatotoxic based on %BSP retention was: MT ≫ DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury. PMID:20378929

  13. 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

  14. In Vitro Correlate of Immunity in a Rabbit Model of Inhalational Anthrax

    DTIC Science & Technology

    2001-05-01

    Vaccine 19 (2001) 4768-4773 rn0’ www elsevier com/~ocate/vacc~ ne inh r In vitro correlate of immunity in a rabbit model of inhalational anthrax...unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 a U- n- 4 0 ld ~n en na is :ct an ne Ire...B. 1s ne at ed ~ d - Ln- M.L.M. Pitt et a/. / Vaccine 19 (2001) 4768-4773 4769 thrax in guinea pigs [lo] while it is very highly effective

  15. Immunotherapy for Alzheimer's disease: harnessing our knowledge of T cell biology using a cholesterol-fed rabbit model.

    PubMed

    Coico, Richard; Woodruff-Pak, Diana S

    2008-12-01

    This timely special issue of the Journal of Alzheimer's Disease provides the opportunity to examine interfaces between basic science and clinical medicine using animal models to develop more effective therapies for the treatment and, ideally, prevention of Alzheimer's disease (AD). That some patients with AD enrolled in a clinical trial to inoculate against amyloid-beta (Abeta) experienced a misdirected polarization of Th cells reminds us that our knowledge of T cell biology, immune regulation, and the precise functional properties of adjuvants is incomplete. We review this knowledge and consider the advantages of the rabbit for immunological studies. The langomorph species is proximate to primates on the phylogenetic scale, its amino acid sequence of Abeta is 97% identical to the human Abeta sequence, and the rabbit model system is extensively characterized on a form of associative learning with parallels in normal aging in rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits treated with Abeta immunotherapy generate high titer anti-Abeta responses. The cholesterol-fed rabbit model of AD with its close parallels to human genetics and physiology, along with its validity from molecular to cognitive levels as a model of human AD, provides a promising vehicle for development of immunotherapies.

  16. Comparison of microporous polysaccharide hemospheres and Ankaferd Blood Stopper in a rabbit epistaxis model.

    PubMed

    Yurttas, Veysel; Sereflican, Murat; Terzi, Elçin Hakan; Ozyalvaçlı, Gulzade; Kazaz, Hasan

    2016-04-01

    The aim of this study was to evaluate the histopathological impact, effectiveness, and safety of two hemostatic agents, Ankaferd Blood Stopper (ABS) and microporous polysaccharide hemospheres (MPH), in an experimental rabbit epistaxis model. Rabbits were randomly assigned, using a computerized random number generator, to the following three groups of six animals: group 1 (control, irrigated with saline); group 2 (ABS-treated); and group 3 (MPH-treated). In all groups, a standardized rabbit epistaxis model was used. Hemostasis time and extent of nasal bleeding were measured to compare the hemostatic effect of ABS and MPH among groups. Septums were removed for histopathological analysis, 7 days after the procedure. ABS reduced hemostasis time to 104.2 s and amount of bleeding to 20.5 mg. MPH reduced hemostasis time to 71.7 s and amount of bleeding to 11.5 mg. Mean bleeding time in wounds administered ABS and MPH was significantly shorter compared with wounds administered isotonic saline solution (p = 0.004). ABS and MPH application decreased bleeding significantly compared with the control group (p = 0.004). Bleeding time and amount in the MPH group was significantly reduced compared with the ABS group (p = 0.013 and p = 0.004, respectively). There was no significant difference in the histopathological evaluation results between the ABS, MPH, and control groups. Our data indicate that both ABS and MPH represent safe, effective, and fast-acting hemostatic agents in the management of epistaxis. MPH was more effective than ABS in terms of hemostasis time and amount of bleeding.

  17. Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

    PubMed Central

    Hodges, Ryan; Endo, Masayuki; La Gerche, Andre; Eixarch, Elisenda; DeKoninck, Philip; Ferferieva, Vessilina; D'hooge, Jan; Wallace, Euan M.; Deprest, Jan

    2013-01-01

    Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is

  18. 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.

  19. 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.

  20. 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

  1. Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Marchette, David; Mackie, Ryan S; Thran, Brandolyn

    2016-11-01

    There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.

  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.

  3. Perfusion of a cerebral protective solution enhances neuroprotection in a rabbit model of occlusion-reperfusion: prolonged cerebral dormancy time.

    PubMed

    Ye, Libin; Hua, Aiyuan; Dai, Bo; Lu, Tingting; Zhang, Zhaolin; Ye, Meilin; Weintraub, Michael; Li, Qingdi Quentin

    2014-01-01

    In the present study, we investigated the effect of a cerebral protective solution on prolongation of cerebral dormancy time in a rabbit model of occlusion-reperfusion. In a control group, rabbits were anesthetized and the four cerebral arteries (the left and right common carotid arteries and vertebral arteries) were occluded for 7.5 min followed by reperfusion. All six rabbits in the control group died. In contrast, a second group underwent perfusion of a cerebral protective solution for 15 min between artery occlusion and reperfusion. All six rabbits in this group survived. However, when the perfusion solution was changed to 5% glucose solution or rabbit plasma in two other groups, the rabbits in both the latter two groups also died. Neuroprotection was also observed when the protective solution was administered for 30-60 min after the onset of artery occlusion and before the return of blood flow (reperfusion). To understand the high rate of thrombotic stroke in the clinic, we assessed the influence of different organ tissue infusions on blood coagulation in vitro and found that blood clotting occurred faster in the presence of brain tissue infusion compared to liver, kidney, and heart tissue infusions. These results indicate a higher rate of thrombosis in brain tissue compared to any of the other tissues tested. The current study shows that perfusion of a cerebral protective solution produced a significant neuroprotective benefit in our rabbit model of occlusion-reperfusion, suggesting that administration of a cerebral protective solution may be an effective approach for the treatment of ischemic stroke.

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

    PubMed

    Liu, Jiayi; Li, Ning; Li, Li; Li, Danye; Liu, Kai; Zhao, Lingyun; Tang, Jintian; Li, Liya

    2013-12-01

    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.

  5. Role of Kruppel-like Factor 2 in Intracranial Aneurysm of the Rabbit Model.

    PubMed

    Wu, X; Zhang, J; Huang, Q; Yang, P; Chen, J; Liu, J

    2015-11-08

    We investigated expression of Kruppel—like factor 2 (KLF2) and its correlation with basilar artery blood flow rate in the hemodynamically induced aneurysm model built by different methods. New Zealand rabbits were randomly divided into sham—operated group, unilateral ligation of common carotid artery (CCA) group (UL group) and bilateral ligation of CCA group (BL group). Rabbits were cervix—cut to expose the arteries without ligation (sham group), with right—side ligation (UL group) and bilateral ligation (BL group), respectively. Skull Doppler ultrasound was used to measure basilar artery blood flow rate in each group at week 1, 2, 3, or 4 separately (n=6 for each time point). The animals were killed after the measurements. At each time point, 6 basilar artery bifurcates from each group were collected and sent for staining (HE, EVG, Masson and KLF2 immunohistochemistry staining), while another 6 basilar artery bifurcates were processed with KLF2 Western blotting. Results showed that the average blood flow rate did not change significantly among the 4 time points in the Sham group, but it was insignificantly smaller compared to the UL group. The average blood flow rate in the BL group was significantly higher than that in the other two groups. Pathological tests showed that according to the aneurysm evaluation criteria, the basilar arteries in the Sham group had smooth tip lumina, complete endothelial cells, complete internal elastic membranes, but no fracture, thinning or aneurysm formation. Only 1 of 24 rabbits in the UL group had slight bulges in the tip of basilar artery, though not very severe. Twelve rabbits in the BL group had aneurysmal bulges, significantly different from the other two groups. KLF2 protein expression was not changed significantly with time in the Sham group, but increased slightly with time in the UL group. KLF2 protein expression in the BL group increased significantly only after 1 week and then maintained a high level

  6. 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

  7. 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

  8. In vitro eye irritancy test of lauryl derivatives using the reconstructed rabbit corneal epithelium model.

    PubMed

    Matsuda, Sanae; Hisama, Masayoshi; Shibayama, Hiroharu; Itou, Norihiko; Iwaki, Masahiro

    2009-06-01

    The rabbit corneal epithelium model (RCE model) was developed as a three-dimensional in vitro model to replace animal testing for the assessment of eye tolerance. In the model, a stratified culture of rabbit corneal epithelial cells is grown at the air-liquid interface on an amniotic membrane acting as a parabasal membrane. The alkaline exposure was restored each day in the presence of no irritants, although with the addition of SLS, which is a major irritant, the restoration of deficit was inhibited on the RCE model in a dose-dependent manner. The results of this test were comparable with those of the Draize test, and thus, this method using the RCE model may prove to be a useful and sensitive in vitro eye irritation test. The lauryl fatty chain derivatives, such as polyoxyethylene (9) lauryl ether (PLE), sodium polyoxyethylene (2) lauryl ether sulfate (SPLE), mono glyceryl laurate (MGL), and sodium N-lauroyl-l-glutaminate (SLG), which are widely used as surfactants for toiletry products and cosmetics, were evaluated for in vitro eye irritation potential using the RCE model. SLS, PLE, SPLE, MGL, and SLG inhibited 88.7%, 59.2%, 69.0%, 47.5%, and 15.7% of the restoration of deletion 24h after treatment at a concentration of 0.05%. The IC(50) (50% inhibitory concentration) values of SLS, PLE, SPLE, MGL, and SLG were 0.002%, 0.021%, 0.005%, 0.056%, and 0.448%, respectively. These results indicated that a functional group at the end of lauryl chain is an important factor for inhibiting the restoration of deletion using the RCE model.

  9. Acetylsalicylic acid combined with diclofenac inhibits cartilage degradation in rabbit models of osteoarthritis.

    PubMed

    Liu, Jianqiang; Wu, Changshun; Wang, Dong; Wang, Laicheng; Sun, Shui

    2016-10-01

    The present study aimed to investigate the effect of different concentrations of acetylsalicylic acid combined with diclofenac on the articular cartilage of a rabbit model of osteoarthritis (OA). A total of 40 New Zealand white rabbits were divided into 5 groups. Group A was a sham-operated control group, which was treated with normal saline. Groups B-E were OA models and were treated with normal saline and acetylsalicylic acid combined with diclofenac at concentrations of 5, 10 and 20 mg/kg, respectively. A cartilage macroscopic examination and a pathological observation were performed to analyze the structure of the articular cartilage in all of the treated groups. The nitric oxide (NO) content and interleukin 1β (IL-1β) levels were detected by an enzyme-linked immunosorbent assay. In addition, the protein expression of matrix metalloproteinase 3 (MMP)-3 and MMP-13 were detected by western blot analysis. The mRNA expression of tissue inhibitor of metalloproteinases 1 (TIMP1) was detected by polymerase chain reaction (PCR). The results revealed that different concentrations of the drugs significantly reduced the scores of cartilago articularis, the NO and IL-1β levels and the protein expression of MMP-3 and MMP-13. Furthermore, PCR revealed that the mRNA expression of TIMP1 was significantly upregulated, and the effects increased with increasing drug concentration. Thus, the administration of different concentrations of acetylsalicylic acid combined with diclofenac demonstrates preventive or therapeutic effects against OA progression.

  10. Acetylsalicylic acid combined with diclofenac inhibits cartilage degradation in rabbit models of osteoarthritis

    PubMed Central

    Liu, Jianqiang; Wu, Changshun; Wang, Dong; Wang, Laicheng; Sun, Shui

    2016-01-01

    The present study aimed to investigate the effect of different concentrations of acetylsalicylic acid combined with diclofenac on the articular cartilage of a rabbit model of osteoarthritis (OA). A total of 40 New Zealand white rabbits were divided into 5 groups. Group A was a sham-operated control group, which was treated with normal saline. Groups B-E were OA models and were treated with normal saline and acetylsalicylic acid combined with diclofenac at concentrations of 5, 10 and 20 mg/kg, respectively. A cartilage macroscopic examination and a pathological observation were performed to analyze the structure of the articular cartilage in all of the treated groups. The nitric oxide (NO) content and interleukin 1β (IL-1β) levels were detected by an enzyme-linked immunosorbent assay. In addition, the protein expression of matrix metalloproteinase 3 (MMP)-3 and MMP-13 were detected by western blot analysis. The mRNA expression of tissue inhibitor of metalloproteinases 1 (TIMP1) was detected by polymerase chain reaction (PCR). The results revealed that different concentrations of the drugs significantly reduced the scores of cartilago articularis, the NO and IL-1β levels and the protein expression of MMP-3 and MMP-13. Furthermore, PCR revealed that the mRNA expression of TIMP1 was significantly upregulated, and the effects increased with increasing drug concentration. Thus, the administration of different concentrations of acetylsalicylic acid combined with diclofenac demonstrates preventive or therapeutic effects against OA progression. PMID:27698707

  11. Effects of immunomodulators on liquefaction and ulceration in the rabbit skin model of tuberculosis.

    PubMed

    Sun, Hongjia; Ma, Xingming; Zhang, Guoping; Luo, Yanping; Tang, Kefeng; Lin, Xiaofa; Yu, Hongjuan; Zhang, Ying; Zhu, Bingdong

    2012-07-01

    To better control tuberculosis (TB) epidemics in developing countries a real need exists to study the liquefaction and cavity formation that occur in pulmonary TB lesions. This report is the first to evaluate the effects of immunomodulators on these two processes in a rabbit skin model. The effects of recombinant human interferon-γ (rIFN-γ), recombinant human interleukin-2 (rIL-2), dexamethasone and cyclophosphamide (CTX) were evaluated in TB lesions produced by intradermal injection of 5 × 10(6) viable BCG bacilli. Recombinant IL-2 and rIFN-γ accelerated the liquefaction and healing of the lesions, and reduced the bacterial load. In contrast, dexamethasone inhibited the liquefaction of the lesions, and increased the bacterial load. The effect of CTX was similar to dexamethasone but not as pronounced. Serum levels of IL-2 were higher during the liquefaction and healing phases in the rIL-2 and rIFN-γ groups. Therefore, immunomodulators affect both the development of TB lesions and the survival of the mycobacteria within them. This study suggests that the rabbit skin model can be a valuable method to select therapeutic agents that could inhibit liquefaction and cavity formation in pulmonary tuberculosis.

  12. The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

    PubMed

    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.

  13. Hepatic Overexpression of GRP94 in a Rabbit Model of Parenteral Nutrition-Associated Liver Disease

    PubMed Central

    Zhu, Xueping; Zhang, Xiaomin; Yu, Lingling; Xu, Yumin; Feng, Xing; Wang, Jian

    2015-01-01

    Objective. To use a rabbit model of parenteral nutrition-associated liver disease (PNALD) to study changes of the endoplasmic reticulum stress (ERS) marker glucose regulatory protein 94 (GRP94) and determine its role in the pathogenesis of PNALD. Methods. A rabbit PNALD model total parenteral nutrition (TPN) group was established. A corresponding control group received breast-feeding for one week. Serum biochemical parameters were measured and liver histological examinations were performed. The level of GRP94 mRNA and protein were measured. Results. The results showed that the serum TBIL, DBIL, and γ-GT levels in the TPN group were significantly higher than those in the control group, while levels of serum ALB in TPN group were significantly lower than those in the control group. The immunohistochemistry results showed that the protein expression level of GRP94 in the liver of TPN group was significantly increased compared with the control group. The RT-PCR results showed that the level of GRP94 mRNA in the liver of the TPN group was significantly higher compared with the control group. Conclusions. The mRNA and protein levels of GRP94 in the TPN group were both significantly increased, indicating that ERS may be directly related to the occurrence and development of PNALD. PMID:25918521

  14. 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

  15. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

    When filling prescriptions for a rabbit, it is important to know whether the rabbit is a pet or is being raised as a source of food for human consumption. Several drugs widely used for pet rabbits are prohibited from exralabel use in animals raised for food production. The list of banned drugs should always be perused prior to filling a prescription for a rabbit being raised for food production. Since no veterinary-approved products exist for rabbits and most medications must be compounded, pharmacists are likely to encounter prescriptions for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy and common diseases will assist pharmacists in distinguishing between safe and dangerous drugs for administration to rabbits.

  16. 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

  17. 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

  18. Aminophylline treatment in meconium-induced acute lung injury in a rabbit model.

    PubMed

    Mokra, D; Mokry, J; Tatarkova, Z; Redfors, B; Petraskova, M; Calkovska, A

    2007-11-01

    Administration of methylxanthines may diminish meconium-induced acute lung injury. Meconium-instilled rabbits intravenously received aminophylline (2.0 mg/kg) at two doses 0.5 h and 2.5 h after meconium instillation or were left without treatment, and were oxygen-ventilated for additional 5 h. At the end of experiment, lungs and trachea were excised. Within 5 h after the first dose of treatment, aminophylline significantly improved gas exchange and decreased right-to-left pulmonary shunts, central venous pressure, and ventilatory pressures. Moreover, aminophylline reduced meconium-induced lung edema formation, airway hyperreactivity to histamine, count of neutrophils in bronchoalveolar lavage fluid associated with higher total white blood cells and neutrophils in the blood, and diminished oxidative modifications of proteins and lipids in lung tissue compared with the non-treated meconium-instilled group. In a rabbit model of the meconium aspiration syndrome, aminophylline treatment enhanced pulmonary functions and alleviated oxidative injury and changes in airway reactivity related to lung inflammation.

  19. 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.

  20. Kinetics of early cholera infection in the removable intestinal tie-adult rabbit diarrhea model.

    PubMed Central

    Spira, W M; Sack, R B

    1982-01-01

    The colonization of the small intestine of adult rabbits challenged with 5 X 10(7) cells of Vibrio cholerae strain Ogawa 395 has been examined in the removable intestinal tie-adult rabbit diarrhea (RITARD) model. During the first 6 h of infection, numbers of both free and adherent vibrios increased at a rate representing a generation time of about 71 min. Detectable fluid output in response to infection began at about 4 to 5 h postchallenge, and overt diarrhea was observed as early as 11 h. By 8 h after challenge, adherent V. cholerae reached a saturation concentration on the intestinal epithelium of approximately 5 X 10(8) cells per g of intestine, whereas numbers of free cells continued to increase at an exponential rate for at least 12 to 14 h. The concentration of adherent cells remained relatively constant at the saturation level during this period. This saturation level was similar in all parts of the small intestine. The concentration of adherent organisms increased significantly in moribund animals, suggesting that factors responsible for the earlier saturation equilibrium began changing as animals neared death. PMID:7068225

  1. 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.

  2. 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.

  3. In vivo bone tunnel evaluation of nanoparticle-grafts using an ACL reconstruction rabbit model.

    PubMed

    Grant, Sheila A; Smith, Sarah E; Schmidt, Hilary; Pfeiffer, Ferris; Kuroki, Kei; Sherman, Seth; White, Richard; Grant, David A

    2017-04-01

    Acellular human gracilis tendons conjugated with gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) were used as a graft in an anterior cruciate ligament (ACL) reconstruction rabbit model. The ACLs of 11 New Zealand rabbits were reconstructed using grafts conjugated without nanoparticles, with AuNP only, and with both AuNP and nano-HAp. Semi-quantitative histological scoring of bone tunnel portion of grafts was performed after 14 weeks. Bone tunnels were scored for graft degeneration, graft remodeling, percentage of new host fibrous connective, collateral connection, head-to-head connection, graft collagen fiber organization, new host fibrous connective tissue organization, and graft and interface vascularity. All grafts were intact at 14 weeks. Results of bone tunnel scoring indicate remodeling in all graft types with new organized host fibrous connective tissue, head-to-head connection to bone and mild inflammation associated with remodeling. Components of the 20 nm AuNP grafts have significantly more graft degeneration, more new host fibrous connective tissue, and more vascularity compared to crosslinked grafts. Comparison between femoral and tibial tunnel scores indicate more degeneration in femoral tunnels compared to tibial tunnels. Overall results indicated potentially enhanced remodeling from the use of 20 nm AuNP grafts. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1071-1082, 2017.

  4. 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

  5. Effect of mitomycin C on the tensile properties of the upper lacrimal canaliculi in a rabbit model.

    PubMed

    Lee, Jeong Kyu; Lee, Moo Yeol; Kim, Mi Kyung; Moon, Nam Ju

    2012-09-01

    The upper lacrimal canaliculus consists of a tubular structure, and the tensile properties which in lacrimal tissues might contribute to structural integrity and tear drainage. We evaluated the characteristics of the tensile properties of the upper lacrimal canaliculi and the clinical implications of using a mitomycin C (MMC)-treated rabbit model. Mitomycin C (0.04%) was applied to the punctum of rabbits for 5 min, and the upper lacrimal tissues including the punctum were excised and attached to a forced transducer to record the tensile properties in a resting state 1 month later. The recording showed continuing decrement of basal tension with time in the lacrimal tissues treated with MMC in contrast with normal controls which maintained initial tension throughout the experiment. The rabbits were then randomly divided into the following 3 groups: vertical punctal incision with the MMC application group; vertical punctal incision with a balanced salt solution application group; and a balanced salt solution application only group. Four weeks after surgery, the puncta of rabbits treated with an incision and MMC application were more dilated clinically and showed less elasticity as compared with the other groups. Histological staining revealed that MMC treatment combined with incision decreased the amount of collagen and elastin fibers in the canaliculi. These results suggest that lacrimal canaliculi of rabbits have rheological basal tension and elasticity, which can be decreased by the use of MMC treatment.

  6. Experimentally infected human body lice (pediculus humanus humanus) as vectors of Rickettsia rickettsii and Rickettsia conorii in a rabbit model.

    PubMed

    Houhamdi, Linda; Raoult, Didier

    2006-04-01

    The human body louse, the natural vector of Rickettsia prowazekii, is able to experimentally transmit the normally flea-borne rickettsia R. typhi, suggesting that the relationships between the body louse and rickettsiae are not specific. We used our experimental infection model to test the ability of body lice to transmit two prevalent tick-borne rickettsiae. Each of two rabbits was made bacteremic by injecting intravenously 2 x 10(6) plaque-forming units of either R. rickettsii or R. conorii. Four hundred body lice were infected by feeding on the bacteremic rabbit and were compared with 400 uninfected lice. Each louse group was fed once a day on a separate seronegative rabbit. The survival of infected lice was not different from that of uninfected controls. Lice remained infected for their lifespan, excreted R. rickettsii and R. conorii in their feces, but did not transmit the infection to their progeny. The nurse rabbit of uninfected lice remained asymptomatic and seronegative. Those rabbits used to feed infected lice developed bacteremia and seroconverted. Although the body louse is not a known vector of spotted fevers, it was able in our study to acquire, maintain, and transmit both R. rickettsii and R. conorii.

  7. 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.

  8. 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.

  9. 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

  10. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model

    PubMed Central

    Haines, Robyn A.; Urbiztondo, Rebeccah A.; Haynes, Rashade A. H.; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D.

    2016-01-01

    Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. PMID:27034393

  11. Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

    PubMed Central

    Park, S J; Oh, J; Kim, Y-K; Park, J H; Park, J Y; Hong, H K; Park, K H; Lee, J-E; Kim, H M; Chung, J Y; Woo, S J

    2015-01-01

    Purpose To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model. Methods VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at −80 °C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties. Results Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively. Conclusion The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied. PMID:25592118

  12. 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

  13. Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

    PubMed Central

    Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

  14. Cardioprotective Effects of Remifentanil in a Sympathetic Hyperactivity Model in Rabbits

    PubMed Central

    Bayındır, Selen; Gökmen, Necati; Erbayraktar, Serhat; Küçükgüçlü, Semih; Yılmaz, Osman; Şahin, Ömer; Öçmen, Elvan; Erdost, Hale Aksu; Sağıroğlu, Emel

    2015-01-01

    Objective In this study, the antiarrhythmic and anti-ischemic effects of a 6 μg kg−1 min−1 infusion dose of remifentanil are investigated in a central sympathetic hyperactivity model in rabbits. Methods In this study, 18 New Zealand rabbits were used. The subjects were randomly divided into three groups (n=6) and received 10 μmol L−1 glutamate intracerebroventricularly to provide the central sympathetic hyperactivity. In group 1, 10 μmol L−1 glutamate was used; in group 2, 1 h before L-glutamate injection, 40 mg kg−1 N (omega)-nitro-L-arginine methyl ester was intravenously (iv) administered; and in group 3, also 1 h before L-glutamate injection, 40 mg kg−1 N (omega)-nitro-L-arginine methyl ester was iv administered. A 6 μg kg−1 min−1 dose of remifentanil infusion was administered 5 min before L-glutamate injection. Heart rate, systolic arterial pressure and mean arterial pressure were measured and recorded. Within 15 min of the intracerebroventricular L-glutamate injection, premature ventricular complexes, bigeminy ventricular arrhythmia, ventricular tachycardia, ST-segment shift and T-wave inversions were recorded. Results When incidences of heart rate, rate pressure product, premature ventricular complexes and bigeminy ventricular arrhythmia were compared between groups, significant differences were not determined. Mean arterial pressure was more significantly increased in group 2 than in the other groups (p<0.05). Ventricular tachycardia, ST-segment shift and T-wave inversions were significantly lower in group 3 than in groups 1 and 2 (p<0.05). Conclusion Remifentanil (6 μg kg−1 min−1 for 5 min of infusion) prevented life-threatening ventricular tachycardia and electrocardiographic signs of myocardial ischemia in a model of arrhythmia resulting from the association of central sympathetic overactivity. PMID:27366503

  15. 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.

  16. Persistent bacteremia in rabbit fetuses despite maternal antibiotic therapy in a novel intrauterine-infection model.

    PubMed

    Gras-Le Guen, C; Debillon, T; Toquet, C; Jarry, A; Winer, N; Jacqueline, C; Kergueris, M F; Bingen, E; Roze, J C; Potel, G; Bugnon, D

    2003-07-01

    The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected chi(2), P < 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 +/- 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 +/- 0.7 log CFU/ml at the start of treatment and 6.2 +/- 0.4 and 5.2 +/- 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means +/- standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbit E. coli maternofetal infection

  17. Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model.

    PubMed

    Dotan, Assaf; Kremer, Israel; Gal-Or, Orly; Livnat, Tami; Zigler, Arie; Bourla, Dan; Weinberger, Dov

    2016-04-03

    Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal abnormalities. In addition, pathological myopia is a common irreversible cause of visual impairment and blindness. Our study demonstrates the effect of scleral crosslinking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. The axial length of the eyeball was measured by A-scan ultrasound in New Zealand white rabbits aged 13 days (male and female). The eye then underwent 360° conjunctival peritomy with scleral crosslinking, followed by tarsorrhaphy. Axial elongation was induced in 13 day-old New Zealand rabbits by suturing their right eye eyelids (tarsorrhaphy). The eyes were divided into quadrants, and every quadrant had two scleral irradiation zones, each with an area of 0.2 cm² and a radius of 4 mm. Crosslinking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones 20 sec before ultraviolet-A irradiation and every 20 sec during the 200 sec irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm² (total UVA light dose, 57 J/cm²). Tarsorrhaphies were removed on day 55, followed by repeated axial length measurements. This study demonstrates that scleral crosslinking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model.

  18. 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

  19. Pseudomonas aeruginosa Infectious Keratitis in a High Oxygen Transmissible Rigid Contact Lens Rabbit Model

    PubMed Central

    Wei, Cynthia; Zhu, Meifang; Petroll, W. Matthew; Robertson, Danielle M.

    2014-01-01

    Purpose. To establish a rabbit model of infectious Pseudomonas aeruginosa keratitis using ultrahigh oxygen transmissible rigid lenses and characterize the frequency and severity of infection when compared to a non–oxygen transmissible lens material. Methods. Rabbits were fit with rigid lenses composed of ultrahigh and non–oxygen transmissible materials. Prior to wear, lenses were inoculated with an invasive corneal isolate of P. aeruginosa stably conjugated to green fluorescent protein (GFP). Corneas were examined before and after lens wear using a modified Heidelberg Rostock Tomograph in vivo confocal microscope. Viable bacteria adherent to unworn and worn lenses were assessed by standard plate counts. The presence of P. aeruginosa-GFP and myeloperoxidase-labeled neutrophils in infected corneal tissue was evaluated using laser scanning confocal microscopy. Results. The frequency and severity of infectious keratitis was significantly greater with inoculated ultrahigh oxygen transmissible lenses. Infection severity was associated with increasing neutrophil infiltration and in severe cases, corneal melting. In vivo confocal microscopic analysis of control corneas following lens wear confirmed that hypoxic lens wear was associated with mechanical surface damage, whereas no ocular surface damage was evident in the high-oxygen lens group. Conclusions. These data indicate that in the absence of adequate tear clearance, the presence of P. aeruginosa trapped under the lens overrides the protective effects of oxygen on surface epithelial cells. These findings also suggest that alternative pathophysiological mechanisms exist whereby changes under the lens in the absence of frank hypoxic damage result in P. aeruginosa infection in the otherwise healthy corneal epithelium. PMID:25125601

  20. 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

  1. Mathematical Models of Atrial and Ventricular Myocytes from the Rabbit Heart

    NASA Astrophysics Data System (ADS)

    Murphey, Carey Richard

    Mathematical models of rabbit atrial and ventricular myocytes that are based on quantitative voltage clamp data from emzymatically isolated cardiac myocytes have been developed. These models are capable of accurately simulating the transmembrane ionic currents recorded in response to a step change in membrane potential (whole-cell voltage clamp response), the nonpropagated membrane action potential (MAP), and the frequency-dependent action potential waveshape changes occurring in response to variations in rate of stimulation. Rectangular pulse, ramp and action potential voltage -clamp measurements of the transmembrane ionic currents have allowed us to model a number of processes thought to be important during repolarization. These computations provide important biophysical insights into the electrophysiological activity of atrial and ventricular cells and their associated intra- and extracellular ionic concentration changes. The present model also has useful predictive capabilities. We have used the model to: (1) estimate the intracellular Ca^{2+} transient in these myocytes and to compare the relative occupancy of the Ca^{2+} binding sites in the contractile proteins with known cellular mechanical activity, and (2) predict the response of the atrial cell to potassium current blockade via BaCl_2 to the bathing medium.

  2. 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

  3. Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model.

    PubMed

    Tang, Cheng; Wang, Feng; Hou, Yanjie; Lu, Shanshan; Tian, Wei; Xu, Yan; Jin, Chengzhe; Wang, Liming

    2015-05-01

    Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome. In this study, we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection. Right knee arthroplasty was performed on 24 New Zealand rabbits. After surgery, methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection (the infected group, n = 12). Rabbits in the control group were injected with sterile saline (n = 12). Seven and 21 days after surgery, technetium-99m-labeled annexin V imaging was performed in 6 rabbits of each group. Images were acquired 1 and 4 hours after injection of technetium-99m-labeled annexin V (150 MBq). The operated-to-normal-knee activity ratios were calculated for quantitative analysis. Seven days after surgery, increased technetium-99m-labeled annexin V uptake was observed in all cases. However, at 21 days a notable decrease was found in the control group, but not in the infected group. The operated-to-normal-knee activity ratios of the infected group were 1.84 ± 0.29 in the early phase and 2.19 ± 0.34 in the delay phase, both of which were significantly higher than those of the control group (P = 0.03 and P = 0.02). The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator, with an accuracy of 80%. In conclusion, technetium-99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.

  4. The effect of paclitaxel-eluting covered metal stents versus covered metal stents in a rabbit esophageal squamous carcinoma model

    PubMed Central

    Zhang, Yin; Ma, Limei; Huang, Jin; Shuang, Jinquan

    2017-01-01

    Background The use of self-expanding metallic stents (SEMSs) is the current treatment of choice for malignant gastrointestinal obstructions. However, these stents can promote only drainage and have no antitumor effect. Some studies have reported that drug-eluting SEMSs may have tumor inhibition potential. The aim of this study was to evaluate the efficiency and safety of paclitaxel-eluting SEMSs (PEMSs) in rabbit esophageal cancer models. Materials and methods A PEMS was covered with a paclitaxel-incorporated membrane, in which the concentration of paclitaxel was 10% (wt/vol). The rabbit models were created endoscopically. Then, a PEMS or SEMS was endoscopically inserted into the rabbit esophagus. Two weeks after stent placement, the rabbits were sacrificed, and we evaluated the tumor volume, area of the wall defect, area of the tumor under endoscopic ultrasound (EUS) before and after stent placement, status of the proximal esophageal obstruction, tumor metastasis food-intake and weight loss. Results A total of 26 rabbits received stent insertion and survived until sacrifice, and migration occurred in 4 cases, 3 in SEMS group and 1 in PEMS group. For the remaining 22 rabbits, at the sacrificed time, the average tumor volume was 7.00±4.30 cm3 in the SEMS group and 0.94±1.51 cm3 in the PEMS group (P<0.05). The area of the esophageal wall defect was 0.70±0.63 cm2 in the SEMS group and 0.17±0.16 cm2 in the PEMS group (P<0.05). The tumor area under EUS was 4.40±1.47 cm2 in the SEMS group and 1.30±1.06 cm2 in the PEMS group (P<0.05). At the time of stent placement, tumor area under EUS was comparable in the two groups. Other indices did not significantly differ between the two groups. Conclusions SEMS and PEMS are both safe and effective to relieve dysphagia in rabbit esophageal cancer models. A PEMS can serve as an alternative tool for advanced esophageal cancer that may inhibit tumor growth by serving as a drug sustained-release platform. Clinical trials of the

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

    PubMed Central

    Chandra, Jyotsna; Long, Lisa; Mukherjee, Pranab K

    2011-01-01

    Most cases of catheter-related bloodstream infections (CRBSIs) involve colonization of microorganisms 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 d. 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

  6. 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

    2016-01-19

    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.

  7. 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

  8. 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

  9. 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.

  10. Validation of a finite element model of a unilateral external fixator in a rabbit tibia defect model.

    PubMed

    Karunratanakul, Kavin; Kerckhofs, Greet; Lammens, Johan; Vanlauwe, Johan; Schrooten, Jan; Van Oosterwyck, Hans

    2013-07-01

    In case of large segmental defects in load-bearing bones, an external fixator is used to provide mechanical stability to the defect site. The overall stiffness of the bone-fixator system is determined not only by the fixator design but also by the way the fixator is mounted to the bone. This stiffness is an important factor as it will influence the biomechanical environment to which tissue engineering scaffolds and regenerating tissues are exposed. A finite element (FE) model can be used to predict the system stiffness. The goal of this study is to develop and validate a 3D anatomical FE model of a bone-fixator system which includes a previously developed unilateral external fixator for a large segmental defect model in the rabbit tibia. It was hypothesized that the contact interfaces between bone and fixator screws play a major role for the prediction of the stiffness. In vitro mechanical testing was performed in order to measure the axial stiffness of cortical bone from mid-shaft rabbit tibiae and of the tibia-fixator system, as well as the bending stiffness of individual fixator screws, inserted in bone. μCT-based case-specific FE models of cortical bone and SCREW-BONE specimens were created to simulate the corresponding mechanical test set-ups. The Young's modulus of rabbit cortical bone as well as appropriate screw-bone contact settings were derived from those FE models. We then used the derived settings in an FE model of the tibia-fixator system. The difference between the FE predicted and measured axial stiffness of the tibia-fixator system was reduced from 117.93% to 7.85% by applying appropriate screw-bone contact settings. In conclusion, this study shows the importance of screw-bone contact settings for an accurate fixator stiffness prediction. The validated FE model can further be used as a tool for virtual mechanical testing in the design phase of new tissue engineering scaffolds and/or novel patient-specific external fixation devices.

  11. 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.

  12. Modeling of transfer kinetics at the serum-cerebrospinal fluid barrier in rabbits with experimental meningitis: application to grepafloxacin.

    PubMed

    Pfister, Marc; Zhang, Liping; Hammarlund-Udenaes, Margareta; Sheiner, Lewis B; Gerber, Cynthia M; Täuber, Martin G; Cottagnoud, Philippe

    2003-01-01

    The goals of the present study were to model the population kinetics of in vivo influx and efflux processes of grepafloxacin at the serum-cerebrospinal fluid (CSF) barrier and to propose a simulation-based approach to optimize the design of dose-finding trials in the meningitis rabbit model. Twenty-nine rabbits with pneumococcal meningitis receiving grepafloxacin at 15 mg/kg of body weight (intravenous administration at 0 h), 30 mg/kg (at 0 h), or 50 mg/kg twice (at 0 and 4 h) were studied. A three-compartment population pharmacokinetic model was fit to the data with the program NONMEM (Nonlinear Mixed Effects Modeling). Passive diffusion clearance (CL(diff)) and active efflux clearance (CL(active)) are transfer kinetic modeling parameters. Influx clearance is assumed to be equal to CL(diff), and efflux clearance is the sum of CL(diff), CL(active), and bulk flow clearance (CL(bulk)). The average influx clearance for the population was 0.0055 ml/min (interindividual variability, 17%). Passive diffusion clearance was greater in rabbits receiving grepafloxacin at 15 mg/kg than in those treated with higher doses (0.0088 versus 0.0034 ml/min). Assuming a CL(bulk) of 0.01 ml/min, CL(active) was estimated to be 0.017 ml/min (11%), and clearance by total efflux was estimated to be 0.032 ml/min. The population kinetic model allows not only to quantify in vivo efflux and influx mechanisms at the serum-CSF barrier but also to analyze the effects of different dose regimens on transfer kinetic parameters in the rabbit meningitis model. The modeling-based approach also provides a tool for the simulation and prediction of various outcomes in which researchers might be interested, which is of great potential in designing dose-finding trials.

  13. Inhibitory Effects of Platelet-Rich Plasma on Intervertebral Disc Degeneration: A Preclinical Study in a Rabbit Model

    PubMed Central

    Gui, Keke; Ren, Weimin; Yu, Yonglin; Li, Xin; Dong, Jiachun; Yin, Wangping

    2015-01-01

    Background Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). Material/Methods Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson’s trichrome, and Safranin O staining, and type II collagen immunohistochemistry. Results Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. Conclusions Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits. PMID:25965093

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

    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.

  16. Histological aspects of the small intestine under variable feed restriction: The effects of short and intense restriction on a growing rabbit model.

    PubMed

    Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Vodicka, Pavel

    2014-11-01

    The objective of this study was to investigate the effect of seven days of feed restriction (between days 42 and 49) on the morphology of the small intestine in experimental rabbit models. Sixty weaned Hyplus rabbits (35 days old) were included in the experiment and split into three groups of 20 rabbits. The first control group (n=20) received feed ad libitum (ADL group), the second (R1) experimental group (n=20) was fed 50 g feed per rabbit per day and the third (R2) experimental group (n=20) received 65 g feed per rabbit per day. Duodenal samples were collected when the rabbits were aged 49, 56, 63 and 70 days. The mean villus height, crypt depth and small intestine length were measured. Significant interactions (P<0.001) between group and age were identified in the villi height and crypt depths. The maximum mean villus height was found in the R2 group in 56-day-old rabbits (643.14 μm), while the minimum was found in the ADL group in 49-day-old rabbits (460.29 μm). The longest (P<0.001) small intestine was measured in the R1 group in 63-day-old rabbits (347.60 cm), while the shortest was measured in the ADL group in 49-day-old rabbits (263.60 cm). The models show that villus height, crypt depth and the length of the small intestine change with the intensity of feed restriction and age.

  17. 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

  18. Bifurcation analysis of oscillating network model of pattern recognition in the rabbit olfactory bulb

    NASA Astrophysics Data System (ADS)

    Baird, Bill

    1986-08-01

    A neural network model describing pattern recognition in the rabbit olfactory bulb is analysed to explain the changes in neural activity observed experimentally during classical Pavlovian conditioning. EEG activity recorded from an 8×8 arry of 64 electrodes directly on the surface on the bulb shows distinct spatial patterns of oscillation that correspond to the animal's recognition of different conditioned odors and change with conditioning to new odors. The model may be considered a variant of Hopfield's model of continuous analog neural dynamics. Excitatory and inhibitory cell types in the bulb and the anatomical architecture of their connection requires a nonsymmetric coupling matrix. As the mean input level rises during each breath of the animal, the system bifurcates from homogenous equilibrium to a spatially patterned oscillation. The theory of multiple Hopf bifurcations is employed to find coupled equations for the amplitudes of these unstable oscillatory modes independent of frequency. This allows a view of stored periodic attractors as fixed points of a gradient vector field and thereby recovers the more familiar dynamical systems picture of associative memory.

  19. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release

    PubMed Central

    Barlow, J. D.; Morrey, M. E.; Hartzler, R. U.; Arsoy, D.; Riester, S.; van Wijnen, A. J.; Morrey, B. F.; Sanchez-Sotelo, J.

    2016-01-01

    Aims Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. DOI: 10.1302/2046-3758.51.2000593 PMID:26813567

  20. Endophthalmitis Prophylaxis Using a Single Drop of Thermoresponsive Controlled-Release Microspheres Loaded with Moxifloxacin in a Rabbit Model

    PubMed Central

    Mammen, Alex; Romanowski, Eric G.; Fedorchak, Morgan V.; Dhaliwal, Deepinder K.; Shanks, R. M.; Kowalski, Regis P.

    2016-01-01

    Purpose Postsurgical endophthalmitis is a sight-threatening problem. We introduce a simple approach by using a single application of thermoresponsive controlled-release microspheres, loaded with moxifloxacin, to prevent bacterial endophthalmitis in a rabbit endophthalmitis prevention model. Methods We separated 24 rabbits into 3 treatment groups in which topical drop treatment was placed onto the conjunctival cul-de-sac: (1) a single drop of controlled-release microspheres containing moxifloxacin, (2) a single drop of controlled-release microspheres without moxifloxacin, and (3) multiple topical treatment with moxifloxacin alone every 15 minutes for 1 hour. All rabbits were challenged, 1 hour after microspheres drop placement and immediately after the fifth topical dose of moxifloxacin, with anterior chamber injections of Staphylococcus aureus. Rabbits in the topical moxifloxacin group also were treated after challenge and four additional times over the next 24 hours. After 24 hours, the rabbits were clinically evaluated for endophthalmitis and the animals were euthanized to culture for intraocular S. aureus. The treatment groups were compared statistically for bacterial endophthalmitis. Results No eyes had endophthalmitis, based on clinical presentation and/or positive culture, in the groups with controlled-release microspheres loaded with moxifloxacin (0/8, 0%) or multiple drops of topical moxifloxacin (0/8, 0%). In contrast, 8 of 8 eyes (100%; P = 0.0001), had endophthalmitis among eyes treated with controlled-release microspheres drops without moxifloxacin. Conclusion A single drop of controlled-release microspheres loaded with moxifloxacin was successful in preventing endophthalmitis. Further clinical studies will be required to confirm the full potential of controlled-release anti-infective loaded microspheres to prevent endophthalmitis. Translational Relevance This study presents a simple method of prophylaxis to prevent postsurgical endophthalmitis. PMID

  1. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.

  2. Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

    PubMed Central

    2014-01-01

    Background The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Results Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. Conclusions The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be

  3. 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.

  4. Growth and shape modelling of the rabbit tibia: study of the dynamics of developing skeleton.

    PubMed

    Pazzaglia, U E; Zarattini, G; Spagnuolo, F; Superti, G; Marchese, M

    2012-06-01

    The proliferative impulse of the growth plate cartilage and related structures and its effect on the dimensions of long bones are well documented. The modulation of shape, however, is less known, and in general, it is referred to the coupled resorption/apposition process of bone modelling. A morphometric study was carried out on rabbit tibiae comparing size increments and shape changes in relation to age. Utilizing measurements made using dried bones, radiography and computerized tomography, it was possible to perform a three-dimensional analysis of shape modulation occurring during a period of growth extending from 3 months to 1 year of age. The dynamics of the shape changes related to growth were studied with a fluorescent tetracycline labelling. This enabled correlation of shape modulation with the 3-D distribution of apposition and resorption. The current thinking behind the influences and mechanical forces affecting bone architecture was discussed in the light of these findings. Several factors play a role in the structural organization of the human and upper vertebrates' skeleton, whose shape is genetically determined in the complex process usually referred as 'modelling'. This does not conflict with the existing evidence of remodelling being influenced by mechanical stimuli, but the unsolved question remains how physical forces (strains) act on the biological substrate of cartilage and bone cells.

  5. The therapy with ethosomes containing 5-fluorouracil for laryngotracheal stenosis in rabbit models.

    PubMed

    Mao, Xiaohui; Cheng, Xuefeng; Zhang, Zheng; Wang, Zhaoyan; Wang, Zhentao

    2016-12-21

    The aim of this study is to evaluate the efficacy of ethosomes encapsulated with 5-fluorouracil (5-FU) in treatment of laryngotracheal stenosis in rabbit models. The 5-FU ethosome was prepared by the thin film hydration method, and the amorphous, size distribution and the encapsulation efficiency was investigated. The tracheal mucosa were scraped about 0.5 cm with a nylon brush to induce the scar in airway grow, then models were divided into three groups: 5-FU ethosome group, 5-FU group and saline group, drug were injected into scar of every group by paracentesis guided under endoscope, respectively. The stenosis states were observed under laryngo fiberscope immediate, 7, 14 and 21 days after administrated. Airway stenosis of 5-FU ethosome group has no significant difference when compared with 5-FU group at 7 days after administration, but 5-FU ethosome significantly reduced the airway stenosis after 21-day administration when compared with 5-FU group again and has no restenosis during the period under observation. The fact that ethosomes encapsulated with 5-FU were effective for laryngotracheal stenosis suggests that it has potential as a new method for ameliorating airway stenosis originating from granulation tissue.

  6. 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

  7. 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

  8. Thermal Injury Model in the Rabbit Ear with Quantifiable Burn Progression and Hypertrophic Scar.

    PubMed

    Friedrich, Emily E; Niknam-Bienia, Solmaz; Xie, Ping; Jia, Sheng-Xian; Hong, Seok Jong; Mustoe, Thomas A; Galiano, Robert D

    2017-04-01

    Hypertrophic scar is a major clinical outcome of deep-partial thickness to full thickness thermal burn injury. Appropriate animal models are a limitation to burn research due to the lack of, or access to, animal models which address the endpoint of hypertrophic scar. Lower species, such as rodents, heal mainly by contracture, which limits the duration of study. Higher species, such as pigs, heal more similarly to humans, but are associated with high cost, long duration for scar development, challenges in quantifying scar hypertrophy, and poor manageability. Here we present a quantifiable deep-partial thickness burn model in the rabbit ear. Burns were created using a dry-heated brass rod for 10 s and 20 s at 90°C. At the time of eschar excision on day 3, excisional wounds were made on the contralateral ear for comparison. Burn wound progression, in which the wound size expands over time is a major distinction between excisional and thermal injuries, was quantified at 1 h and 3 d after the injuries using calibrated photographs and histology and the size of the wounds was found to be unchanged from the initial wound size at 1 h, but 10% in the 20 s burn wounds at 3 d. A quantifiable hypertrophic scar, measured by histology as the scar elevation index, was present in both 20 s burn wounds and excisional wounds at day 35. ImageJ measurements revealed that the 20 s burn wound scars were 22% larger than the excisional wound scars and the 20 s burn scar area measurements from histology were 26% greater than in the excisional wound scar. The ability to measure both burn progression and scar hypertrophy over a 35-day time frame suits this model to screening early intervention burn wound therapeutics or scar treatments in a burn-specific scar model. This article is protected by copyright. All rights reserved.

  9. 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

  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

  11. Effects of prednisone and ibuprofen on radio frequency volume tissue reduction in a rabbit model.

    PubMed

    Han, Joseph K; Woodson, B Tucker

    2002-11-01

    This study investigates whether acute anti-inflammatory medications (prednisone and ibuprofen) alter muscle volumetric reduction following radio frequency tissue ablation (RFTA). We used a rabbit model to measure changes in leg muscle volume using serial magnetic resonance imaging in 3 groups: RFTA without medication (group 1), RFTA with prednisone and ibuprofen (group 2), and no RFTA or medication (group 3). The mean volumetric changes for groups I and 2 differed on days 1 and 7 (+0.5 cm3 versus -0.4 cm3, p < .0001; and -0.03 cm3 versus -0.7 cm3, p < .05), but not on day 28 (-0.8 cm3 versus -1.0 cm3, not significant). Group 3 had no change in volume. The volumetric reduction varied. Impaired volumetric reduction (<50% mean change) occurred in 30% of extremities and correlated to lower tissue impedance (p < .04). Combined steroidal and nonsteroidal anti-inflammatory medications did decrease acute edema, but not the final volumetric reduction, following RFTA. Volumetric changes are variable and may be altered by tissue impedance.

  12. Tetracycline labeling as an aid to complete excision of partial physeal arrest: a rabbit model.

    PubMed

    Post, W R; Jones, E T

    1992-01-01

    We determined whether ultraviolet (UV) visualization of tetracycline-labeled bone allows more complete excision of experimentally created physeal arrests while minimizing required bone resection. Lateral distal femoral growth arrests were surgically created bilaterally in eight 6-week-old New Zealand white rabbits, given 3 daily oxytetracycline doses (10 mg/kg); the animals were killed 6 weeks postoperatively. Femurs were excised and dissected free of soft tissue. Ten of 16 operated femurs randomized into two groups had consistent deformity. In group I, arrest was excised with a high-speed burr without, and, in group II, with ultraviolet visualization. In group II, metaphyseal bone and calcified arrest glowed brightly, contrasting well with the epiphyseal plate. All excised specimens were examined under x 9 magnification to assess remaining bone bridges. Excision defects were filled with modeling clay, which was then removed and weighed. Thorough excision was confirmed in each specimen. Resection was easier and less bone usually was resected in the UV group (difference not statistically significant). This technique would best be used in resection of arrests involving small physes such as the distal radius, in which maximal visualization and minimal resection are essential to preserve all possible growth potential. Tetracycline labeling and intraoperative UV visualization of fluorescence allows thorough excision of partial physeal arrest while minimizing required bone resection.

  13. Preferential pharmacological inhibition of macrophage ACAT increases plaque formation in mouse and rabbit models of atherogenesis.

    PubMed

    Perrey, S; Legendre, C; Matsuura, A; Guffroy, C; Binet, J; Ohbayashi, S; Tanaka, T; Ortuno, J C; Matsukura, T; Laugel, T; Padovani, P; Bellamy, F; Edgar, A D

    2001-04-01

    The cholesteryl ester, foam cell-enriched vulnerable plaque is a principle pharmacological target for reducing athero-thrombosis. Acyl CoA:cholesterol Acyl Transferase (ACAT) catalyzes the esterification of free cholesterol in intestine, liver, adrenal and macrophages, leading in the latter cells to intracellular cholesteryl ester accumulation and foam cell formation in the arterial intima. Previous studies suggested the existence of several isoforms of ACAT with different tissue distribution and this has largely been confirmed by molecular cloning of ACAT-1 and ACAT-2. We developed a series of ACAT inhibitors that preferentially inhibited macrophage ACAT relative to hepatic or intestinal ACAT based on in vitro assays and ex vivo bioavailability studies. Four of these compounds were tested in three models of atherosclerosis at oral doses shown to give sufficient bioavailable monocyte/macrophage ACAT inhibitory activity. In fat-fed C57BL/6 mice, chow fed apo E-/- mice and KHC rabbits, the various ACAT inhibitors had either no effect or increased indices of atherosclerotic foam cell formation. Direct and indirect measurements suggest that the increase in plaque formation may have been related to inhibition of macrophage ACAT possibly leading to cytotoxic effects due to augmented free cholesterol. These results suggest that pharmacological inhibition of macrophage ACAT may not reduce, but actually aggravate, foam cell formation and progression.

  14. In vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model.

    PubMed

    Stubbs, D; Deakin, M; Chapman-Sheath, P; Bruce, W; Debes, J; Gillies, R M; Walsh, W R

    2004-09-01

    Calcium sulfate as a bone graft substitute is rapidly resorbed in vivo releasing calcium ions but fails to provide long-term three-dimensional framework to support osteoconduction. The setting properties of calcium sulfate however allow it to be applied in a slurry form making it easier to handle and apply in different situations. This study examines the in vivo response of calcium sulfate alone and as a carrier for a coralline hydroxyapatite in an established bilateral corticocancellous defect model in rabbits. Defects were filled flush to the anterior cortex with a resorbable porous ceramic alone and in combination with calcium sulfate slurry, calcium sulfate slurry alone or calcium sulfate pellets and examined at time points up to 52 weeks. Specimens where assessed using Faxitron X-ray, light and electron microscopy. Calcium sulfate in either slurry or pellet form does indeed support new bone formation alone however, complete filling of the bone defect is not observed. Calcium sulfate in slurry form does however improve the surgical handling of particulate bone graft substitutes such as Pro Osteon 200 R, which remained as an osteoconductive scaffold for up to 52 weeks and may have played an important role in the ultimate closure of the cortical windows.

  15. A model for investigating the control of muscle blood flow: the masseteric artery in conscious rabbits.

    PubMed

    Roatta, S; Mohammed, M; Turturici, M; Milano, L; Passatore, M

    2010-09-01

    The complex interplay of neural, metabolic, myogenic and mechanical mechanisms that regulate blood flow in skeletal muscle (MBF) is still incompletely understood. For the first time, a method is presented for high time-resolution recording of MBF from a purely muscular artery in physiological conditions. Ultrasound perivascular flow probes were implanted (n = 15) mono- or bilaterally around the masseteric branch of the facial artery in nine rabbits and tested up to 16 days after implant. Reliable and stable recordings were achieved in 50% of implants. Blood flow was observed to increase from a resting level of 0.2-0.3 ml min(-1) up to 4.0-6.0 ml min(-1) during spontaneous masticatory activity. In addition, within single masticatory cycles marked back flow transients could be observed (peak flow = -10 ml min(-1)) during powerful masticatory strokes but not during mild mastication. The possibility of (1) surgically removing the sympathetic supply to the relevant vascular bed and of (2) bilaterally monitoring the perfusion of masseter muscles thus allowing to use one side as control side for different types of interventions makes this model a useful tool for disentangling the different mechanisms involved in the control of MBF.

  16. 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.

  17. The effects of Rumalon, a glycosaminoglycan peptide complex, in a partial meniscectomy model of osteoarthritis in rabbits.

    PubMed

    Moskowitz, R W; Reese, J H; Young, R G; Fein-Krantz, D; Malemud, C J; Caplan, A I

    1991-02-01

    The effects of Rumalon, a glycosaminoglycan peptide complex (GP-C), were evaluated in a partial meniscectomy model of osteoarthritis (OA). When rabbits were treated with Rumalon, 0.25 ml/kg 3 times/week for 12 weeks after partial meniscectomy, the proportion of animals that developed cartilage ulceration was lower than that in untreated meniscectomized rabbits (p less than 0.05). At 6 weeks sacrifice, the same dose of Rumalon was associated with a trend toward reduction in the number of animals with ulcerations. Rumalon administered at a dose of 0.5 ml/kg for 12 weeks reduced the number of animals with ulcers, although not at the p less than 0.05 level of significance. Semiquantitative histologic evaluations revealed no differences between control and treatment groups either in the thickness of articular cartilage, density of cells present, safranin-O stain or ratio of DNA/protein. Increased proteoglycan synthesis characteristic of OA was modulated toward normal in association with Rumalon therapy. Diminished OA changes in response to Rumalon are consistent with an ameliorative response to this agent in the partial meniscectomy model in the rabbit.

  18. β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model

    PubMed Central

    Negroni, Jorge A.; Morotti, Stefano; Lascano, Elena C.; Gomes, Aldrin V.; Grandi, Eleonora; Puglisi, José L; Bers, Donald M.

    2015-01-01

    A five-state model of myofilament contraction was integrated into a well-established rabbit ventricular myocyte model of ion channels, Ca2+ transporters and kinase signaling to analyze the relative contribution of different phosphorylation targets to the overall mechanical response driven by β-adrenergic stimulation (β-AS). β-AS effect on sarcoplasmic reticulum Ca2+ handling, Ca2+, K+ and Cl− currents, and Na+/K+-ATPase properties were included based on experimental data. The inotropic effect on the myofilaments was represented as reduced myofilament Ca2+ sensitivity (XBCa) and titin stiffness, and increased cross-bridge (XB) cycling rate (XBcy). Assuming independent roles of XBCa and XBcy, the model reproduced experimental β-AS responses on action potentials and Ca2+ transient amplitude and kinetics. It also replicated the behavior of force-Ca2+, release-restretch, length-step, stiffness-frequency and force-velocity relationships, and increased force and shortening in isometric and isotonic twitch contractions. The β-AS effect was then switched off from individual targets to analyze their relative impact on contractility. Preventing β-AS effects on L-type Ca2+ channels or phospholamban limited Ca2+ transients and contractile responses in parallel, while blocking phospholemman and K+ channel (IKs) effects enhanced Ca2+ and inotropy. Removal of β-AS effects from XBCa enhanced contractile force while decreasing peak Ca2+ (due to greater Ca2+ buffering), but had less effect on shortening. Conversely, preventing β-AS effects on XBcy preserved Ca2+ transient effects, but blunted inotropy (both isometric force and especially shortening). Removal of titin effects had little impact on contraction. Finally, exclusion of β-AS from XBCa and XBcy while preserving effects on other targets resulted in preserved peak isometric force response (with slower kinetics) but nearly abolished enhanced shortening. β-AS effects on XBCa vs. XBcy have greater impact on isometric

  19. β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model.

    PubMed

    Negroni, Jorge A; Morotti, Stefano; Lascano, Elena C; Gomes, Aldrin V; Grandi, Eleonora; Puglisi, José L; Bers, Donald M

    2015-04-01

    A five-state model of myofilament contraction was integrated into a well-established rabbit ventricular myocyte model of ion channels, Ca(2+) transporters and kinase signaling to analyze the relative contribution of different phosphorylation targets to the overall mechanical response driven by β-adrenergic stimulation (β-AS). β-AS effect on sarcoplasmic reticulum Ca(2+) handling, Ca(2+), K(+) and Cl(-) currents, and Na(+)/K(+)-ATPase properties was included based on experimental data. The inotropic effect on the myofilaments was represented as reduced myofilament Ca(2+) sensitivity (XBCa) and titin stiffness, and increased cross-bridge (XB) cycling rate (XBcy). Assuming independent roles of XBCa and XBcy, the model reproduced experimental β-AS responses on action potentials and Ca(2+) transient amplitude and kinetics. It also replicated the behavior of force-Ca(2+), release-restretch, length-step, stiffness-frequency and force-velocity relationships, and increased force and shortening in isometric and isotonic twitch contractions. The β-AS effect was then switched off from individual targets to analyze their relative impact on contractility. Preventing β-AS effects on L-type Ca(2+) channels or phospholamban limited Ca(2+) transients and contractile responses in parallel, while blocking phospholemman and K(+) channel (IKs) effects enhanced Ca(2+) and inotropy. Removal of β-AS effects from XBCa enhanced contractile force while decreasing peak Ca(2+) (due to greater Ca(2+) buffering), but had less effect on shortening. Conversely, preventing β-AS effects on XBcy preserved Ca(2+) transient effects, but blunted inotropy (both isometric force and especially shortening). Removal of titin effects had little impact on contraction. Finally, exclusion of β-AS from XBCa and XBcy while preserving effects on other targets resulted in preserved peak isometric force response (with slower kinetics) but nearly abolished enhanced shortening. β-AS effects on XBCa and XBcy

  20. Toxicity and immunogenicity of purified Haemophilus ducreyi cytolethal distending toxin in a rabbit model.

    PubMed

    Wising, Catharina; Svensson, Liselott A; Ahmed, Hinda J; Sundaeus, Vivianne; Ahlman, Karin; Jonsson, Ing-Marie; Mölne, Lena; Lagergård, Teresa

    2002-08-01

    The cytolethal distending toxin of Haemophilus ducreyi (HdCDT) is a three-component toxin that induces the arrest of the mammalian cell cycle in the G2 phase. All of the individual gene products, CdtA, CdtB and CdtC, are required for toxic activity on cultured mammalian cells. The CdtB component alone exerts nuclease activity. The individual HdCDT components were purified by affinity chromatography or ion-exchange chromatography followed by gel-filtration. HdCDT was reconstituted and purified by the immobilization of a GST-CdtB fusion on a GSTrap column and the subsequent addition of cell sonicates from Escherichia coli recombinants that produced CdtA and CdtC. The purified HdCDT preparation contained all three CDT proteins, as detected by immuno-blotting, and had high cytotoxic activity (10(6)CPU/ml). Immunization of rabbits with the HdCDT complex and with the individual CdtA, CdtB and CdtC proteins elicited high titres of antibodies, as detected by ELISA. All of the immune sera had toxin-neutralizing activities. The pathological effects of the HdCDT complex were investigated in rabbits, since the proliferation of two rabbit cell lines, SIRC and RK-13, was inhibited by HdCDT. Intradermal injection of HdCDT (1, 10, 50 and 100microg protein) into naive rabbits resulted in dose-dependent skin reactions (erythema) about 24h after injection. Similar effects were not observed when the individual HdCDT proteins were injected. HdCDT injection into immune rabbits resulted in dose-dependent skin responses that were characterized by both erythema and oedema. Histological evaluation of the 24-h lesions in naive rabbits that were injected with HdCDT, revealed moderate levels of inflammatory cells, which were mainly granulocytes and macrophages, and dilatation of blood vessels. The skin reactions in HdCDT-injected immunized rabbits showed pronounced vascular changes and extensive infiltration of inflammatory cells, including eosinophils. All of the pathological changes healed

  1. The effectiveness of extra-scrotal fixation following manual detorsion for testicular torsion: a pilot study in a rabbit model

    PubMed Central

    Altok, Muammer; Özmen, Özlem; Değirmenci, Bumin; Özyildiz, Zafer; Baş, Ercan; Kara, Mustafa; Kaya, Cevdet

    2016-01-01

    Introduction To investigate the effectiveness of manual detorsion (MD) and applicability of extra-scrotal fixation for testicular torsion in a rabbit model. Material and methods Twelve New Zealand male rabbits were randomized into six groups of two rabbits each. A single-side testicular torsion (TT) model (different degrees, time and sides) was performed in all groups except the Sham group. The groups included: Group 1 (180°; 4 h), Group 2 (720°; 6 h), Group 3 (1080°; 9 h), Group 4 (540°; 1 h), Group 5 (900°; 2 h), and Group 6 (sham-only). Testes were examined by another urologist and radiologist with Color Doppler Ultrasonography (CDU). MD was performed with CDU until blood flow was observed in the affected testis. Extra-scrotal fixation was then conducted in these animals. The testes were then harvested for blinded histopathological examinations. Results TT was detected in all animals except the control group. The CDU examination detected decreased blood flow only in Group 1. An opposite rate was observed between the spermatic cord diameter and torsion degree. A wrong direction of MD in the first step was observed in two rabbits in Groups 4 and 5. Torsion signs were observed only in Group 3. Rest torsion was observed in Groups 3 and 5 after extra-scrotal fixation. Histopathological examinations showed that testicular damage increased in parallel to torsion duration. Conclusions Extra-scrotal fixation after MD along with CDU may be a simple and minimally invasive treatment option in TT therapy. However, this must be verified with further studies. PMID:28127460

  2. Genetics of litter size in three maternal lines of rabbits: repeatability versus multiple-trait models.

    PubMed

    Piles, M; García, M L; Rafel, O; Ramon, J; Baselga, M

    2006-09-01

    Variance components were estimated in 3 lines of rabbits selected for litter size at weaning (A, Prat, and V) to test one of the assumptions of the models used for selection: that litter size data at different parities are repeated measurements of the same trait. Multiple-trait analyses were performed for the total number of kits born (TB), the number of kits born alive (BA), and the number of kits weaned (NW) per litter. Estimates were obtained by REML in multivariate analyses, including all of the information of the selection criteria, under a repeatability model or a multiple-trait model, considering litter size at the first, second, and subsequent parities as different traits. Models included the fixed effects of the physiological status of the female and the year-season of mating day, buck and doe random permanent environmental effects, and doe additive genetic effects. Results indicated that prolificacy was determined mainly by doe components and that the service sire had a very small effect. Heritabilities for the first and second parities were greater than the estimates obtained under the repeatability model (0.04 to 0.14 for the repeatability model). In the A and V lines, similar values of heritability were found at the first and second parities, but in the Prat line heritability at the second parity was always greater than at the first and greater parities (values of 0.21, 0.17, and 0.15 for TB, BA, and NW, respectively, in second parities of the Prat line). Genetic correlations between the same traits at different parities were approximately 0.8 for all traits in line A, but much lower in the other 2 lines. On average, the values were 0.64 for TB, 0.48 for BA, and 0.39 for NW between the first and second parities, and 0.65 for TB, 0.56 for BA, and 0.45 for NW between the first and third and greater parities. Genetic correlations between the second and greater parities showed the greatest values (approximately 0.8) in lines A and Prat for all traits, but

  3. The Immunologic Injury Composite with Balloon Injury Leads to Dyslipidemia: A Robust Rabbit Model of Human Atherosclerosis and Vulnerable Plaque

    PubMed Central

    Zhang, Guangyin; Li, Ming; Li, Liangjun; Xu, Yingzhi; Li, Peng; Yang, Cui; Zhou, Yanan; Zhang, Junping

    2012-01-01

    Atherosclerosis is a condition in which a lipid deposition, thrombus formation, immune cell infiltration, and a chronic inflammatory response, but its systemic study has been hampered by the lack of suitable animal models, especially in herbalism fields. We have tried to perform a perfect animal model that completely replicates the stages of human atherosclerosis. This is the first combined study about the immunologic injury and balloon injury based on the cholesterol diet. In this study, we developed a modified protocol of the white rabbit model that could represent a novel approach to studying human atherosclerosis and vulnerable plaque. PMID:22988422

  4. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

    SciTech Connect

    Zhang, Wen Yan, Zhiping Luo, Jianjun Fang, Zhuting Wu, Linlin Liu, QingXin Qu, Xudong Liu, Lingxiao Wang, Jianhua

    2013-10-15

    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX{sub 2} was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 {+-} 0.12 kg, 57.83 {+-} 8.68 days, (16.73 {+-} 5.18 %), (29.47 {+-} 7.18 %), and 2.03 {+-} 0.13 kg, 43.67 {+-} 5.28 days, (63.01 {+-} 2.01 %), (6.02 {+-} 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT

  5. Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning.

    PubMed Central

    Morrow, N G; Kraus, W E; Moore, J W; Williams, R S; Swain, J L

    1990-01-01

    Increased tonic contractile activity from exercise or electrical stimulation induces a variety of changes in skeletal muscle, including vascular growth, myoblast proliferation, and fast to slow fiber type conversion. Little is known about the cellular control of such changes, but pleiotropic biochemical modulators such as fibroblast growth factors (FGFs) may be involved in this response and thus may be regulated in response to such stimuli. We examined the regulation of FGF expression in an in vivo model of exercise conditioning previously shown to exhibit vascular growth and fast to slow fiber conversion. FGFs were extracted by heparin-affinity chromatography from extensor digitorum longus muscles of adult rabbits subjected to chronic motor nerve stimulation at 10 Hz. Growth factor activity (expressed in growth factor units [GFUs]) of muscle stimulated for 3 and 21 d was assayed by [3H]thymidine incorporation in 3T3 fibroblasts and compared with that present in the contralateral unstimulated muscle. A small increase in heparin-binding mitogenic activity was observed as early as 3 d of stimulation, and by 21 d mitogenic activity increased significantly when normalized to either wet weight (stimulated, 287 +/- 61 GFU/g; unstimulated, 145 +/- 39 GFU/g) or to protein (stimulated, 5.3 +/- 1.1 GFU/mg; unstimulated, 2.2 +/- 0.6 GFU/mg) (+/- SE, P less than 0.05). Western analysis demonstrated increased amounts of peptides with immunological identity to acidic and basic FGFs in stimulated muscle. The increase in FGF content observed in this study is synchronous with neovascularization, myoblast proliferation, and fast to slow fiber type conversion previously shown in this model. These results demonstrate that increased expression of FGFs is associated with motor nerve stimulation and increased tonic contractile activity of skeletal muscle, and suggests that these proteins may play a regulatory role in the cellular changes that occur during exercise conditioning. Images

  6. Implantation of scaffold-free engineered cartilage constructs in a rabbit model for chondral resurfacing.

    PubMed

    Brenner, Jillian M; Ventura, Nicole M; Tse, M Yat; Winterborn, Andrew; Bardana, Davide D; Pang, Stephen C; Hurtig, Mark B; Waldman, Stephen D

    2014-02-01

    Joint resurfacing techniques offer an attractive treatment for damaged or diseased cartilage, as this tissue characteristically displays a limited capacity for self-repair. While tissue-engineered cartilage constructs have shown efficacy in repairing focal cartilage defects in animal models, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of larger defects. In a previous study, we developed a novel approach to generate large, scaffold-free cartilaginous constructs from a small number of donor cells (20 000 cells to generate a 3-cm(2) tissue construct). As comparable thicknesses to native cartilage could be achieved, the purpose of the present study was to assess the ability of these constructs to survive implantation as well as their potential for the repair of critical-sized chondral defects in a rabbit model. Evaluated up to 6 months post-implantation, allogenic constructs survived weight bearing without a loss of implant fixation. Implanted constructs appeared to integrate near-seamlessly with the surrounding native cartilage and also to extensively remodel with increasing time in vivo. By 6 months post-implantation, constructs appeared to adopt both a stratified (zonal) appearance and a biochemical composition similar to native articular cartilage. In addition, constructs that expressed superficial zone markers displayed higher histological scores, suggesting that transcriptional prescreening of constructs prior to implantation may serve as an approach to achieve superior and/or more consistent reparative outcomes. As the results of this initial animal study were encouraging, future studies will be directed toward the repair of chondral defects in more mechanically demanding anatomical locations.

  7. Pesticide deposition in hair: preliminary results of a model study of methomyl incorporation into rabbit hair.

    PubMed

    Tsatsakis, A M; Tutudaki, M I; Tzatzarakis, M N; Psaroudakis, K; Dolapsakis, G P; Michalodimitrakis, M N

    1998-08-01

    This work studied the incorporation of methomyl, a carbamate insecticide, into the hair of New Zealand white rabbits. A total of 600 mg methomyl was administered by drinking water over 4 mo, and acetylcholinesterase activity in serum was monitored. At the end of the dosing period, hair from the back of the rabbits was cut off, and the methomyl concentration was measured using ELISA and HPLC. A decrease of serum acetylcholinesterase occurred. The top cm of hair contained no methomyl, the second cm contained 0.9 ng/mg and the 3rd cm of hair contained 3 ng methomyl/mg. Methomyl was incorporated into the rabbit hair in a process independent of gender but dependent on the hair growth rate.

  8. Magnesium alloy covered stent for treatment of a lateral aneurysm model in rabbit common carotid artery: An in vivo study

    PubMed Central

    Wang, Wu; Wang, Yong-Li; Chen, Mo; Chen, Liang; Zhang, Jian; Li, Yong-Dong; Li, Ming-Hua; Yuan, Guang-Yin

    2016-01-01

    Magnesium alloy covered stents have rarely been used in the common carotid artery (CCA). We evaluated the long-term efficacy of magnesium alloy covered stents in a lateral aneurysm model in rabbit CCA. Magnesium alloy covered stents (group A, n = 7) or Willis covered stents (group B, n = 5) were inserted in 12 New Zealand White rabbits and they were followed up for 12 months. The long-term feasibility for aneurysm occlusion was studied through angiograms; the changes in vessel area and lumen area were assessed with IVUS. Complete aneurysmal occlusion was achieved in all aneurysms. Angiography showed that the diameter of the stented CCA in group A at 6 and 12 months was significantly greater than the diameter immediately after stent placement. On intravascular ultrasound (IVUS) examination, the mean lumen area of the stented CCA in group A was significantly greater at 6 and 12 months than that immediately after stent placement; the mean lumen area was also significantly greater in group A than in group B at the same time points. The magnesium alloy covered stents proved to be an effective approach for occlusion of lateral aneurysm in the rabbit CCA; it provides distinct advantages that are comparable to that obtained with the Willis covered stent. PMID:27869217

  9. Magnesium alloy covered stent for treatment of a lateral aneurysm model in rabbit common carotid artery: An in vivo study

    NASA Astrophysics Data System (ADS)

    Wang, Wu; Wang, Yong-Li; Chen, Mo; Chen, Liang; Zhang, Jian; Li, Yong-Dong; Li, Ming-Hua; Yuan, Guang-Yin

    2016-11-01

    Magnesium alloy covered stents have rarely been used in the common carotid artery (CCA). We evaluated the long-term efficacy of magnesium alloy covered stents in a lateral aneurysm model in rabbit CCA. Magnesium alloy covered stents (group A, n = 7) or Willis covered stents (group B, n = 5) were inserted in 12 New Zealand White rabbits and they were followed up for 12 months. The long-term feasibility for aneurysm occlusion was studied through angiograms; the changes in vessel area and lumen area were assessed with IVUS. Complete aneurysmal occlusion was achieved in all aneurysms. Angiography showed that the diameter of the stented CCA in group A at 6 and 12 months was significantly greater than the diameter immediately after stent placement. On intravascular ultrasound (IVUS) examination, the mean lumen area of the stented CCA in group A was significantly greater at 6 and 12 months than that immediately after stent placement; the mean lumen area was also significantly greater in group A than in group B at the same time points. The magnesium alloy covered stents proved to be an effective approach for occlusion of lateral aneurysm in the rabbit CCA; it provides distinct advantages that are comparable to that obtained with the Willis covered stent.

  10. Study of nano-hydroxyapatite/zirconia stabilized with yttria in bone healing: histopathological study in rabbit model.

    PubMed

    Abedi, Gholamreza; Jahanshahi, Amirali; Fathi, Mohamad Hosein; Haghdost, Iraj Sohrabi; Veshkini, Abas

    2014-03-01

    Acceleration of bone healing has always been a major challenge in orthopedic surgery, the aim of this study was an evaluation of the biological effects of zirconia-stabilized yttria on bone healing, using an in vivo model. Nano-hydroxyapatite powder with zirconia-stabilized yttria were inserted in rabbit tibia and then histologically analyzed and compared with non-treated controls so thirty six. New Zealand white male rabbits randomly divided into two groups of 18 rabbits each. A cortical hole of 4 mm diameter and 8 mm depth in each tibia was drilled. In group I, the defect was left empty, whereas in group II, the bone defect was packed with nano-hydroxyapatite/5% zirconia stabilized with yttria. Histological evaluations were performed at two, four and six weeks after the implantation. Microscopic changes on two groups along with the time course were scored and statistical analysis showed that the average scores in group II were significantly higher than the other groups (p < 0.05). Histological analysis was shown to be significantly improved by the nano-hydroxyapatite/5% zirconia stabilized with yttria compared with the control group, suggesting that this biomaterial promote the healing of cortical bone, presumably by acting as an osteoconductive.

  11. Rabbit knee model of post-traumatic joint contractures: the long-term natural history of motion loss and myofibroblasts.

    PubMed

    Hildebrand, Kevin A; Sutherland, Craig; Zhang, Mei

    2004-03-01

    Our objective is to describe the natural history of motion loss with time and myofibroblast numbers in a rabbit knee model of post-traumatic joint contractures. Twenty-eight skeletally mature New Zealand White female rabbits had five-mm-squares of cortical bone removed from the medial and lateral femoral condyles of the right knee. A Kirschner wire (K-wire) was used to immobilize the knee joint in maximum flexion. A second operation was performed 8 weeks later to remove the K-wire. The rabbits were divided into four groups depending on the time of remobilization; 0, 8, 16 or 32 weeks. The average flexion contracture of the experimental knees in the 0-week and 8-week remobilization groups (38 degrees and 33 degrees, respectively) were significantly greater when compared with the values of the unoperated contralateral knees (8 degrees). The average flexion contractures of the experimental knees in the 16-week and 32-week remobilization groups were also greater than the unoperated contralateral knees, although they were not statistically significant. The average flexion contractures of the 16-week and 32-week groups were 19 degrees and 18 degrees, respectively, indicating a stabilization of the motion loss. Myofibroblast numbers in the posterior joint capsules were elevated 4-5x in the knees with contractures when compared to the contralateral knees. The initial decrease in severity followed by stabilization of motion loss and the association of motion loss with myofibroblasts mimics the human scenario of permanent post-traumatic joint contractures.

  12. Magnetic resonance elastography in a rabbit model of liver fibrosis: a 3-T longitudinal validation for clinical translation

    PubMed Central

    Zou, Liqiu; Jiang, Jinzhao; Zhong, Wenxin; Wang, Chunrong; Xing, Wei; Zhang, Zhuoli

    2016-01-01

    This study aimed to determine the relationships between magnetic resonance elastography (MRE) imaging biomarkers and the stages of liver fibrosis in a rabbit model of liver fibrosis, a longitudinal validation for clinical translation. Liver fibrosis was induced in 38 male New Zealand rabbits by weekly subcutaneous injections of 0.1 ml 50% carbon tetrachloride oily solution per kilogram of body weight for 4 to 10 weeks to produced varying degrees of liver fibrosis. The values for the liver stiffness (LS) MRE imaging biomarkers were measured at different stages of liver fibrosis. Masson trichrome staining of liver tissue was used to identify collagen tissue. Among the 38 rabbits, the histological studies showed liver fibrosis stage 1 (F1, n = 11), liver fibrosis stage 2 (F2, n = 8), liver fibrosis stage 3 (F3, n = 7), and liver fibrosis stage 4 (F4, liver cirrhosis, n = 12). Additional healthy rabbits served as controls (F0, n = 15). During liver fibrosis progression, the mean LS values increased during liver fibrosis progression. There were significant differences in LS values between (F0 and F1) and (F2 and F3), (F2 and F3) and (F4), and (F0 and F1) and (F4), which are three clinically relevant fibrosis groups. There was a high correlation between the LS values measured by MRE and the stages of liver fibrosis determined by histology (R2 = 0.67, P < 0.001). MRE imaging has the potential to serve as a noninvasive, unenhanced imaging technique for liver fibrosis diagnosis and staging. PMID:27904692

  13. Role of Sarcoplasmic Reticulum Calcium in Development of Secondary Calcium Rise and Early Afterdepolarizations in Long QT Syndrome Rabbit Model

    PubMed Central

    Chang, Po-Cheng; Wo, Hung-Ta; Lee, Hui-Ling; Lin, Shien-Fong; Wen, Ming-Shien; Chu, Yen; Yeh, San-Jou; Chou, Chung-Chuan

    2015-01-01

    Background L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs. Objective To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs. Methods Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated. Results At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts. Conclusion In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs. PMID:25875599

  14. The impact of orthopedic device associated with carbonated hydroxyapatite on the oxidative balance: experimental study of bone healing rabbit model.

    PubMed

    Jebahi, Samira; Nsiri, Riadh; Boujbiha, Mohammed; Bouroga, Ezedine; Rebai, Tarek; Keskes, Hassib; El Feki, Abdelfattah; Oudadesse, Hassane; El Feki, Hafed

    2013-10-01

    Orthopedic devices are used in pathologic disorder as an adjunct to bone grafts to provide immediate structural stability. Unfortunately, the use of metallic devices has some complications. This study aimed to characterize the oxidative stress biomarker and the antioxidant enzyme profiles during bone regeneration. New Zealand White rabbits were divided into 4 groups: Group (I) was used as control (T), Groups II, III, and IV were used, respectively, as implanted tissue with carbonated hydroxyapatite (CHA), carbonated hydroxyapatite associated with external fixator (CHA + EF), and presenting empty defects (ED). Grafted bone tissues were carefully removed to measure malondialdehyde (MDA) concentration, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities (GPx). Our results showed that 4 weeks after operation, treatment of rabbits with CHA + EF showed a significantly higher malondialdehyde (MDA) concentration when compared to that of control group. The SOD, CAT, and GPx in CHA + EF group showed significantly lower activities when compared to those in control group. Eight weeks after surgery, the CHA + EF group presented a lower concentration of MDA as compared to those seen after the first 4 weeks after surgery. On the other hand, the SOD, CAT, and GPx showed a higher activity when compared with the same group. Consequently, MDA concentration and the antioxidant enzyme activities were not significant (p > 0.05) when compared to those in control group rabbits. Histologic sampling has demonstrated successful time-patterned resorption accompanied by bone replacement and remodeling. These results suggest that there was a temporary increase in the oxidative marker level in CHA + EF healing bone and the 8-week period was sufficient to re-establish oxidant-antioxidant balance accompanied by bone repair in the tibia rabbit model.

  15. Modelling of the dynamic relationship between arterial pressure, renal sympathetic nerve activity and renal blood flow in conscious rabbits.

    PubMed

    Berger, C S; Malpas, S C

    1998-12-01

    A linear autoregressive/moving-average model was developed to describe the dynamic relationship between mean arterial pressure (MAP), renal sympathetic nerve activity (SNA) and renal blood flow (RBF) in conscious rabbits. The RBF and SNA to the same kidney were measured under resting conditions in a group of eight rabbits. Spectral analysis of the data sampled at 0.4 Hz showed that the low-pass bandwidth of the signal power for RBF was approximately 0. 05 Hz. An autoregressive/moving-average model with an exogenous input (ARMAX) was then derived (using the iterative Gauss-Newton algorithm provided by the MATLAB identification Toolbox), with MAP and SNA as inputs and RBF as output, to model the low-frequency fluctuations. The model step responses of RBF to changes in SNA and arterial pressure indicated an overdamped response with a settling time that was usually less than 2 s. Calculated residuals from the model indicated that 79 5 % (mean s.d., averaged over eight independent experiments) of the variation in RBF could be accounted for by the variations in arterial pressure and SNA. Two additional single-input models for each of the inputs were similarly obtained and showed conclusively that changes in RBF, in the conscious resting rabbit, are a function of both SNA and MAP and that the SNA signal has the predominant effect. These results indicate a strong reliance on SNA for the dynamic regulation of RBF. Such information is likely to be important in understanding the diminished renal function that occurs in a variety of disease conditions in which overactivity of the sympathetic nervous system occurs.

  16. Comparison of two protocols of periosteal distraction osteogenesis in a rabbit calvaria model.

    PubMed

    Saulacic, Nikola; Nakahara, Ken; Iizuka, Tateyuki; Haga-Tsujimura, Maiko; Hofstetter, Willy; Scolozzi, Paolo

    2016-08-01

    The regenerative pathways during periosteal distraction osteogenesis may be influenced by the local environment composed by cells, growth factors, nutrition and mechanical load. The aim of the present study was to evaluate the influence of two protocols of periosteal distraction on bone formation. Custom made distraction devices were surgically fixed onto the calvariae of 60 rabbits. After an initial healing period of 7 days, two groups of animals were submitted to distraction rates of 0.25 and 0.5 mm/24 h for 10 days, respectively. Six animals per group were sacrificed 10 (mid-distraction), 17 (end-distraction), 24 (1-week consolidation), 31 (2-week consolidation) and 77 days (2-month consolidation) after surgery. Newly formed bone was assessed by means of micro-CT and histologically. Expression of transcripts encoding tissue-specific genes (BMP-2, RUNX2, ACP5, SPARC, collagen I α1, collagen II α1 and SOX9) was analyzed by quantitative PCR. Two patterns of bone formation were observed, originating from the old bone surface in Group I and from the periosteum in Group II. Bone volume (BV) and bone mineral density (BMD) significantly increased up to the 2-month consolidation period within the groups (p < 0.05). Significantly more bone was observed in Group II compared to Group I at the 2-month consolidation period (p < 0.001). Expression of transcripts encoding osteogenic genes in bone depended on the time-point of observation (p < 0.05). Low level of transcripts reveals an indirect role of periosteum in the osteogenic process. Two protocols of periosteal distraction in the present model resulted in moderate differences in terms of bone formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1121-1131, 2016.

  17. Hyperphosphorylation of RyRs Underlies Triggered Activity in Transgenic Rabbit Model of LQT2 Syndrome

    PubMed Central

    Terentyev, Dmitry; Rees, Colin M.; Li, Weiyan; Cooper, Leroy L.; Jindal, Hitesh K.; Peng, Xuwen; Lu, Yichun; Terentyeva, Radmila; Odening, Katja E.; Daley, Jean; Bist, Kamana; Choi, Bum-Rak; Karma, Alain; Koren, Gideon

    2015-01-01

    Rationale Loss-of function mutations in HERG potassium channels underlie long QT syndrome (LQTS) type 2 (LQT2), and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasmamembrane-related pathways involved in arrhythmogenesis in LQTS, while pro-arrhythmic changes in intracellular Ca2+ handling remained unexplored. Objective We investigated the remodeling of Ca2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 in order to determine whether these changes contribute to triggered activity in the form of early afterdepolarizations (EADs). Methods and Results Confocal Ca2+ imaging revealed decrease in amplitude of Ca2+ transients and SR Ca2+ content in LQT2 myocytes. Experiments using SR-entrapped Ca2+ indicator demonstrated enhanced RyR-mediated SR Ca2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR in LQT2 myocytes vs. controls. Co-immunoprecipitation experiments demonstrated loss of protein phosphatases type 1 and type 2 from the RyR complex. Stimulation of LQT2 cells with β-adrenergic agonist isoproterenol resulted in prolongation of the plateau of action potentials accompanied by aberrant Ca2+ releases and EADs, which were abolished by inhibition of CaMKII. Computer simulations showed that late aberrant Ca2+ releases caused by RyR hyperactivity promote EADs and underlie the enhanced triggered activity through increased forward mode of NCX1. Conclusions Hyperactive, hyperphosphorylated RyRs due to reduced local phosphatase activity enhance triggered activity in LQT2 syndrome. EADs are promoted by aberrant RyR-mediated Ca2+ releases that are present despite a reduction of sarcoplasmic reticulum (SR) content. Those releases increase forward mode NCX1, thereby slowing repolarization and enabling L-type Ca2+ current reactivation. PMID:25249569

  18. Evaluation of the Effects of Bile on the Arterial Tonus in a Rabbit Model

    PubMed Central

    Mezili, Candan; Tiftikçioğlu, Yiğit Özer; Şirinoğlu, Hakan; Çinar, Mehtap; Kismali, Erkan; Nart, Deniz; Gürler, Tahir; Alper, Mehmet

    2015-01-01

    Background: Hepatic artery anastomosis is an essential part of live-donor liver transplantation, and during this anastomosis, an unusual contact between bile and vessel ends is observed. In this study, the effects of this nonphysiological contact in a rabbit model were evaluated. Methods: The study was designed in 2 steps—in vitro and in vivo. Three groups were established for the in vitro study. In the first group, vessels were incubated in Krebs solution with 5% bile for 1 minute. In the second group, vessels were kept in Krebs solution with 5% bile for 5 minutes. Vessels in the control group were kept in Krebs solution without bile. All groups were examined for responses to vasodilator and vasoconstrictor agents in organ bath system. The specimens were evaluated immunohistochemically and histopathologically. In the in vivo step, microvascular anastomosis was performed bilaterally. Right carotid artery was anastomosed during bile contamination as study group, and left carotid artery was anastomosed without bile contamination as control group. Blood flow indexes were measured. Results: The results of the in vitro study revealed decreased responses to contractile and relaxing agents in the first study group compared with that of the control group (P < 0.0001). There was no response obtained in the second study group. The Doppler ultrasound results revealed no difference between preoperative and postoperative flow indexes (P > 0.05). There was no postoperative spasm in the study group. However, there was significant vasospasm in the control group (P < 0.05). Conclusions: Vessels exposed to bile have decreased contractile and relaxing responses, and this effect increases with exposure duration. PMID:26893995

  19. Intravenous contrast media application using cone-beam computed tomography in a rabbit model

    PubMed Central

    Kim, Min-Sung; Kim, Bok-Yeol; Choi, Hwa-Young; Choi, Yoon-Joo; Oh, Song-Hee; Kang, Ju-Hee; Lee, Sae-Rom; Kang, Ju-Han; Kim, Gyu-Tae; Choi, Yong-Suk

    2015-01-01

    Purpose This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. Materials and Methods CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. Results The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Conclusion Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography. PMID:25793181

  20. Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity

    SciTech Connect

    Brenner, Matthew; Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Lemor, Daniel; Ahdout, Rebecca; Boss, Gerry R.; Blackledge, William; Jann, Lauren; Nagasawa, Herbert T.; Patterson, Steven E.

    2010-11-01

    The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water-soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potential to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment.

  1. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

    PubMed

    Énzsöly, Anna; Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J Mark; Mátyus, Péter; Németh, János

    2013-06-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization.

  2. Biodegradable nanofiber-membrane for sustainable release of lidocaine at the femoral fracture site as a periosteal block: In vitro and in vivo studies in a rabbit model.

    PubMed

    Chou, Ying-Chao; Cheng, Yi-Shiun; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung

    2016-04-01

    The aim of this study was to evaluate the efficacy of a biodegradable, lidocaine-embedded, nanofibrous membrane for the sustainable analgesic release onto fragments of a segmental femoral fracture site. Membranes of three different lidocaine concentrations (10%, 30%, and 50%) were produced via an electrospinning technique. In vitro lidocaine release was assessed by high-performance liquid chromatography. A femoral segmental fracture, with intramedullary Kirschner-wire fixation and polycaprolactone stent enveloping the fracture site, was set-up in a rabbit model for in vivo assessment of post-operative recovery of activity. Eighteen rabbits were randomly assigned to three groups (six rabbits per group): group A comprised of rabbits with femoral fractures and underwent fixation; group B comprised of a comparable fracture model to that of group A with the implantation of lidocaine-loaded nanofibers; and group C, the control group, received only anesthesia. The following variables were measured: change in body weight, food and water intake before and after surgery, and total activity count post-surgery. All membranes eluted effective levels of lidocaine for more than 3 weeks post-surgery. Rabbits in group B showed faster recovery of activity post-operatively, compared with those in group A, which confirmed the pain relief efficacy of the lidocaine-embedded nanofibers. Nanofibers with sustainable lidocaine release have adequate efficacy and durability for pain relief in rabbits with segmental long bone fractures.

  3. Pulsating electromagnetic fields (PEMF) used to treat full thickness defects in the rabbit model

    SciTech Connect

    Andino, R.V.; Feldman, D. )

    1991-03-15

    Skin ulcers have historically been treated by passive therapy. One active treatment, PEMF, has shown promise. The objective of this study was, therefore, to examine the effects of a current induced by a PEMF on full thickness defects in white New Zealand rabbits. It was hypothesized that the induced current would increase neutrophil, macrophage, and fibroblast proliferation during the wound healing process. This in turn, would lead to an increase in collagen deposition in the wound and thus increase the healing rate. A device which produces a 2.8 mTesla magnetic field at a frequency of 75 Hz was donated by the EBI Corp. and modified so that a rabbit could be fit between its two induction coils. Two rabbits with four 3 x 3 cm wounds each were stimulated for 3.5 hours/day for 1 week and two rabbits with identical wounds were stimulated for the same time period daily but for 2 weeks. These wounds were compared to unstimulated controls. Preliminary results indicate that the healing rate in the PEMF animals increased by about 25-30% and the number of neutrophils is greater in the one week stimulated group. In the two week stimulated group, the collagen deposition is greater, denser and in alignment.

  4. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    NASA Technical Reports Server (NTRS)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  5. Development of TWO HD Vapor Exposure Techniques in a Rabbit Ocular Model: A Pilot Study

    DTIC Science & Technology

    2008-05-01

    During evaluations the rabbits were placed in Lomir “Bunny Snuggle” restrainers (Lomir Biomedical, Inc., Malone , NY) for approximately 10-15 minutes...treatments for HD-induced ocular injury. REFERENCES 1. Sidell, F. and Hurst, C.G. Clinical considerations in mustard poisoning . In

  6. Environmental Monitoring for Aspergillus fumigatus in Association with an Immunosuppressed Rabbit Model of Pulmonary Aspergillosis

    PubMed Central

    Such, Kimberly A; Petraitis, Vidmantas; Petraitiene, Ruta; Strauss, Gittel E; Moradi, Patriss-Wais; Walsh, Thomas J

    2013-01-01

    Aspergillus fumigatus causes life-threatening pneumonia in immunocompromised patients. Conidia, the infectious form of the organism, are handled in a biologic safety cabinet under BSL2 conditions. However because germinated conidia form noninfectious hyphae in tissue, we hypothesized that rabbits inoculated intratracheally would grow A. fumigatus in their lungs but that the environment would remain free of this fungus, potentially permitting maintenance of infected animals under ABSL1 conditions. We performed a surveillance study for the presence of A. fumigatus in the environment before proceeding with antifungal therapy studies of experimental pulmonary aspergillosis. The expected outcome included absence of A. fumigatus in the environment, stool, and blood and presence in rabbit lungs. Female SPF New Zealand white rabbits were immunosuppressed and inoculated intratracheally (n = 4) or intraesophageally (n = 2) with 1.25 × 108 conidia of A. fumigatus. Feces, pan liners, and walls were sampled daily during the 11-d experiment, and blood was sampled on days 2, 6, and 8 after inoculation. Samples were cultured on 5% Sabouraud glucose agar plates. Lungs were weighed and scored for hemorrhagic infarcts and homogenized for culture on 5% Sabouraud glucose agar and trypticase soy agar plates. Blood cultures, rabbit stool, and environmental swabs were all negative for A. fumigatus whereas the lungs inoculated intratracheally demonstrated 4.5 × 102 ± 0.8 × 102 CFU/g of A. fumigatus. Therefore, neutropenic rabbits with experimental invasive pulmonary aspergillosis do not shed conidia of A. fumigatus and can be safely housed under ABSL1 conditions after inoculation. PMID:24041208

  7. Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model.

    PubMed

    Goetz, Jessica E; Coleman, Mitchell C; Fredericks, Douglas C; Petersen, Emily; Martin, James A; McKinley, Todd O; Tochigi, Yuki

    2017-03-01

    The goals of this work were to characterize progression of osteoarthritic cartilage degeneration in a rabbit medial meniscus destabilization (MMD) model and then to use the model to identify pre-histologic disruptions in chondrocyte metabolism under chronically elevated joint contact stresses in vivo. To characterize PTOA progression, 24 rabbits received either MMD or sham surgery. Limb loading was analyzed preoperatively and at regular postoperative intervals using a Tekscan pressure-sensitive walkway. Animals were euthanized 8 (n = 8 MMD; n = 8 sham) or 26 weeks (n = 8 MMD) postoperatively for histological cartilage evaluation by an objective, semi-automated Mankin scoring routine. To examine pre-histologic pathology, MMD was performed on an additional 20 rabbits, euthanized 1 (n = 9) or 4 weeks (n = 10) postoperatively. Chondrocytes were harvested fresh for measurement of mitochondrial function, an intracellular indicator of pathology after mechanical injury. Both MMD and sham surgery caused slight decreases in limb loading which returned to preoperative levels after 2 weeks. Histologically apparent cartilage damage progressed from 8 to 26 weeks after MMD. Changes in chondrocyte respiration were variable at 1 week, but by 4 weeks postoperatively chondrocyte mitochondrial function was significantly reduced. Many human injuries that lead to PTOA are relatively mild, and the cell-level mechanisms leading to disease remain unclear. We have documented PTOA progression in an animal model of subtle joint injury under continued use, and demonstrated that this model provides a realistic environment for investigation of multi-stage cellular pathology that develops prior to overt tissue degeneration and which could be targeted for disease modifying treatments. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:590-599, 2017.

  8. Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

    PubMed Central

    Seidensticker, Max; Streit, Sebastian; Nass, Norbert; Wybranski, Christian; Jürgens, Julian; Brauner, Jan; Schulz, Nadine; Kalinski, Thomas; Seidensticker, Ricarda; Garlipp, Benjamin; Steffen, Ingo; Ricke, Jens; Dudeck, Oliver

    2016-01-01

    PURPOSE We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model. METHODS VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy. RESULTS The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE. CONCLUSION SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity. PMID:27328720

  9. Research on the Stability of a Rabbit Dry Eye Model Induced by Topical Application of the Preservative Benzalkonium Chloride

    PubMed Central

    Luan, Shaohong; Wan, Pengxia; Li, Naiyang; Tang, Jing; Han, Yu; Xiong, Cuiju; Wang, Zhichong

    2012-01-01

    Background Dry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model. Methods and Findings Eighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 (P<0.05) and in Group BAC-W5 on day 14 (P<0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points (P<0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21. Conclusions A stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye). PMID:22438984

  10. Development of a Novel Rabbit Model of Abdominal Aortic Aneurysm via a Combination of Periaortic Calcium Chloride and Elastase Incubation

    PubMed Central

    Xu, Ke; Zhang, Zhen; Qi, Xun; Xia, Yonghui; Ren, Ling

    2013-01-01

    Background The purpose of this study was to introduce a novel, simple and effective technique for creating a reliable rabbit model of abdominal aortic aneurysm (AAA) via a combination of periaortic calcium chloride (CaCl2) and elastase incubation. Methods Forty-eight New Zealand white rabbits were divided into four groups. The AAA model was developed via a 20-minute periaortic incubation of CaCl2 (0.5 mol/L) and elastase (1 Unit/µL) in a 1.5-cm aortic segment (Group CE). A single incubation of CaCl2 (Group C) or elastase (Group E) and a sham operation group (Sham Group) were used for the controls. Diameter was measured by serial digital subtraction angiography imaging on days 5, 15 and 30. Animals were sacrificed on day 5 and day 30 for histopathological and immunohistochemical studies. Results All animals in Group CE developed aneurysm, with an average dilation ratio of 65.3%±8.9% on day 5, 86.5%±28.7% on day 15 and 203.6%±39.1% on day 30. No aneurysm was found in Group C, and only one aneurysm was seen on day 5 in Group E. Group CE exhibited less intima-media thickness, endothelial recovery, elastin and smooth muscle cell (SMC) content, but stronger expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and RAM11 compared to the controls. Conclusions The novel rabbit model of AAA created by using a combination of periaortic CaCl2 and elastase incubation is simple and effective to perform and is valuable for elucidating AAA mechanisms and therapeutic interventions in experimental studies. PMID:23844207

  11. Endovascular biopsy: Technical feasibility of novel endothelial cell harvesting devices assessed in a rabbit aneurysm model

    PubMed Central

    Bauer, Diana; Sun, Zhengda; Stillson, Carol; Nelson, Jeffrey; Barry, David; Hetts, Steven W; Higashida, Randall T; Dowd, Christopher F; Halbach, Van V; Su, Hua; Saeed, Maythem M

    2015-01-01

    The lack of safe and reliable methods to sample vascular tissue in situ limits discovery of the underlying genetic and pathophysiological mechanisms of many vascular disorders, including aneurysms. We investigated the feasibility and comparable efficacy of in vivo vascular endothelial cell sampling using a spectrum of endovascular devices. Using the rabbit elastase carotid aneurysm model we evaluated the performance of existing aneurysmal coils, intracranial stents, and stent-like devices to collect vascular endothelial cells. Additionally, we modified a subset of devices to assess the effects of alterations to coil pitch, coil wire contour, and stent surface finishing. Device performance was evaluated by (1) the number of viable endothelial cells harvested, (2) the degree of vascular wall damage analyzed using digital subtraction angiography and histopathological analysis, and (3) the ease of device navigability and retrieval. Isolated cells underwent immunohistochemical analysis to confirm cell type and viability. Coil and stent specifications, technique, and endothelial cell counts were tabulated and statistical analysis performed. Using conventional detachable-type and modified aneurysm coils 11 of 14 (78.6%) harvested endothelial cells with a mean of 7.93 (±8.33) cells/coil, while 15 of 15 (100%) conventional stents, stent-like devices and modified stents harvested endothelial cells with a mean of 831.33 (±887.73) cells/device. Coil stiffness was significantly associated with endothelial cell count in univariate analysis (p = 0.044). For stents and stent-like devices univariate analysis demonstrated stent-to-aorta diameter ratios (p = 0.001), stent length (p = 0.049), and the use of a pulling retrieval technique (p = 0.019) significantly predictive of endothelial cell counts, though a multivariate model using these variables demonstrated only the stent-to-aorta diameter ratio (p = 0.029) predictive of endothelial cell counts. Modified

  12. Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

    NASA Astrophysics Data System (ADS)

    Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

    2012-10-01

    Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

  13. Efficacy of ceftaroline fosamil against penicillin-sensitive and -resistant streptococcus pneumoniae in an experimental rabbit meningitis model.

    PubMed

    Cottagnoud, P; Cottagnoud, M; Acosta, F; Stucki, A

    2013-10-01

    Ceftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain of S. pneumoniae in an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

  14. [The effect of betahistine on histological changes in rabbit brain in model of whole body wide-frequency vibration].

    PubMed

    Shimkus, Iu Iu; Sapegin, I D

    2013-01-01

    In acute experiments in conscious rabbits was studied protective action of selective blocker of histamine H3-receptor betahistine (2mg/kg i/v) against histological changes in precentral and postcentral gyrus, as well as in temporal lobe of cerebral cortex, thalamus, hypothalamus, and cerebellum, arising in case of modeling of whole body wide-frequency vibration. Betahistine attenuates edematous and degenerative changes in neurons and reciprocal glial reaction, caused by vibration, but does not eliminate edema in perivascular spaces. This effect may be related to the improvement of blood supply as a result of of vasodilatory action and decrease of oxygen consumption via vestibuloprotective effect.

  15. Rabbit models of arthritis: immunolocalization of matrix metalloproteinases and tissue inhibitor of metalloproteinase in synovium and cartilage.

    PubMed Central

    Hembry, R. M.; Bagga, M. R.; Murphy, G.; Henderson, B.; Reynolds, J. J.

    1993-01-01

    The distribution of the matrix metalloproteinases, collagenase, stromelysin, gelatinases A and B, and the tissue inhibitor of metalloproteinases in cartilage and synovium removed from rabbits up to 27 days after induction of two models of arthritis was investigated by immunolocalization. Following intra-articular injection of poly-D-lysine/hyaluronic acid coacervate, collagenase and stromelysin were found bound to cartilage matrix, but there was little increase in chondrocyte synthesis of these enzymes. The synovium underwent a complex wound healing response involving invagination and encapsulation of the coacervate and inflammatory cell debris, during which all four metalloproteinases and tissue inhibitor of metalloproteinase could be immunolocalized. The second model, intra-articular injection of ovalbumin into sensitized rabbits, caused considerable chondrocyte necrosis; collagenase was found bound to cartilage matrix on day 13, although again there was little evidence of synthesis by chondrocytes. Inflammatory cell infiltration of meniscoid synovia took place initially, followed by fibrosis involving macrophagelike cells secreting gelatinase A. In both models there was rapid loss of glycosaminoglycan metachromasia from the cartilage matrix. These results are discussed in relation to current knowledge of metalloproteinase involvement in the chronic rheumatoid synovial pannus erosion of cartilage in humans. The data suggest that there are considerable differences between rheumatoid arthritis and these models, and their use must therefore be carefully defined. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8342606

  16. Combined Low-Frequency Ultrasound and Urokinase-Containing Microbubbles in Treatment of Femoral Artery Thrombosis in a Rabbit Model

    PubMed Central

    Mu, Yuming

    2016-01-01

    This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects. PMID:28033371

  17. Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model.

    PubMed

    Kaderli, Sema; Viguier, Eric; Watrelot-Virieux, Dorothée; Roger, Thierry; Gurny, Robert; Scapozza, Leonardo; Möller, Michael; Boulocher, Caroline; Jordan, Olivier

    2015-10-01

    Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by μCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective

  18. Vaccination sequence effects on immunological response and tissue bacterial burden in paratuberculosis infection in a rabbit model.

    PubMed

    Arrazuria, Rakel; Molina, Elena; Garrido, Joseba M; Pérez, Valentín; Juste, Ramón A; Elguezabal, Natalia

    2016-08-05

    Paratuberculosis (PTB), a chronic granulomatous enteritis produced by Mycobacterium avium subspecies paratuberculosis (MAP), is considered as one of the diseases with the highest economic impact in the ruminant industry. Vaccination against MAP is recommended during the first months after birth on the basis that protection would be conferred before the first contact with mycobacteria. However, little is known about the therapeutic effect of MAP vaccination in controlled experimental conditions. The current study was designed to evaluate the efficacy of vaccination before and after challenge with MAP in a rabbit infection model. The rabbits were divided into four groups: non-infected control (NIC, n = 4), infected control challenged with MAP (IC, n = 5), vaccinated and challenged 1 month after with MAP (VSI, n = 5) and challenged with MAP and vaccinated 2 months later (IVS, n = 5). The results from this study show a quick increase in IFN-γ release upon stimulation with bovine, avian and johnin PPD in animals vaccinated before MAP challenge. All vaccinated animals show an increased humoral response as seen by western blot and ELISA. The final bacteriology index (considering tissue culture and qPCR) shows that the IC group was the most affected. Vaccination after infection (IVS) produced the lowest bacteriology index showing significant differences with the IC group (p = 0.034). In conclusion, vaccination against MAP shows positive effects in a rabbit model. However, vaccination after infection shows a slightly stronger protective effect compared to vaccination before infection, suggesting a therapeutic effect. This feature could be applied to previously infected adult animals under field conditions.

  19. Impact of Stent Design on In-Stent Stenosis in a Rabbit Iliac Artery Model

    SciTech Connect

    Sommer, C. M. Grenacher, L.; Stampfl, U.; Arnegger, F. U.; Rehnitz, C.; Thierjung, H.; Stampfl, S.; Berger, I.; Richter, G. M.; Kauczor, H. U.; Radeleff, B. A.

    2010-06-15

    The purpose of this study was to evaluate the impact of stent design on in-stent stenosis in rabbit iliac arteries. Four different types of stent were implanted in rabbit iliac arteries, being different in stent design (crown or wave) and strut thickness (50 or 100 {mu}m). Ten stents of each type were implanted. Each animal received one crown and one wave stent with the same strut thickness. Follow-up was either 12 weeks (n = 10 rabbits) or 24 weeks (n = 10 rabbits). Primary study end points were angiographic and microscopic in-stent stenosis. Secondary study end points were vessel injury, vascular inflammation, and stent endothelialization. Average stent diameter, relative stent overdilation, average and minimal luminal diameter, and relative average and maximum luminal loss were not significantly different. However, a trend to higher relative stent overdilation was recognized in crown stents compared to wave stents. A trend toward higher average and minimal luminal diameter and lower relative average and maximum luminal loss was recognized in crown stents compared to wave stents with a strut thickness of 100 {mu}m. Neointimal height, relative luminal area stenosis, injury score, inflammation score, and endothelialization score were not significantly different. However, a trend toward higher neointimal height was recognized in crown stents compared to wave stents with a strut thickness of 50 {mu}m and a follow-up of 24 weeks. In conclusion, in this study, crown stents seem to trigger neointima. However, the optimized radial force might equalize the theoretically higher tendency for restenosis in crown stents. In this context, also more favorable positive remodeling in crown stents could be important.

  20. Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

    PubMed Central

    Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

    2012-01-01

    Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

  1. Evaluation of a biodegradable graft substitute in rabbit bone defect model

    PubMed Central

    Yang, XiaoBo; Li, Yong; Huang, Qiang; Yang, Jing; Shen, Bing; Pei, FuXing

    2012-01-01

    Objective: To evaluate a new biodegradable copolymer calcium sulfate/poly amino acid (CS/PAA) as a graft substitute for the repair of the surgically created cancellous bone defects in rabbits and its biological properties in vivo. Materials and Methods: Cancellous bone defects were created by drilling holes in the unilateral lateral aspect of the femoral condyle of New Zealand white rabbits. Three groups were assigned: Group A rabbits were grafted with 80% CS/PAA and group B rabbits were grafted with 95% CS/PAA as two treatment groups; group C was sham-operation control group. To study the osteogenic capability in vivo, specimens were harvested at 4, 8, 12, and 16 weeks after implantation and were evaluated by gross assessment, X-ray, histological examination, and histomorphometry. In order to identify the molecular mechanism of bone defect repair, the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) was detected using Western blot at 4 weeks. Results: Group A and group B showed more vigorous and rapid repair leading to regeneration of cancellous bone than sham-operation control group on gross observation, radiology, and histomorphometry. There was no significant difference between groups A and B. Morphological observation and histological examination showed that the copolymers degraded in sync with the new bone formation process. The expression of BMP-2 and VEGF in implantation groups was higher than that in control group by western blot. Conclusion: These findings demonstrated that the novel biodegradable copolymers can repair large areas of cancellous bone defects. With its controllable degradation rate, it suggests that CS/PAA may be a series of useful therapeutic substitute for bone defects. PMID:22719111

  2. Specific contrast ultrasound using sterically stabilized microbubbles for early diagnosis of thromboembolic disease in a rabbit model.

    PubMed

    Vlašín, Michal; Lukáč, Robert; Kauerová, Zuzana; Kohout, Pavel; Mašek, Josef; Bartheldyová, Eliška; Koudelka, Štěpán; Korvasová, Zina; Plocková, Jana; Hronová, Nikola; Turánek, Jaroslav

    2014-04-01

    Specific contrast ultrasound is widely applied in diagnostic procedures on humans but remains underused in veterinary medicine. The objective of this study was to evaluate the use of microbubble-based contrast for rapid ultrasonographic diagnosis of thrombosis in small animals, using male New Zealand white rabbits (average weight about 3.5 kg) as a model. It was hypothesized that the use of microbubble-based contrast agents will result in a faster and more precise diagnosis in our model of thrombosis. A pro-coagulant environment had been previously established by combining endothelial denudation and external vessel wall damage. Visualization of thrombi was achieved by application of contrast microbubbles [sterically stabilized, phospholipid-based microbubbles filled with sulfur hexafluoride (SF₆) gas] and ultrasonography. As a result, rapid and clear diagnosis of thrombi in aorta abdominalis was achieved within 10 to 30 s (mean: 17.3 s) by applying microbubbles as an ultrasound contrast medium. In the control group, diagnosis was not possible or took 90 to 180 s. Therefore, sterically stabilized microbubbles were found to be a suitable contrast agent for the rapid diagnosis of thrombi in an experimental model in rabbits. This contrast agent could be of practical importance in small animal practice for rapid diagnosis of thrombosis.

  3. Three-dimensional surface geometries of the rabbit soleus muscle during contraction: input for biomechanical modelling and its validation.

    PubMed

    Böl, Markus; Leichsenring, Kay; Weichert, Christine; Sturmat, Maike; Schenk, Philipp; Blickhan, Reinhard; Siebert, Tobias

    2013-11-01

    There exists several numerical approaches to describe the active contractile behaviour of skeletal muscles. These models range from simple one-dimensional to more advanced three-dimensional ones; especially, three-dimensional models take up the cause of describing complex contraction modes in a realistic way. However, the validation of such concepts is challenging, as the combination of geometry, material and force characteristics is so far not available from the same muscle. To this end, we present in this study a comprehensive data set of the rabbit soleus muscle consisting of the muscles' characteristic force responses (active and passive), its three-dimensional shape during isometric, isotonic and isokinetic contraction experiments including the spatial arrangement of muscle tissue and aponeurosis-tendon complex, and the fascicle orientation throughout the whole muscle at its optimal length. In this way, an extensive data set is available giving insight into the three-dimensional geometry of the rabbit soleus muscle and, further, allowing to validate three-dimensional numerical models.

  4. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model.

    PubMed

    Aly, Eman; Ebrahim, Amal

    2016-04-01

    The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 μg, 1.76 μmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ˂ 0.05) in a- and b-wave, a time-dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function.

  5. FDTD analysis of temperature elevation in the lens of human and rabbit models due to near-field and far-field exposures at 2.45 GHz.

    PubMed

    Oizumi, Takuya; Laakso, Ilkka; Hirata, Akimasa; Fujiwara, Osamu; Watanabe, Soichi; Taki, Masao; Kojima, Masami; Sasaki, Hiroshi; Sasaki, Kazuyuki

    2013-07-01

    The eye is said to be one of the most sensitive organs to microwave heating. According to previous studies, the possibility of microwave-induced cataract formation has been experimentally investigated in rabbit and monkey eyes, but not for the human eye due to ethical reasons. In the present study, the temperature elevation in the lens, the skin around the eye and the core temperature of numerical human and rabbit models for far-field and near-field exposures at 2.45 GHz are investigated. The temperature elevations in the human and rabbit models were compared with the threshold temperatures for inducing cataracts, thermal pain in the skin and reversible health effects such as heat exhaustion or heat stroke. For plane-wave exposure, the core temperature elevation is shown to be essential both in the human and in the rabbit models as suggested in the international guidelines and standards. For localised exposure of the human eye, the temperature elevation of the skin was essential, and the lens temperature did not reach its threshold for thermal pain. On the other hand, the lens temperature elevation was found to be dominant for the rabbit eye.

  6. Augmentation of Chemotherapeutic Infusion Effect by TSU-68, an Oral Targeted Antiangiogenic Agent, in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Kim, Hyo-Cheol; Chung, Jin Wook Choi, Seung Hong; Im, Seock-Ah; Yamasaki, Yasundo; Jun, Suryoung; Jae, Hwan Jun; Park, Jae Hyung

    2012-02-15

    Purpose: This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model. Methods: This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performed before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections. Results: According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02). Conclusions: Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.

  7. Development and validation of a computational finite element model of the rabbit upper airway: simulations of mandibular advancement and tracheal displacement.

    PubMed

    Amatoury, Jason; Cheng, Shaokoon; Kairaitis, Kristina; Wheatley, John R; Amis, Terence C; Bilston, Lynne E

    2016-04-01

    The mechanisms leading to upper airway (UA) collapse during sleep are complex and poorly understood. We previously developed an anesthetized rabbit model for studying UA physiology. On the basis of this body of physiological data, we aimed to develop and validate a two-dimensional (2D) computational finite element model (FEM) of the passive rabbit UA and peripharyngeal tissues. Model geometry was reconstructed from a midsagittal computed tomographic image of a representative New Zealand White rabbit, which included major soft (tongue, soft palate, constrictor muscles), cartilaginous (epiglottis, thyroid cartilage), and bony pharyngeal tissues (mandible, hard palate, hyoid bone). Other UA muscles were modeled as linear elastic connections. Initial boundary and contact definitions were defined from anatomy and material properties derived from the literature. Model parameters were optimized to physiological data sets associated with mandibular advancement (MA) and caudal tracheal displacement (TD), including hyoid displacement, which featured with both applied loads. The model was then validated against independent data sets involving combined MA and TD. Model outputs included UA lumen geometry, peripharyngeal tissue displacement, and stress and strain distributions. Simulated MA and TD resulted in UA enlargement and nonuniform increases in tissue displacement, and stress and strain. Model predictions closely agreed with experimental data for individually applied MA, TD, and their combination. We have developed and validated an FEM of the rabbit UA that predicts UA geometry and peripharyngeal tissue mechanical changes associated with interventions known to improve UA patency. The model has the potential to advance our understanding of UA physiology and peripharyngeal tissue mechanics.

  8. The effect of a biphasic injectable bone substitute on the interface strength in a rabbit knee prosthesis model

    PubMed Central

    2013-01-01

    Background In joint prosthetic surgery, various methods are used to provide implant stability. We used an injectable bone substitute, composed of calcium sulfate/hydroxyapatite, as bone defect filler to stabilize a tibia prosthesis in an experimental rabbit model. The aim of the study was to investigate and compare the stability of prosthetic fixation with and without the use of an injectable bone substitute. Methods Sixteen rabbits were used and the tibia prostheses were implanted bilaterally, one side with the prosthesis alone and the other side with the prosthesis and calcium sulfate/hydroxyapatite (Cerament™). The rabbits were randomly divided into two groups and euthanized after 6 and 12 weeks, respectively. The prosthesis was extracted measuring the pull-out force in an Instron tester, and the bone surrounding the former prosthesis site was analyzed by histology, histomorphometry, and micro-computed tomography. Results At 6 weeks no difference in maximum pull-out force was found between the prostheses fixed with or without Cerament™. At 12 weeks the maximum pull-out force for the prostheses with Cerament™ was significantly higher than that for the prostheses without Cerament™ (p = 0.04). The maximum pull-out force at 12 weeks was significantly higher than that at 6 weeks for the prostheses fixed with Cerament™ (p = 0.03) but not for the prostheses without. Conclusion We conclude that early prosthesis-bone interface strength is not influenced by a bone substitute. However, during remodeling, the bone substitute might provide improved mechanical support for the prosthesis. The results support further studies of the use of injectable calcium sulfate/hydroxyapatite in fixation of prosthetic joint implants. PMID:23899023

  9. Effects of a Temperature-Sensitive, Anti-Adhesive Agent on the Reduction of Adhesion in a Rabbit Laminectomy Model

    PubMed Central

    Park, Jeong Woo; Cho, Tae Koo; Chun, Hyoung-Joon; Ryu, Je Il

    2016-01-01

    Objective A common cause of failure in laminectomy surgery is when epidural, peridural, or perineural adhesion occurs postoperatively. The purpose of this study is to examine the efficacy of a temperature-sensitive, anti-adhesive agent (TSAA agent), Guardix-SG®, as a mechanical barrier for the prevention or reduction of peridural scar adhesion in a rabbit laminectomy model. Methods Twenty-six mature rabbits were used for this study. Each rabbit underwent two separate laminectomies at lumbar vertebrae L3 and L6, left empty (the control group) and applied 2 mL of the TSAA agent (the experimental group), respectively. Invasive scar formation or inflammation after laminectomy was quantitatively evaluated by measuring the thickness of the dura, the distance from the surface of dura to the scar tissues, the number of inflammatory cells in the scar tissues at the laminectomy site, and the concentration of collagen in histological sections. Results At 6 weeks postsurgery, the dura was significantly thinner and the distance from the surface of dura to the scar tissues was greater in the experimental group than in the control group (p=0.04 and p=0.01). The number of inflammatory cells was not significantly different in the two groups (p=0.08), although the mean number of inflammatory cells was relatively lower in the experimental group than in the control group. Conclusion The current study suggests that the TSAA agent, Guardix-SG®, could be useful as an interpositional physical barrier after laminectomy for the prevention or reduction of adhesion. PMID:27226857

  10. Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model.

    PubMed

    Wu, Edward C; Sun, Victor; Manuel, Cyrus T; Protsenko, Dmitriy E; Jia, Wangcun; Nelson, J Stuart; Wong, Brian J F

    2013-11-01

    Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO2) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO2 spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12-14 J/cm(2) per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO2 spray (pulse duration 33-85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50-70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO2 spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress.

  11. Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome.

    PubMed

    Ziv, Ohad; Morales, Eduardo; Song, Yoon-kyu; Peng, Xuwen; Odening, Katja E; Buxton, Alfred E; Karma, Alain; Koren, Gideon; Choi, Bum-Rak

    2009-10-01

    Enhanced dispersion of repolarization has been proposed as an important mechanism in long QT related arrhythmias. Dispersion can be dynamic and can be augmented with the occurrence of spatially out-of-phase action potential duration (APD) alternans (discordant alternans; DA). We investigated the role of tissue heterogeneity in generating DA using a novel transgenic rabbit model of type 2 long QT syndrome (LQT2). Littermate control (LMC) and LQT2 rabbit hearts (n = 5 for each) were retrogradely perfused and action potentials were mapped from the epicardial surface using di-4-ANEPPS and a high speed CMOS camera. Spatial dispersion (Delta APD and Delta slope of APD restitution) were both increased in LQT2 compared to LMC (Delta APD: 34 +/- 7 ms vs. 23 +/- 6 ms; Delta slope: 1.14 +/- 0.23 vs. 0.59 +/- 0.19). Onset of DA under a ramp stimulation protocol was seen at longer pacing cycle length (CL) in LQT2 compared to LMC hearts (206 +/- 24 ms vs. 156 +/- 5 ms). Nodal lines between regions with APD alternans out of phase from each other were correlated with conduction velocity (CV) alternation in LMC but not in LQT2 hearts. In LQT2 hearts, larger APD dispersion was associated with onset of DA at longer pacing CL. At shorter CLs, closer to ventricular fibrillation induction (VF), nodal lines in LQT2 (n = 2 out of 5) showed persistent complex beat-to-beat changes in nodal line formation of DA associated with competing contribution from CV restitution and tissue spatial heterogeneity, increasing vulnerability to conduction block. In conclusion, tissue heterogeneity plays a significant role in providing substrate for ventricular arrhythmia in LQT2 rabbits by facilitating DA onset and contributing to unstable nodal lines prone to reentry formation.

  12. Thrombin effectuates therapeutic arteriogenesis in the rabbit hindlimb ischemia model: A quantitative analysis by computerized in vivo imaging

    NASA Astrophysics Data System (ADS)

    Kagadis, George C.; Karnabatidis, Dimitrios; Katsanos, Konstantinos; Diamantopoulos, Athanassios; Samaras, Nikolaos; Maroulis, John; Siablis, Dimitrios; Nikiforidis, George C.

    2006-12-01

    We report on an experimental mammalian controlled study that documents arteriogenic capacity of thrombin and utilizes computerized algorithms to quantify the newly formed vessels. Hindlimb ischemia was surgically invoked in 10 New Zealand white rabbits. After quiescence of endogenous angiogenesis heterologous bovine thrombin was intramuscularly injected (1500 units) in one hindlimb per rabbit (Group T). Contralateral limbs were infused with normal saline (Group C). Digital subtraction angiography (DSA) of both limbs was performed after thrombin infusion by selective cannulation of the abdominal aorta and digital images were post-processed with computerized algorithms in order to enhance newly formed vessels. Total vessel area and total vessel length were quantified. In vivo functional evaluation included measurements of blood flow volume at the level of the external iliac artery by Doppler ultrasonography both at baseline and at 20 days after thrombin infusion. Total vessel area and length (in pixels) were 14,713±1023 and 5466±1327 in group T versus 12,015±2557 and 4598±1269 in group C ( p=0.0062 and 0.1526, respectively). Blood flow volumes (ml/min) at baseline and at 20 days after thrombin infusion were 25.87±11.09 and 38.06±11.72 in group T versus 26.57±11.19 and 20.35±7.20 in group C ( p=0.8898 and 0.0007, respectively). Intramuscular thrombin effectuates an arteriogenic response in the rabbit hindlimb ischemia model. Computerized algorithms may enable accurate quantification of the neovascularization outcome.

  13. Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model

    PubMed Central

    Vázquez, Natalia; Chacón, Manuel; Rodríguez-Barrientos, Carlos A.; Merayo-Lloves, Jesús; Naveiras, Miguel; Baamonde, Begoña; Alfonso, Jose F.; Zambrano-Andazol, Iriana; Riestra, Ana C.; Meana, Álvaro

    2016-01-01

    Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world’s population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction

  14. Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model.

    PubMed

    Zhang, Xin; Jia, Weitao; Gu, Yifei; Xiao, Wei; Liu, Xin; Wang, Deping; Zhang, Changqing; Huang, Wenhai; Rahaman, Mohamed N; Day, Delbert E; Zhou, Nai

    2010-08-01

    The treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. In this work, pellets composed of a chitosan-bonded mixture of borate bioactive glass particles (<50microm) and teicoplanin powder (antibiotic), were evaluated in vitro and in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. When immersed in phosphate-buffered saline, the pellets showed sustained release of teicoplanin over 20-30 days, while the bioactive glass converted to hydroxyapatite (HA) within 7 days, eventually forming a porous HA structure. Implantation of the teicoplanin-loaded pellets in a rabbit tibia osteomyelitis model resulted in the detection of teicoplanin in the blood for about 9 days. The implants converted to a bone-like HA graft, and supported the ingrowth of new bone into the tibia defects within 12 weeks of implantation. Microbiological, histological and scanning electron microscopy techniques showed that the implants provided a cure for the bone infection. The results indicate that the teicoplanin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone ingrowth, could provide a method for treating chronic osteomyelitis.

  15. Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model

    PubMed Central

    HUANG, SHENG-LI; JIAO, JIAN; YAN, HONG-WEI

    2016-01-01

    A growing body of evidence suggests that hydrogen is a novel, selective antioxidant that exerts a protective effect against organ damage. The present study investigated the effect of hydrogen-rich saline on corticosteroid-induced necrosis of the femoral head in an animal model established using prednisolone. A total of 30 healthy, male, adult New Zealand white rabbits were randomly divided into two groups: Hydrogen-rich saline (treated with hydrogen-rich saline via intraperitoneal injection) and placebo (treated with normal saline). At the set time-points, the structure of the femoral head was examined using a microscope; the concentrations of glutathione (GSH), lipid peroxide (LPO), vascular endothelial growth factor (VEGF) and thrombomodulin (TM) in the plasma were measured and the microvessel density was quantified. The results showed that hydrogen-rich saline significantly decreased the levels of VEGF, TM and LPO and increased the GSH level in steroid-associated necrosis of the femoral head in the rabbit model. A significant increase in the microvessel density was observed in the hydrogen-rich saline group. Histopathological staining confirmed the results of the biochemical analysis. The present study demonstrates that hydrogen treatment may alleviate steroid-associated osteonecrosis by inhibiting oxidative stress. Hydrogen-rich saline may provide an alternative treatment for steroid-associated necrosis of the femoral head. PMID:26889236

  16. Rabbit model for osteoarthrosis of the temporomandibular joint as a basis for assessment of outcomes after intervention.

    PubMed

    Artuzi, Felipe Ernesto; Langie, Renan; Abreu, Maíra Cavallet de; Quevedo, Alexandre Silva; Corsetti, Adriana; Ponzoni, Deise; Puricelli, Edela

    2016-06-01

    Osteoarthritis can be induced in the temporomandibular joint (TMJ) by primary or secondary trauma, or overloading of the joint. We have therefore systematically evaluated the histological progression of experimental osteoarthritis induced by a high concentration of monosodium iodoacetate into the rabbit TMJ. These findings may contribute to the establishment of a protocol to investigate the benefits of treatment of osteoarthritis of the TMJ. We used 21 male New Zealand rabbits; the 15 in the test group were given an intra-articular injection of monosodium iodoacetate 10mg/ml into the right TMJ and were killed after 60 (n=5), 80 (n=5), and 100 days (n=5). The six in the control group were given an injection of saline into the right TMJ. The assessment system for osteoarthritis based on six grades was used for the histological analysis of severity. The model was effective in producing histological changes in the cartilage consistent with those found in osteoarthritis at all time points. The within-group analysis indicated that the disease did not progress after 60 days. The successful induction of osteoarthritis in this way, its stabilisation after 60 days, and the appropriate size of the animal suggest that this experimental model is ideal for future studies of the effectiveness of treatment in osteoarthritis of the TMJ.

  17. Thermoablation of Malignant Kidney Tumors Using Magnetic Nanoparticles: An In Vivo Feasibility Study in a Rabbit Model

    SciTech Connect

    Bruners, Philipp; Braunschweig, Till; Hodenius, Michael; Pietsch, Hubertus; Penzkofer, Tobias; Baumann, Martin; Guenther, Rolf W.; Schmitz-Rode, Thomas; Mahnken, Andreas H.

    2010-02-15

    The objective of this study was to assess the technical feasibility of CT-guided magnetic thermoablation for the treatment of malignant kidney tumors in a VX2 tumor rabbit model. VX2 tumors were implanted into the kidneys of five rabbits and allowed to grow for 2 weeks. After preinterventional CT perfusion imaging, CT-guided injection of superparamagnetic iron oxide particles (300 {mu}l) was performed, followed by exposure of the animals to an alternating electromagnetic field for 15 min ({approx}0.32 kA/m). Then animals underwent CT perfusion imaging again. Afterward, animals were sacrificed and kidneys were dissected for macroscopic and histological evaluation. Changes in perfusion before and after exposure to the alternating magnetic field were analyzed. In one animal no tumor growth could be detected so the animal was used for optimization of the ablation procedure including injection technique and peri-interventional cross-sectional imaging (CT, MRI). After image-guided intratumoral injection of ferrofluids, the depiction of nanoparticle distribution by CT correlated well with macroscopic evaluation of the dissected kidneys. MRI was limited due to severe susceptibility artefacts. Postinterventional CT perfusion imaging revealed a perfusion deficiency around the ferrofluid deposits. Histological workup showed different zones of thermal damage adjacent to the ferrofluid deposits. In conclusion, CT-guided magnetic thermoablation of malignant kidney tumors is technically feasible in an animal model and results in a perfusion deficiency indicating tumor necrosis as depicted by CT perfusion imaging and shown in histological evaluation.

  18. Formulation of cidofovir improves the anti-papillomaviral activity of topical treatments in the CRPV/rabbit model

    PubMed Central

    Christensen, Neil D.; Cladel, Nancy M.; Hu, Jiafen; Balogh, Karla K.

    2014-01-01

    Current topical treatments for papillomas use ablative, cytotoxic and immunomodulating strategies and reagents. However, the effectiveness of topical treatments using different formulations has not been examined in preclinical models or clinical trials. The purpose of this study was to determine whether formulation of the small molecule acyclic nucleoside, cidofovir (CDV), could lead to improved therapeutic endpoints following topical treatment of papillomas using the cottontail rabbit papillomavirus (CRPV)/rabbit model. Different formulations with a set dose of 1% cidofovir were tested to establish comparative data. The results demonstrated that anti-papilloma treatments with topical CDV were greatly enhanced when formulated versus unformulated. Best results were obtained with CDV formulated in cremophor, then in carbomer 940, and then in DMSO. Further studies indicated that effective formulations led to complete cures of papillomas at dilutions less than 0.3% CDV. These studies together with previous observations demonstrated that unformulated CDV under the same treatment regime required doses of 2% to achieve cures demonstrating that much less compound can be used when properly formulated. PMID:24946003

  19. Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion.

    PubMed

    Engels, Alexander C; Brady, Paul D; Kammoun, Molka; Finalet Ferreiro, Julio; DeKoninck, Philip; Endo, Masayuki; Toelen, Jaan; Vermeesch, Joris R; Deprest, Jan

    2016-02-01

    Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

  20. Pulmonary transcriptome analysis in the surgically induced rabbit model of diaphragmatic hernia treated with fetal tracheal occlusion

    PubMed Central

    Engels, Alexander C.; Brady, Paul D.; Kammoun, Molka; Finalet Ferreiro, Julio; DeKoninck, Philip; Endo, Masayuki; Toelen, Jaan; Vermeesch, Joris R.; Deprest, Jan

    2016-01-01

    ABSTRACT Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH. PMID:26744354

  1. Use of human amniotic membrane wrap in reducing perineural adhesions in a rabbit model of ulnar nerve neurorrhaphy.

    PubMed

    Kim, S S; Sohn, S K; Lee, K Y; Lee, M J; Roh, M S; Kim, C H

    2010-03-01

    The object of this experimental study was to assess the effect of wrapping human amniotic membrane around a repaired ulnar nerve in a rabbit model of perineural adhesion. Ulnar nerves from 10 white New Zealand rabbits were exposed bilaterally, dissected and repaired. Human amniotic membrane was then wrapped around the repair site in one limb with no such wrap in the neurorrhaphy of the contralateral limb. Three months later, the same nerves were re-explored and removed using microsurgical external neurolysis. Perineural adhesion around the ulnar nerve was evaluated by blinded surgical dissection and scored using a visual 4-point qualitative scale. Extent and grade of fibrosis around repair sites were measured microscopically (x 200) after Masson trichrome staining using measure of the depth of fibrosis and the grading criteria of adhesion. Quantitative morphometric analysis was also performed under light microscopy (x 200) with the aid of a digital counter and virtual slide imaging software (ScanScope T2, Vista, CA, USA). Human amniotic membrane wrapped nerves showed significantly less perineural adhesion and fibrosis than controls (P < 0.05). No nerve healing problems were encountered. This study suggests that human amniotic membrane application can reduce fibrosis and adhesion around neurorrhaphy sites in this animal model.

  2. Urethral reconstruction with a 3D porous bacterial cellulose scaffold seeded with lingual keratinocytes in a rabbit model.

    PubMed

    Huang, Jian-Wen; Lv, Xiang-Guo; Li, Zhe; Song, Lu-Jie; Feng, Chao; Xie, Min-Kai; Li, Chao; Li, Hong-Bin; Wang, Ji-Hong; Zhu, Wei-Dong; Chen, Shi-Yan; Wang, Hua-Ping; Xu, Yue-Min

    2015-09-11

    The goal of this study was to evaluate the effects of urethral reconstruction with a three-dimensional (3D) porous bacterial cellulose (BC) scaffold seeded with lingual keratinocytes in a rabbit model. A novel 3D porous BC scaffold was prepared by gelatin sponge interfering in the BC fermentation process. Rabbit lingual keratinocytes were isolated, expanded, and seeded onto 3D porous BC. BC alone (group 1, N  =  10), 3D porous BC alone (group 2, N  =  10), and 3D porous BC seeded with lingual keratinocytes (group 3, N  =  10) were used to repair rabbit ventral urethral defects (2.0   ×   0.8 cm). Scanning electron microscopy revealed that BC consisted of a compact laminate while 3D porous BC was composed of a porous sheet buttressed by a dense outer layer. The average pore diameter and porosity of the 3D porous BC were 4.23   ±   1.14 μm and 67.00   ±   6.80%, respectively. At 3 months postoperatively, macroscopic examinations and retrograde urethrograms of urethras revealed that all urethras maintained wide calibers in group 3. Strictures were found in all rabbits in groups 1 and 2. Histologically, at 1 month postoperatively, intact epithelium occurred in group 3, and discontinued epithelium was found in groups 1 and 2. However, groups 2 and 3 exhibited similar epithelial regeneration, which was superior to that of group 1 at 3 months (p  <  0.05). Comparisons of smooth muscle content and endothelia density among the three groups revealed a significant increase at each time point (p  <  0.05). Our results demonstrated that 3D porous BC seeded with lingual keratinocytes enhanced urethral tissue regeneration. 3D porous BC could potentially be used as an optimized scaffold for urethral reconstruction.

  3. Rabbits killing birds revisited.

    PubMed

    Zhang, Jimin; Fan, Meng; Kuang, Yang

    2006-09-01

    We formulate and study a three-species population model consisting of an endemic prey (bird), an alien prey (rabbit) and an alien predator (cat). Our model overcomes several model construction problems in existing models. Moreover, our model generates richer, more reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rabbit or the cat when the bird is endangered. We confirm the existence of the hyperpredation phenomenon, which is a big potential threat to most endemic prey. Specifically, we show that, in an endemic prey-alien prey-alien predator system, eradication of introduced predators such as the cat alone is not always the best solution to protect endemic insular prey since predator control may fail to protect the indigenous prey when the control of the introduced prey is not carried out simultaneously.

  4. An Impedance-Based Model for the Assessment of Cardiopulmonary Function in Rabbits.

    PubMed

    Horsmon, Michael S; Vincelli, Nicole M; Taylor, James T; Kristovich, Robert L

    2016-03-01

    Improving the quality of physiologic data collected from research animals is most easily accomplished by collecting as much information as possible from a single subject, thereby reducing animal use and error associated with satellite groups. We investigated the feasibility of using a large-animal implantable telemetry device in New Zealand white rabbits (n = 6). The first task was to develop an implantation technique that yielded calibrated tidal volume (Vt) measurements that were within 10% of those obtained simultaneously from a pneumotachograph, a low-noise electrocardiogram, and stable blood pressure. The second task was to challenge implanted rabbits with the respiratory stimulant doxapram to assess linearity of the calibration across a range of Vt. Of the 3 electrode placements attempted, only one resulted in calibrations consistently below 10% error. Optimal electrode placement resulted in calibrated Vt measurements within 1.7% ± 0.3% of those obtained from a pneumotachograph during normal tidal breathing, 7.3% ± 0.7% of those after saline injection, and 6.0% ± 0.5% of those after doxapram injection. The Vt range was 9 to 15 mL for normal tidal breathing and saline injection and 25 to 30 mL after doxapram injection. Increases in mean arterial pressure of 25.0 ± 6.82 mm Hg and decreases in heart rate of 56.3 ± 6.82 bpm were associated with doxapram injection only. Our findings represent the first time that multiple cardiopulmonary endpoints have been assessed by telemetry in conscious, restrained rabbits. Whether animal position affects calibration accuracy warrants investigation.

  5. Progress in Dodecafluoropentane Emulsion as a Neuroprotective Agent in a Rabbit Stroke Model

    PubMed Central

    Woods, S.D.; Skinner, R.D.; Ricca, A.M.; Brown, A.T.; Lowery, J.D.; Borrelli, M.J.; Lay, J.O.; Culp, W.C.

    2013-01-01

    Introduction Dodecafluoropentane emulsion (DDFPe) in 250 nm nanodroplets seems to swell modestly to accept and carry large amounts of oxygen in the body at >29°C. Small particle size allows oxygen delivery even into hypoxic tissue unreachable by erythrocytes. Using permanent cerebral embolic occlusion in rabbits, we assessed DDFPe dose response as a neuroprotectant at 7 and 24 hours post-embolization without lysis of arterial obstructions and investigated blood pharmacokinetics. Methods New Zealand White rabbits (N=56) received cerebral angiography and embolic spheres (diameter=700-900 μm) occluded middle and/or anterior cerebral arteries. Intravenous DDFPe dosing (2% w/v emulsion) began at 60 minutes and repeated every 90 minutes until sacrifice at 7 or 24 hours post-embolization. Seven hour groups: 1) Control (embolized without treatment, N=6), and DDFPe treatment: 2) 0.1ml/kg (N=7), 3) 0.3ml/kg (N=9), 4) 0.6ml/kg (N=8). Twenty-four hour groups: 5) Control (N=16), and DDFPe treatment: 6) 0.1ml/kg (N=10). Infarcts as percent of total brain volume were determined using vital stains on brain sections. Other alert normal rabbits (N=8) received IV doses followed by rapid arterial blood sampling and GC-MS analysis. Results Percent infarct volume means significantly decreased for all DDFPe treated groups compared with controls, p=<0.004 to <0.03. Blood DDFP (gas) half-life was 1.45±0.17 minutes with R=0.958. Mean blood clearance was 78.5±24.9 ml/min/kg (mean±SE). Conclusions Intravenous DDFPe decreases ischemic stroke infarct volumes. Blood half-life values are very short. The much longer therapeutic effect, >90 minutes, suggests multiple compartments. Lowest effective dose and maximum effective therapy duration are not yet defined. Rapid development is warranted. PMID:23813100

  6. Docetaxel Inhibits Urethral Stricture Formation, an Initial Study in Rabbit Model

    PubMed Central

    Fu, Delai; Chong, Tie; Li, Hecheng; Zhang, Huibo; Wang, Ziming

    2014-01-01

    Introduction Urethral stricture, a frequent source of lower urinary tract disorders in men, is still a difficult problem for urologists. Based the anti-restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi-synthetic analogue of paclitaxel, in limiting urethral stricture formation was studied. Methods Forty adult New Zealand male rabbits were involved in this study, which were randomly assigned into 3 groups, namely a high dose docetaxel (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group, with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm-long circumferential electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Drugs were given by urethral irrigation daily and continuous for 28 days. Stricture formation was assessed by retrograde urethrography and videourethroscopy. Urethra pathology was evaluated by hematoxylin and eosin staining and Sirius red staining. Results At the end of this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group, respectively. Urethral diameters in DH, DL and C group were (7.17±1.63) mm, (6.55±0.62) mm, (3.23±1.36) mm, with a normal urethral diameter of (9.08±1.29) mm. Lumen reduction in DH, DL and C group were (36.93±11.58)%, (48.03±7.89)% and (84.66±14.95)%, respectively. Statistically difference could be found between every two groups (p<0.05) both in urethral diameters and in lumen reduction, except for compare of urethral diameters between DH and DL group. Histological examination confirmed mass fibrous tissue and collagen content at the stricture sit in C group, whereas less in docetaxel treated rabbits. Conclusions Docetaxel could limit urethral stricture formation, which may be due to inhibition of fibrous tissue and collagen expression. Docetaxel may become a new choice in the prevention of urethral stricture formation. PMID:25375859

  7. The prevention of prosthetic infection using a cross-linked albumin coating in a rabbit model.

    PubMed

    An, Y H; Bradley, J; Powers, D L; Friedman, R J

    1997-09-01

    We evaluated the effects of a serum protein coating on prosthetic infection in 29 adult male rabbits divided into three groups: control, albumin-coated and uncoated. We used 34 grit-blasted, commercially pure titanium implants. Eleven were coated with cross-linked albumin. All the implants were exposed to a suspension of Staphylococcus epidermidis before implantation. Our findings showed that albumin-coated implants had a much lower infection rate (27%) than the uncoated implants (62%). This may be a useful method of reducing the infection of prostheses.

  8. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  9. Poly(lactide-co-glycolide) Microspheres for MRI-Monitored Delivery of Sorafenib in a Rabbit VX2 model

    PubMed Central

    Chen, Jeane; White, Sarah B.; Harris, Kathleen R.; Li, Weiguo; Yap, Jonathan WT; Kim, Dong-Hyun; Lewandowski, Robert J.; Shea, Lonnie D.; Larson, Andrew C.

    2015-01-01

    Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 hours. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors. PMID:26022791

  10. Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study

    PubMed Central

    Zhang, Ruoxi; Chen, Shuyuan; Zhang, Hui; Liu, Qi; Xing, Jianpang; Zhao, Qi; Wang, Yu; Yu, Bo; Hou, Jingbo

    2016-01-01

    This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New Zealand White rabbits; the animals received a high-fat diet, beginning one week before stent implantation. Each animal was randomly assigned to 1 of 4 groups, receiving intravenous injections of either methotrexate (0.4 mg/kg) or placebo weekly for 4 or 12 weeks. Stented arterial segments were harvested after stenting for 4 or 12 weeks, and processed for OCT and histological analysis. Prior to harvesting the arterial segments, blood was collected for the determinations of cytokine levels. Compared with the control animals, the methotrexate-treated animals showed lower rates of lipid-rich intima and per-strut low-signal intensity layers, smaller neointimal areas, and reduced neointimal thickness; larger fibrous cap thicknesses and smaller lumen areas were also seen in the animals receiving methotrexate. The levels of serum interleukin, adhesion molecules, and nuclear factor-κB p65 decreased and IL-10 level increased in the methotrexate-treated animals. Targeting the pro-inflammatory pathways may be an effective way to prevent restenosis without the long-term risk of late thrombosis. PMID:27644847

  11. Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis

    PubMed Central

    Zhao, Xueqiang; Kong, Jing; Zhao, Yuxia; Wang, Xuping; Bu, Peili; Zhang, Cheng; Zhang, Yun

    2015-01-01

    We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways. PMID:26655882

  12. Evaluation of the chondroprotective effects of glucosamine and fish collagen peptide on a rabbit ACLT model using serum biomarkers.

    PubMed

    Ohnishi, Akihiro; Osaki, Tomohiro; Matahira, Yoshiharu; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

    2013-05-02

    The aim of this study was to investigate the correlations of severity of osteoarthritis (OA) and serum biomarkers including keratan sulfate (KS), hyaluronic acid (HA) and chondroitin sulfate (CS) 846 epitope. We also investigated the effect of glucosamine and fish collagen peptide (FCP) on OA. OA was induced in 12 rabbits (12 weeks of age) by anterior cruciate ligament transection (ACLT). After the surgery, the rabbits were orally administered FCP (F group), glucosamine (G group) or FCP and glucosamine (FG group) for 4 weeks. The control group was provided water ad libitum (C group). Blood was collected before surgery (pre-ACLT) and before euthanasia (post-ACLT) for serum marker measurement. Biomarker levels were measured by using commercial kits. We evaluated OA severity both macroscopically and histologically. Macroscopic evaluation showed mildly eroded condylar surfaces in the C group. Histological findings were significantly different from the FG and other groups. There were no significant differences between each group at post-ACLT in terms of serum KS, HA and CS 846. Histological assessment and serum biomarker measurements performed at post-ACLT showed a significant correlation between HA concentration and OA severity. Variations in the CS 846 concentration at pre-ACLT and post-ACLT were significantly correlated with OA severity. Administration of glucosamine and FCP had chondroprotective effects in the ACLT model. Serum biomarker concentrations were significantly correlated with cartilage injury. Serum biomarker measurement would be useful for monitoring articular cartilage damage in the clinical setting.

  13. In vivo testing of porous Ti-25Nb alloy serving as a femoral stem prosthesis in a rabbit model

    PubMed Central

    Weng, Xiaojun; Yang, Hailin; Xu, Jian; Li, Xiaosheng; Liao, Qiande; Wang, Jing

    2016-01-01

    The aim of the present study was to observe the performance of Ti-25Nb alloys with various porosities as femoral stem prostheses in a rabbit model, thus providing basic experimental evidence for the development of porous prostheses. The porous Ti-25Nb alloy prostheses were designed according to the morphology of the medullary cavity. These prostheses were placed into the femoral medullary cavities in 36 New Zealand white rabbits. Postoperative X-ray films, scanning electron microscopy (SEM) of the implant interface, energy-dispersive spectroscopy (EDS) analysis of the implant surface, pulling-out test and general observations were conducted. The specimens showed good biocompatibility; there was no obvious bone absorption in porous Ti-25Nb specimens with different porosities at different time points observed using X-ray films. Under SEM examination, calcium deposits were observed inside the pores and in the interface between bone and prostheses. The EDS analysis demonstrated that calcium deposits were present on the surface of the prostheses at the eight-week point postoperatively. The pulling-out test showed good bonding strength between bone and implant; after pulling out, the surface and inside the pores of the prostheses all presented bone mass. Porous Ti-25Nb alloy implants presents good biocompatibility as well as providing a biological fixation between the bone and implant. A porosity of 70% is more advantageous to the newborn bone ingrowth, combined with achieving a more solid bone-implant interface. PMID:27602063

  14. Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

    PubMed

    Cui, Xu; Huang, Wenhai; Zhang, Yadong; Huang, Chengcheng; Yu, Zunxiong; Wang, Lei; Liu, Wenlong; Wang, Ting; Zhou, Jie; Wang, Hui; Zhou, Nai; Wang, Deping; Pan, Haobo; Rahaman, Mohamed N

    2017-04-01

    There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml(-1) to 2.5gml(-1)). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery.

  15. NGF promotes hemodynamic recovery in a rabbit hindlimb ischemic model through trkA- and VEGFR2-dependent pathways.

    PubMed

    Karatzas, Andreas; Katsanos, Konstantinos; Lilis, Ioannis; Papadaki, Helen; Kitrou, Panagiotis; Lecht, Shimon; Marcinkiewicz, Cezary; Siablis, Dimitris; Lelkes, Peter I; Lazarovici, Philip; Tsopanoglou, Nikos E

    2013-09-01

    Nerve growth factor (NGF) has been reported to play an important role in physiological and pathological angiogenesis. Based on these observations, we hypothesized that NGF may induce the formation of functional blood vessels in a hindlimb ischemic rabbit model. Hindlimb ischemia was induced in 34 rabbits bilaterally by endovascular embolization of femoral arteries. On the 7th, 14th, and 20th postembolization days, NGF was injected intramuscularly, in 1 ischemic limb, and vehicle was injected in the contralateral control limb. On the 40th day, newly developed collateral vessels (diameter >500 μm) were quantified by transauricular intraarterial subtraction angiography. Perfusion analysis of an in vivo dynamic computed tomography study was performed to the limbs to investigate the hemodynamic recovery of the distal ischemic tissues. Functional estimation of limb perfusion showed a statistically significant increase of blood flow and blood volume for NGF. However, the increase of the collateral vessels was not detectable angiographically, providing evidence for the existence of a NGF-stimulated capillary angiogenic network but not increase of arteriogenesis. The combination of NGF with either tropomyosin-related kinase type A or vascular endothelial growth factor receptor 2 antagonists abolished the NGF-induced hemodynamic recovery. These findings provide new insights into understanding the involvement of NGF in vascular formation and its applications in therapeutic angiogenesis.

  16. Long-Term In Vivo Electromechanical Reshaping for Auricular Reconstruction in the New Zealand White Rabbit Model

    PubMed Central

    Badran, Karam W.; Manuel, Cyrus T.; Loy, Anthony Chin; Conderman, Christian; Yau, Yuk Yee; Lin, Jennifer; Tjoa, Tjoson; Su, Erica; Protsenko, Dmitriy; Wong, Brian J. F.

    2016-01-01

    Objectives/Hypothesis To demonstrate the dosimetry effect of electromechanical reshaping (EMR) on cartilage shape change, structural integrity, cellular viability, and remodeling of grafts in an in vivo long-term animal model. Study Design Animal study. Methods A subperichondrial cartilaginous defect was created within the base of the pinna of 31 New Zealand white rabbits. Autologous costal cartilage grafts were electromechanically reshaped to resemble the rabbit auricular base framework and mechanically secured into the pinna base defect. Forty-nine costal cartilage specimens (four control and 45 experimental) successfully underwent EMR using a paired set of voltage-time combinations and survived for 6 or 12 weeks. Shape change was measured, and specimens were analyzed using digital imaging, tissue histology, and confocal microscopy with LIVE-DEAD viability assays. Results Shape change was proportional to charge transfer in all experimental specimens (P <.01) and increased with voltage. All experimental specimens contoured to the auricular base. Focal cartilage degeneration and fibrosis was observed where needle electrodes were inserted, ranging from 2.2 to 3.9 mm. The response to injury increased with increasing charge transfer and survival duration. Conclusions EMR results in appropriate shape change in cartilage grafts with chondrocyte injury highly localized. These studies suggest that elements of auricular reconstruction may be feasible using EMR. Extended survival periods and further optimization of voltage-time pairs are necessary to evaluate the long-term effects and shape-change potential of EMR. PMID:25779479

  17. Opuntia Extract Reduces Scar Formation in Rabbit Ear Model: A Randomized Controlled Study.

    PubMed

    Fang, Quan; Huang, Chunlan; You, Chuangang; Ma, Shaolin

    2015-12-01

    The purpose of this article is to investigate the effect of Opuntia stricta H (Cactaceae) extract on suppression of hypertrophic scar on ventral surface wounds of rabbit ears. Full thickness skin defection was established in a rabbit ear to simulate hypertrophic scar. Opuntia extract was sprayed on the wounds in the experimental group, and normal saline was used in the control group. After the wounds healed with scar formation, the hypertrophic scar tissue was harvested on days 22, 39, and 54 for histological analysis. The expression of type I and type III collagen and matrix metalloproteinase-1 (MMP-1) were evaluated by immunohistochemistry and real-time quantitative polymerase chain reaction. The results indicated that the scar of the control group is more prominent compared with the opuntia extract group. The expression of type I collagen in the opuntia extract group was lower than the control group, while type III collagen in opuntia extract group gradually increased and exceeded control group. The expression of MMP-1 decreased in the opuntia extract group, while the control group increased over time, but the amount of MMP-1 was much higher than that in the control group on day 22. In conclusion, opuntia extract reduces hypertrophic scar formation by means of type I collagen inhibition, and increasing type III collagen and MMP-1.T he novel application of opuntia extract may lead to innovative and effective antiscarring therapies.

  18. Percutaneous cartilage injection: A prospective animal study on a rabbit model

    PubMed Central

    2013-01-01

    Background Cartilage grafting is a useful technique in nasal reconstruction. Implantation of a whole graft is usually done through an incision. Crushed cartilage can also be used. Injection of cartilage could be an alternative to implantation. The objective of this study is to compare the long-term viability of percutaneously injected crushed auricular cartilage to surgically implanted cartilage in the rabbit. Methods Auricular cartilage was harvested bilaterally in 10 New Zealand white rabbits. A 1 cm2 cartilage graft was implanted surgically on the upper nasal dorsum. The remaining cartilage was crushed and percutaneously injected on the lower nasal dorsum. Volume and mass of each graft were compared between pre-implantation and after 3 months of observation. A histological study was conducted to evaluate chondrocyte viability and degree of fibrosis on pre and post-implantation cartilage. Results Mass and volume remained similar for surgically implanted cartilage grafts. Mass and volume diminished by an average of 47% and 40% respectively after 3 months for the injected crushed cartilage grafts. Chondrocyte viability was an average of 25% lower in the injected grafts. Conclusions Cartilage injection is a promising technique that must be refined to increase chondrocyte viability. Developing an appropriate injection apparatus would improve this technique. PMID:23663241

  19. A Novel Technique for Conjunctivoplasty in a Rabbit Model: Platelet-Rich Fibrin Membrane Grafting

    PubMed Central

    Çakmak, Hasan Basri; Dereli Can, Gamze; Ünverdi, Hatice; Toklu, Yasin; Hücemenoğlu, Sema

    2016-01-01

    Purpose. To investigate the effect of platelet-rich fibrin (PRF) membrane on wound healing. Methods. Twenty-four right eyes of 24 New Zealand rabbits equally divided into 2 groups for the study design. After the creation of 5 × 5 mm conjunctival damage, it was secured with PRF membrane, which was generated from the rabbit's whole blood samples in PRF membrane group, whereas damage was left unsutured in the control group. Three animals were sacrificed in each group on the 1st, 3rd, 7th, and 28th postoperative days. Immunohistochemical (IHC) stainings and biomicroscopic evaluation were performed and compared between groups. Results. PRF membrane generated significant expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and platelet-derived growth factor (PDGF) in the early postoperative period. However, the IHC evaluation allowed showing the excessive staining at day 28, in control group. Biomicroscopic evaluation revealed complete epithelialization in PRF membrane group, but none of the cases showed complete healing in the control group. Conclusions. This experimental study showed us the beneficial effects of the PRF membrane on conjunctival healing. Besides its chemical effects, it provides mechanical support as a scaffold for the migrating cells that are important for ocular surface regeneration. These overall results encourage us to apply autologous PRF membrane as a growth factor-enriched endogenous scaffold for ocular surface reconstruction. PMID:27747098

  20. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  1. Study of wound-healing activity of bioregulators isolated from eye tissues and bovine serum in the model of experimental corneal injury in rabbits in vivo.

    PubMed

    Konstantinovsky, A A; Krasnov, M S; Yamskova, V P; Rybakova, E Yu; Yamskov, I A

    2012-06-01

    We compared wound-healing activity of bioregulators isolated from cattle cornea, serum, and retinal pigment epithelium on in vivo model of experimental corneal injury in rabbits. Bioregulators were instilled into the eye as solutions at a concentration corresponding to 10(-12) mg protein/ml. The animals were sacrificed on day 21 after injury and the corneas were examined histologically. The best wound-healing effect was produced by bioregulators isolated from the cornea and serum and instilled successively into rabbit eyes with an interval of 15-20 min twice a day: multicellular epithelium was observed in the wound, and slight inflammation, in the stroma.

  2. On Studying the Interaction Between Different Stent Models and Rabbit Tracheal Tissue: Numerical, Endoscopic and Histological Comparison.

    PubMed

    Chaure, J; Serrano, C; Fernández-Parra, R; Peña, E; Lostalé, F; De Gregorio, M A; Martínez, M A; Malvè, M

    2016-02-01

    Stenting technique is employed worldwide for treating atherosclerotic vessel and tracheal stenosis. Both diseases can be treated by means of metallic stents which present advantages but are affected by the main problem of restenosis of the stented area. In this study we have built a rabbit trachea numerical model and we have analyzed it before and after insertion and opening of two types of commercial stent: a Zilver(®) Flex™ Stent and a WallStent™. In experimental parallel work, two types of stent were implanted in 30 New Zealand rabbits divided in two groups of 10 animals corresponding to each stent type and a third group made up of 10 animals without stent. The tracheal wall response was assessed by means of computerized tomography by endoscopy, macroscopic findings and histopathological study 90 days after stent deployment. Three idealized trachea models, one model for each group, were created in order to perform the computational study. The animal model was used to validate the numerical findings and to attempt to find qualitative correlations between numerical and experimental results. Experimental findings such as inflammation, granuloma and abnormal tissue growth, assessed from histomorphometric analyses were compared with derived numerical parameters such as wall shear stress (WSS) and maximum principal stress. The direct comparison of these parameters and the biological response supports the hypothesis that WSS and tensile stresses may lead to a greater tracheal epithelium response within the stented region, with the latter seeming to have the dominant role. This study may be helpful for improving stent design and demonstrates the feasibility offered by in-silico investigated tracheal structural and fluid dynamics.

  3. Assessment of glenoid chondral healing: comparison of microfracture to autologous matrix-induced chondrogenesis in a novel rabbit shoulder model

    PubMed Central

    Wang, Vincent M.; Karas, Vasili; Lee, Andrew S.; Yin, Ziying; Van Thiel, Geoffrey S.; Hussey, Kristen; Sumner, D. Rick; Chubinskaya, Susan; Magin, Richard L.; Verma, Nikhil N.; Romeo, Anthony A.; Cole, Brian J.

    2015-01-01

    Background Management of glenohumeral arthrosis in young patients is a considerable challenge, with a growing need for non-arthroplasty alternatives. The objectives of this study were to develop an animal model to study glenoid cartilage repair and to compare surgical repair strategies to promote glenoid chondral healing. Methods Forty-five rabbits underwent unilateral removal of the entire glenoid articular surface and were divided into 3 groups—duntreated defect (UD), microfracture (MFx), and MFx plus type I/III collagen scaffold (autologous matrix-induced chondrogenesis [AMIC])—for the evaluation of healing at 8 weeks (12 rabbits) and 32 weeks (33 rabbits) after injury. Contralateral shoulders served as unoperated controls. Tissue assessments included 11.7-T magnetic resonance imaging (long-term healing group only), Equilibrium Partitioning of an Ionic Contrast agent via microcomputed tomography (EPIC-μCT), and histologic investigation (grades on International Cartilage Repair Society II scoring system). Results At 8 weeks, x-ray attenuation, thickness, and volume did not differ by treatment group. At 32 weeks, the T2 index (ratio of T2 values of healing to intact glenoids) was significantly lower for the MFx group relative to the AMIC group (P = .01) whereas the T1ρ index was significantly lower for AMIC relative to MFx (P = .01). The micro–computed tomography–derived repair tissue volume was significantly higher for MFx than for UD. Histologic investigation generally suggested inferior healing in the AMIC and UD groups relative to the MFx group, which exhibited improvements in both integration of repair tissue with subchondral bone and tidemark formation over time. Discussion Improvements conferred by AMIC were limited to magnetic resonance imaging outcomes, whereas MFx appeared to promote increased fibrous tissue deposition via micro–computed tomography and more hyaline-like repair histologically. The findings from this novel model suggest that

  4. USE OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS TO ASSESS POLLUTANT-INDUCED LUNG CHANGES IN AN ANIMAL MODEL OF CARDIOVASCULAR (CV) DISEASE.

    EPA Science Inventory

    Animal models of coronary heart disease (e.g., hyperlipidemic rabbits) are being used to investigate epidemiologic associations between higher levels of air pollution and adverse CV consequences. Mechanisms by which pollutant-induced lung or systemic inflammation leads to acute C...

  5. A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

    SciTech Connect

    Fichorova, Raina N.; Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan; Chandra, Neelima; Doncel, Gustavo F.

    2015-06-15

    Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were

  6. Grepafloxacin against penicillin-resistant pneumococci in the rabbit meningitis model.

    PubMed

    Gerber, C M; Tovar, L; Cottagnoud, M; Neftel, K A; Täuber, M G; Cottagnoud, P

    2000-08-01

    Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L) (triangle uplog(10) cfu/mL*h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg iv; triangle uplog(10) cfu/mL*h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20 mg/kg iv; triangle uplog(10) cfu/mL*h for ceftriaxone, -0.32 +/- 0. 12; dose, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin showed synergic activity.

  7. Antioxidation Effect of Simvastatin in Aorta and Hippocampus: A Rabbit Model Fed High-Cholesterol Diet

    PubMed Central

    Zhang, Guangyin; Li, Ming; Xu, Yinzhi; Peng, Li; Yang, Cui; Zhou, Yanan; Zhang, Junping

    2016-01-01

    We show that hypercholesterolemia contributes to oxidative stress injury progression in brain and simvastatin counteracts the cholesterol-induced peroxidation injury in rabbit hippocampus, and we demonstrate for the first time that the simvastatin is a critical role in brain protection and identify HO-1 and other related antioxidant enzymes as molecular target for active redox compounds. Second, our experiments have pointed out an association between statin treatment and a decrease in the risk of having peroxidation damage of brain. The balance effects of simvastatin to ROS and antioxidants enzymes network are most probably due to improved SOD functional activity, increase in GSH-Px, increase in HO-1 expression, and decrease of MDA generation. PMID:26798426

  8. Imaging the Efficacy of Anti-Inflammatory Liposomes in a Rabbit Model of Atherosclerosis by Non-Invasive Imaging

    PubMed Central

    Lobatto, Mark E.; Calcagno, Claudia; Metselaar, Josbert M.; Storm, Gert; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J. M.

    2013-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques. PMID:22449928

  9. Imaging the efficacy of anti-inflammatory liposomes in a rabbit model of atherosclerosis by non-invasive imaging.

    PubMed

    Lobatto, Mark E; Calcagno, Claudia; Metselaar, Josbert M; Storm, Gert; Stroes, Erik S G; Fayad, Zahi A; Mulder, Willem J M

    2012-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques.

  10. Effect of nonablative laser energy on joint capsular properties: an in-vitro study using a rabbit model

    NASA Astrophysics Data System (ADS)

    Hayashi, Kei; Markel, Mark D.; Thabit, George, III; Bogdanske, John J.; Thielke, Robert J.; Cooley, A. J.; Vailas, Arthur C.; Mascio, Laura N.; Vanderby, Ray, Jr.

    1996-05-01

    Recent scientific studies evaluating laser energy for tissue welding and thermokeratoplasty have demonstrated that the application of laser energy at non-ablative levels can alter collagen's structural and biochemical properties. A recent pilot study has demonstrated that the non-ablative application of holmium: yttrium-aluminum-garnet (Ho:YAG) laser energy to the joint capsule of patients with glenohumeral instability shrank the joint capsule, stabilizing the shoulder in the majority of the patients treated. Based on the collective findings of these studies, we hypothesized that thermal modification of dense collagenous tissues such as joint capsule, ligament, and tendon can be achieved by applying non-ablative laser energy. The purpose of this study was to evaluate the effect of laser energy at non-ablative levels on joint capsular mechanical, biochemical, histological, and ultrastructural properties in an in vitro rabbit model.

  11. Recombinant nAG (a salamander-derived protein) decreases the formation of hypertrophic scarring in the rabbit ear model.

    PubMed

    Al-Qattan, Mohammad M; Abd-Al Wahed, Mervat M; Hawary, Khalid; Alhumidi, Ahmed A; Shier, Medhat K

    2014-01-01

    nAG (newt-Anterrior Gradient) protein is the key mediator of regrowth of amputated limbs in salamanders. In a previous work in our lab, a new nAG gene (suitable for humans) was designed and cloned. The cloned vector was transfected into primary human fibroblasts. The expression of nAG in human primary fibroblasts was found to suppress collagen expression. The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model. This is associated with lower scar elevation index (SEI), lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls.

  12. Submillimeter Diameter Poly(Vinyl Alcohol) Vascular Graft Patency in Rabbit Model

    PubMed Central

    Cutiongco, Marie F. A.; Kukumberg, Marek; Peneyra, Jonnathan L.; Yeo, Matthew S.; Yao, Jia Y.; Rufaihah, Abdul Jalil; Le Visage, Catherine; Ho, Jackie Pei; Yim, Evelyn K. F.

    2016-01-01

    Microvascular surgery is becoming a prevalent surgical practice. Replantation, hand reconstruction, orthopedic, and free tissue transfer procedures all rely on microvascular surgery for the repair of venous and arterial defects at the millimeter and submillimeter levels. Often, a vascular graft is required for the procedure as a means to bridge the gap between native arteries. While autologous vessels are desired for their bioactivity and non-thrombogenicity, the tedious harvest process, lack of availability, and caliber or mechanical mismatch contribute to graft failure. Thus, there is a need for an off-the-shelf artificial vascular graft that has low thrombogenic properties and mechanical properties matching those of submillimeter vessels. Poly(vinyl alcohol) hydrogel (PVA) has excellent prospects as a vascular graft due to its bioinertness, low thrombogenicity, high water content, and tunable mechanical properties. Here, we fabricated PVA grafts with submillimeter diameter and mechanical properties that closely approximated those of the rabbit femoral artery. In vitro platelet adhesion and microparticle release assay verified the low thrombogenicity of PVA. A stringent proof-of-concept in vivo test was performed by implanting PVA grafts in rabbit femoral artery with multilevel arterial occlusion. Laser Doppler measurements indicated the improved perfusion of the distal limb after implantation with PVA grafts. Moreover, ultrasound Doppler and angiography verified that the submillimeter diameter PVA vascular grafts remained patent for 2 weeks without the aid of anticoagulant or antithrombotics. Endothelial cells were observed in the luminal surface of one patent PVA graft. The advantageous non-thrombogenic and tunable mechanical properties of PVA that are retained even in the submillimeter diameter dimensions support the application of this biomaterial for vascular replacement in microvascular surgery. PMID:27376059

  13. In vivo imaging in the rabbit as a model for the study of ovulation-inducing factors.

    PubMed

    Cervantes, M P; Palomino, J M; Adams, G P

    2015-01-01

    The study of factors responsible for eliciting ovulation in rabbits has been hampered by the lack of a suitable method of monitoring the ovaries in vivo. Ovarian imaging by ultrasound biomicroscopy was used in two experiments designed to determine the effects of seminal plasma on the ovulatory response in rabbits. In Experiment 1, female rabbits were group-housed and treated intramuscularly with saline, gonadotropin releasing hormone (GnRH), or seminal plasma of llamas or rabbits (n = 4 to 6 per group). Rabbits were euthanized eight days later to evaluate the ovarian response by ultrasound biomicroscopy ex situ. No differences among groups were detected in the proportion of rabbits that ovulated or in the number and size of corpora lutea. The high incidence of ovulation in the negative control group was unexpected, and confounded determination of an ovulation-inducing effect of seminal plasma. In Experiment 2, female rabbits were caged individually, and treated as in Experiment 1 (n = 5 to 7 per group). The ovarian response was evaluated in vivo by transcutaneous ultrasound biomicroscopy. Ovulation and formation of corpora lutea were detected only in rabbits given GnRH. A preovulatory surge in plasma luteinizing hormone concentration and a post-ovulatory rise in plasma progesterone concentration were detected only in rabbits treated with GnRH. Surgical translocation of the ovaries to a subcutaneous position enabled longitudinal assessment of the ovulatory response by ultrasound biomicroscopy. Results clearly documented the effect of physical/social interaction on ovulation in rabbits, and did not support the hypothesis that seminal plasma elicits ovulation in rabbits.

  14. Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

    PubMed

    Keswani, Sundeep G; Balaji, Swathi; Katz, Anna B; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles; Crombleholme, Timothy M

    2015-03-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal-fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of

  15. Daily exposure to summer circadian cycles affects spermatogenesis, but not fertility in an in vivo rabbit model.

    PubMed

    Sabés-Alsina, Maria; Planell, Núria; Torres-Mejia, Elen; Taberner, Ester; Maya-Soriano, Maria José; Tusell, Llibertat; Ramon, Josep; Dalmau, Antoni; Piles, Miriam; Lopez-Bejar, Manel

    2015-01-15

    Heat stress (HS) in mammals is a determining factor in the deterioration of spermatogenesis and can cause infertility. The aim of this study was to evaluate the effect of continuous summer circadian cycles on semen production, sperm cell features, fertility, prolificacy, and fecal cortisol metabolites from rabbits kept under an in vivo HS model. We split randomly 60 New Zealand White rabbits into two temperature-controlled rooms: The control group was maintained at comfort temperature (18 °C-22 °C) and an HS group, where the environmental temperature was programmed to increase from 22 °C to 31 °C and be maintained for 3 hours to this temperature at the central part of the day. Fecal cortisol metabolites were assessed to evaluate the stress conditions. Seminal parameters were analyzed. Although animals exposed to HS showed higher values of fecal cortisol metabolites (P = 0.0003), no differences were detected in fertility or prolificacy. Semen samples from HS males showed a significant decrease (P < 0.05) with respect to the controls in the percentage of viable spermatozoa (80.71% vs. 74.21%), and a significant (P ≤ 0.01) increase in the percentage of acrosomic abnormalities (22.57% vs. 36.96%) and tailless spermatozoa (7.91% vs. 12.83). Among motility parameters, no differences were found. This study describes a model of HS simulating a continuous summer daily cycle that allows periods of time to recover as it occurs under natural conditions. Although negative effects have been detected in several sperm parameters, fertility and prolificacy were not affected, suggesting a recovery of the reproductive function when normal conditions are reestablished.

  16. A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation.

    PubMed

    Fichorova, Raina N; Mendonca, Kevin; Yamamoto, Hidemi S; Murray, Ryan; Chandra, Neelima; Doncel, Gustavo F

    2015-06-15

    Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV+2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P<0.05), and decreased levels of TLR2 (P<0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P<0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product.

  17. Dynamic contrast-enhanced x-ray CT measurement of cerebral blood volume in a rabbit tumor model

    NASA Astrophysics Data System (ADS)

    Cenic, Aleksa; Lee, Ting-Yim; Craen, Rosemary A.; Gelb, Adrian W.

    1998-07-01

    Cerebral blood volume (CBV) is a major determinant of intracranial pressure (ICP). Hyperventilation is commonly employed to reduce raised ICP (e.g. in brain tumour patients) presumably through its effect on CBV. With the advent of slip- ring CT scanners, dynamic contrast-enhanced imaging allows for the measurement of CBV with high spatial resolution. Using a two-compartment model to characterize the distribution of X- ray contrast agent in the brain, we have developed a non- equilibrium CT method to measure CBV in normal and pathological regions. We used our method to investigate the effect of hyperventilation on CBV during propofol anaesthesia in rabbits with implanted brain tumours. Eight New Zealand White rabbits with implanted VX2 carcinoma brain tumours were studied. For each rabbit, regional CBV measurements were initially made at normocapnia (PaCO2 40 mmHg) and then at hyperventilation (PaCO2 25 mmHg) during propofol anaesthesia. The head was positioned such that a coronal image through the brain incorporated a significant cross-section of the brain tumour as well as a radial artery in a forelimb. Images at the rate of 1 per second were acquired for 2 minutes as Omnipaque 300 (1.5 ml/kg rabbit weight) was injected via a peripheral vein. In these CT images, regions of interest in the brain tissue (e.g. tumour, contra-lateral normal, and peri-tumoural) and the radial artery were drawn. For each region, the mean CT number in pre-contrast images was subtracted from the mean CT number in post-contrast images to produce either the tissue contrast concentration curve, or the arterial contrast concentration curve. Using our non- equilibrium analysis method based on a two-compartment model, regional CBV values were determined from the measured contrast concentration curves. From our study, the mean CBV values [+/- SD] in the tumour, peri-tumoural, and contra-lateral normal regions during normocapnia were: 5.47 plus or minus 1.97, 3.28 plus or minus 1.01, and 1

  18. Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

    SciTech Connect

    Lysitsas, Dimitrios N.; Katsouras, Christos S.; Papakostas, John C.; Toumpoulis, Ioannis K.; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G.; Seferiadis, Konstantin; Psychoyios, Nikolaos; Frillingos, Stathis; Pavlidis, Nikolaos; Marinos, Euaggelos; Khaldi, Lubna; Sideris, Dimitris A.; Michalis, Lampros K.

    2007-11-15

    Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 {+-} 0.0025 {mu}M (31 {+-} 1 {mu}g; low dose; n = 7), 0.55 {+-} 0.02 {mu}M (216 {+-} 8 {mu}g; high dose; n = 6), and 4.55 {+-} 0.1 {mu}M (1774 {+-} 39 {mu}g; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

  19. Antirestenotic effects of a novel polymer-coated d-24851 eluting stent. Experimental data in a rabbit iliac artery model.

    PubMed

    Lysitsas, Dimitrios N; Katsouras, Christos S; Papakostas, John C; Toumpoulis, Ioannis K; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G; Seferiadis, Konstantin; Psychoyios, Nikolaos; Frillingos, Stathis; Pavlidis, Nikolaos; Marinos, Euaggelos; Khaldi, Lubna; Sideris, Dimitris A; Michalis, Lampros K

    2007-01-01

    Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (DL: -lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 +/- 0.0025 microM (31 +/- 1 mug; low dose; n = 7), 0.55 +/- 0.02 microM (216 +/- 8 mug; high dose; n = 6), and 4.55 +/- 0.1 microM (1774 +/- 39 mug; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

  20. The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia

    PubMed Central

    Salgado-Pabon, Wilmara; Meyerholz, David K.; White, Mark J.; Schlievert, Patrick M.

    2016-01-01

    ABSTRACT The Spl proteases are a group of six serine proteases that are encoded on the νSaβ pathogenicity island and are unique to Staphylococcus aureus. Despite their interesting biochemistry, their biological substrates and functions in virulence have been difficult to elucidate. We found that an spl operon mutant of the community-associated methicillin-resistant S. aureus USA300 strain LAC induced localized lung damage in a rabbit model of pneumonia, characterized by bronchopneumonia observed histologically. Disease in the mutant-infected rabbits was restricted in distribution compared to that in wild-type USA300-infected rabbits. We also found that SplA is able to cleave the mucin 16 glycoprotein from the surface of the CalU-3 lung cell line, suggesting a possible mechanism for wild-type USA300 spreading pneumonia to both lungs. Investigation of the secreted and surface proteomes of wild-type USA300 and the spl mutant revealed multiple alterations in metabolic proteins and virulence factors. This study demonstrates that the Spls modulate S. aureus physiology and virulence, identifies a human target of SplA, and suggests potential S. aureus targets of the Spl proteases. IMPORTANCE Staphylococcus aureus is a versatile human pathogen that produces an array of virulence factors, including several proteases. Of these, six proteases called the Spls are the least characterized. Previous evidence suggests that the Spls are expressed during human infection; however, their function is unknown. Our study shows that the Spls are required for S. aureus to cause disseminated lung damage during pneumonia. Further, we present the first example of a human protein cut by an Spl protease. Although the Spls were predicted not to cut staphylococcal proteins, we also show that an spl mutant has altered abundance of both secreted and surface-associated proteins. This work provides novel insight into the function of Spls during infection and their potential ability to degrade

  1. Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model

    PubMed Central

    Zhang, Lin; Liu, Feng-Yong; Fu, Jin-Xin; Duan, Feng; Fan, Qing-Sheng; Wang, Mao-Qiang

    2014-01-01

    Aim: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model. Methods: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry. Results: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment. Conclusion: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC. PMID:25550815

  2. Evaluation of the rabbit as a model for Chagas disease-II. Histopathologic studies of the heart, digestive tract and skeletal muscle.

    PubMed

    da Silva, A M; Eduardo Ramirez, L; Vargas, M; Chapadeiro, E; Brener, Z

    1996-01-01

    In order to investigate the value of the rabbit as an experimental model for Chagas' disease, seventy one animals were inoculated with different Trypanosoma cruzi strains and routes. The rabbits were submitted to necropsy in acute (earlier than three months of infection), recent chronic (three to six months) and late chronic (later than six months) phases. Myocarditis, generally focal and endomysial, occurred in 94.1%, 66.7% and 70.8% of the infected rabbits respectively in the acute, recent chronic and late chronic phases. The myocardial inflammatory exudate was composed by mononuclear cells, and also polymorphonuclear cells in the acute phase. In most cases of the late chronic phase, the myocarditis was similar to that described in the indeterminate form of human chagasic patients. Initial fibrosis occurred in the three phases but was more severe and frequent in the early chronic. Advanced fibrosis occurred only in the late chronic phase. Tissue parasites occurred only in the acute phase. The digestive tract and skeletal muscles showed mild and occasional lesions. Our data indicate that experimentally infected chagasic rabbits repeat some lesions similar to that of humans chagasic patients, specially that of the indeterminate form. So, it may be a useful, however not an ideal, model.

  3. Hemodynamic Changes Caused by Flow Diverters in Rabbit Aneurysm Models: Comparison of Virtual and Realistic FD Deployments Based on Micro-CT Reconstruction.

    PubMed

    Xu, Jinyu; Deng, Benqiang; Fang, Yibin; Yu, Ying; Cheng, Jiyong; Wang, Shengzhang; Wang, Kuizhong; Liu, Jian-Min; Huang, Qinghai

    2013-01-01

    Adjusting hemodynamics via flow diverter (FD) implantation is emerging as a novel method of treating cerebral aneurysms. However, most previous FD-related hemodynamic studies were based on virtual FD deployment, which may produce different hemodynamic outcomes than realistic (in vivo) FD deployment. We compared hemodynamics between virtual FD and realistic FD deployments in rabbit aneurysm models using computational fluid dynamics (CFD) simulations. FDs were implanted for aneurysms in 14 rabbits. Vascular models based on rabbit-specific angiograms were reconstructed for CFD studies. Real FD configurations were reconstructed based on micro-CT scans after sacrifice, while virtual FD configurations were constructed with SolidWorks software. Hemodynamic parameters before and after FD deployment were analyzed. According to the metal coverage (MC) of implanted FDs calculated based on micro-CT reconstruction, 14 rabbits were divided into two groups (A, MC >35%; B, MC <35%). Normalized mean wall shear stress (WSS), relative residence time (RRT), inflow velocity, and inflow volume in Group A were significantly different (P<0.05) from virtual FD deployment, but pressure was not (P>0.05). The normalized mean WSS in Group A after realistic FD implantation was significantly lower than that of Group B. All parameters in Group B exhibited no significant difference between realistic and virtual FDs. This study confirmed MC-correlated differences in hemodynamic parameters between realistic and virtual FD deployment.

  4. Characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in New Zealand white rabbits as a trigger for treatment.

    PubMed

    Comer, Jason E; Ray, Bryan D; Henning, Lisa N; Stark, Gregory V; Barnewall, Roy E; Mott, Jason M; Meister, Gabriel T

    2012-09-01

    The development of an appropriate animal therapeutic model is essential to assess the potential efficacy of therapeutics for use in the event of a Bacillus anthracis exposure. We conducted a natural history study that showed New Zealand White rabbits exhibited a significant increase in body temperature (SIBT), changes in hematologic parameters, and increases in C-reactive protein and succumbed to disease with an average time to death of approximately 73 h following aerosol challenge with B. anthracis Ames spores. The SIBT was used as a trigger to treat with a fully human monoclonal antibody directed at protective antigen (PA). Ninety percent (9/10) of the treated rabbits survived the lethal inhalational challenge of B. anthracis. Further characterization investigated the protective window of opportunity for anti-PA antibody administration up to 12 h post-onset of SIBT. Eighty-three percent (5/6) of the rabbits treated at SIBT and 100% (6/6) of those treated at 6 h after SIBT survived challenge. Only 67% (4/6) of the rabbits treated at 12 h after SIBT survived. The increase in body temperature corresponded with both bacteremia and antigenemia (PA in the blood), indicating that SIBT is a suitable trigger to initiate treatment in a therapeutic model of inhalational anthrax.

  5. Effect of Leukocyte-Rich and Platelet-Rich Plasma on Healing of a Horizontal Medial Meniscus Tear in a Rabbit Model.

    PubMed

    Shin, Kyun Ho; Lee, Haseok; Kang, Seonghyun; Ko, You-Jin; Lee, Seung-Yup; Park, Jung-Ho; Bae, Ji-Hoon

    2015-01-01

    There are limited reports on the effect of platelet-rich plasma (PRP) on meniscus healing. The purpose of this study was to investigate the effect of leukocyte-rich PRP (L-PRP) on potential healing of the horizontal medial meniscus tears in a rabbit model. A horizontal medial meniscus tear was created in both knees of nine skeletally mature adult rabbits. Left or right knees were randomly assigned to a L-PRP group, or a control group. 0.5 mL of L-PRP from 10 mL of each rabbit's whole blood was prepared and injected into the horizontal tears in a L-PRP group. None was applied to the horizontal tears in a control group. The histological assessment of meniscus healing was performed at two, four, and six weeks after surgery. We found that there were no significant differences of quantitative histologic scoring between two groups at 2, 4, and 6 weeks after surgery (p > 0.05). This study failed to show the positive effect of single injection of L-PRP on enhancing healing of the horizontal medial meniscus tears in a rabbit model. Single injection of L-PRP into horizontal meniscus tears may not effectively enhance healing of horizontal medial meniscus tears.

  6. Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model

    PubMed Central

    Parhi, Rabinarayan; Suresh, Padilam

    2015-01-01

    The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm2/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance. PMID:27222758

  7. Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a Rabbit Model of Atherothrombosis

    PubMed Central

    Hua, Ning; Baik, Fred; Pham, Tuan; Phinikaridou, Alkystis; Giordano, Nick; Friedman, Beth; Whitney, Michael; Nguyen, Quyen T.; Tsien, Roger Y.; Hamilton, James A.

    2015-01-01

    Introduction The detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture. Methods and Results In an atherothrombotic rabbit model, disrupted plaques were identified with in vivo MRI and co-registered in the same rabbit aorta with the in vivo uptake of ACPPs, cleaved by matrix metalloproteinases (MMPs) or thrombin. ACPP uptake, mapped ex vivo in whole aortas, was higher in disrupted compared to non-disrupted plaques. Specifically, disrupted plaques demonstrated a 4.5~5.0 fold increase in fluorescence enhancement, while non-disrupted plaques showed only a 2.2~2.5 fold signal increase. Receiver operating characteristic (ROC) analysis indicates that both ACPPs (MMP and thrombin) show high specificity (84.2% and 83.2%) and sensitivity (80.0% and 85.7%) in detecting disrupted plaques. The detection power of ACPPs was improved when combined with the MRI derived measure, outward remodeling ratio. Conclusions Our targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout. PMID:26448434

  8. Single vs. double layer suturing method repair of the urethral plate in the rabbit model of hypospadias

    PubMed Central

    Shirazi, Mehdi; Rahimi, Mohammad

    2016-01-01

    Introduction There are different methods of urethroplasty in hypospadias. The present study aimed to compare the repair of the urethral plate by single vs. double layer suturing. Material and methods Fifteen male rabbits were assigned to the control, single layer, and double layer urethral plate suturing groups (n = 5). Experimental hypospadias was induced in the second and third groups and the urethral plates were sutured. After two weeks, the penis was dissected out and underwent histopathological processing. Stereological studies were applied to obtain quantitative histological data regarding the structure of the urethra and the related part of the corpus spongiosum. Results Volume density of the urethral epithelium (the fraction of unit volume of the urethra occupied by its epithelium) was higher in the single layer suturing group when compared to the double layer or control groups (p <0.01). Additionally, the volume density of the urethral lumen (the fraction of the corpus spongiosum that is occupied by the urethral lumen) in the single versus the double layer suturing groups was respectively 2.4 and 2 folds higher than that in the control group (p <0.01). Besides, the volume density of the lumen was significantly higher in the single layer suturing when compared to the double layer suturing group (p <0.01). However, no significant difference was observed among the study groups regarding the volume density of the collagen and vessels in the incised site of the penis which implied that the fraction of the urethra and surrounding corpus spongiosum was occupied by collagen and vessels. Conclusions Urethral plate repair by the single layer suturing method could be accompanied by higher epithelialization and wider lumen in the rabbit model of hypospadias. PMID:28127462

  9. Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model

    PubMed Central

    Izuhara, Masayasu; Kuwabara, Yasuhide; Saito, Naritatsu; Yamamoto, Erika; Hakuno, Daihiko; Nakashima, Yasuhiro; Horie, Takahiro; Baba, Osamu; Nishiga, Masataka; Nakao, Tetsushi; Nishino, Tomohiro; Nakazeki, Fumiko; Ide, Yuya; Kimura, Masahiro; Kimura, Takeshi; Ono, Koh

    2017-01-01

    Background Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation. Methods and results We designed and constructed a 27-nt double strand RNA (dsRNA) conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly (DL-lactide-co-glycolide) nanoparticles (NPs). miR-126-dsRNA-containing NPs (miR-126 NPs) significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells (HUVECs), and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis. Conclusions miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty. PMID:28253326

  10. The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model

    PubMed Central

    BRENNER, M.; BENAVIDES, S.; MAHON, S. B.; LEE, J.; YOON, D.; MUKAI, D.; VISEROI, M.; CHAN, A.; JIANG, J.; NARULA, N.; AZER, S. M.; ALEXANDER, C.; BOSS, G. R.

    2014-01-01

    Background and purpose Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. Methods New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1—saline (placebo group, N = 9); Group 2—IV hydroxocobalamin (N = 7); Group 3—IV aquohydroxocobinamide (N = 6); Group 4—IV sulfitocobinamide (N = 6); Group 5—intramuscular (IM) sulfitocobinamide (N = 6); and Group 6—IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Results Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. Conclusions Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. PMID:24716792

  11. Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

    PubMed Central

    2010-01-01

    Background Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the Pistacia vera nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis. Methods and results Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months. Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration. Conclusions During short-term administration concomitantly with atherogenic diet, both P. vera extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that P. vera dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management. PMID:20633299

  12. Anti-adhesive effect of poloxamer-based thermo-sensitive sol-gel in rabbit laminectomy model.

    PubMed

    Shin, Sung Joon; Lee, Jae Hyup; So, Jungwon; Min, Kyungdan

    2016-11-01

    Poloxamer-based thermo-sensitive sol-gel has been developed to reduce the incidence of postoperative scar formation at the laminectomy site. The purpose of this study was to evaluate the anti-adhesive effect of poloxamer based thermo-sensitive sol-gel compared to hyaluronate based solution after laminectomy, using a rabbit model. A thermo-sensitive anti-adhesive with a property of sol-gel transition was manufactured by a physical mixture of Poloxamer188/407, Chitosan and Gelatin. The viscosity in different temperatures was assessed. 72 adult New Zealand rabbits underwent lumbar laminectomy and were randomly divided into experimental (treated with the newly developed agent), positive (treated with hyaluronate based solution), and negative control groups. Each group was subdivided into 1 and 4-week subgroups. Gross and histological evaluations were performed to assess the extent of epidural adhesion. The experimental group showed significantly higher viscosity compared to the positive control group and showed a significant increase of viscosity as the temperature increased. Gross evaluation showed no statistically significant differences between the 1- and 4-week subgroups. However, histologic evaluation showed significant differences both in 1- and 4-week subgroups. Although the 4-week histologic results of the experimental and the positive control subgroups showed no significant difference, both subgroups revealed higher value compared to the negative control subgroup with regard to the ratio of adhesion less than 50 %. The new poloxamer based thermo-sensitive agent showed superior efficacy over the hyaluronate based agent at 1 week postoperatively. At 4 weeks postoperatively, there were no statistically significant differences between the two agents, although both showed efficacy over the sham group.

  13. Neonatal Neurobehavior and Diffusion MRI Changes in Brain Reorganization Due to Intrauterine Growth Restriction in a Rabbit Model

    PubMed Central

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

    2012-01-01

    Background Intrauterine growth restriction (IUGR) affects 5–10% of all newborns and is associated with a high risk of abnormal neurodevelopment. The timing and patterns of brain reorganization underlying IUGR are poorly documented. We developed a rabbit model of IUGR allowing neonatal neurobehavioral assessment and high resolution brain diffusion magnetic resonance imaging (MRI). The aim of the study was to describe the pattern and functional correlates of fetal brain reorganization induced by IUGR. Methodology/Principal Findings IUGR was induced in 10 New Zealand fetal rabbits by ligation of 40–50% of uteroplacental vessels in one horn at 25 days of gestation. Ten contralateral horn fetuses were used as controls. Cesarean section was performed at 30 days (term 31 days). At postnatal day +1, neonates were assessed by validated neurobehavioral tests including evaluation of tone, spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and coordination of suck and swallow. Subsequently, brains were collected and fixed and MRI was performed using a high resolution acquisition scheme. Global and regional (manual delineation and voxel based analysis) diffusion tensor imaging parameters were analyzed. IUGR was associated with significantly poorer neurobehavioral performance in most domains. Voxel based analysis revealed fractional anisotropy (FA) differences in multiple brain regions of gray and white matter, including frontal, insular, occipital and temporal cortex, hippocampus, putamen, thalamus, claustrum, medial septal nucleus, anterior commissure, internal capsule, fimbria of hippocampus, medial lemniscus and olfactory tract. Regional FA changes were correlated with poorer outcome in neurobehavioral tests. Conclusions IUGR is associated with a complex pattern of brain reorganization already at birth, which may open opportunities for early intervention. Diffusion MRI can offer suitable imaging biomarkers to characterize and monitor

  14. Combining subject-specific and low-order modeling techniques to study fluid-structure interaction of rabbit phonation

    NASA Astrophysics Data System (ADS)

    Chang, Siyuan; Luo, Haoxiang; Novaleski, Carolyn; Rousseau, Bernard

    2014-11-01

    A subject-specific computational model has been developed to simulate flow-induced vocal fold vibration for evoked rabbit phonation. A freshly excised larynx was scanned using micro magnetic resonance imaging. Images were segmented to identify the vocal fold tissue and lumen surface. The 3D fluid-structure interaction (FSI) model was then constructed with experimentally measured flow parameters as input. The tissue deformation is assumed to be finite, and a previously developed FSI solver is used to simulate the coupled flow and nonlinear tissue mechanics. In addition, a one-dimensional flow model based on heuristic estimate of the flow separation point is used as an efficient tool to guide the full 3D simulation. This low-order model is motivated by presence of uncertainties in the tissue properties and boundary conditions, and it has proven to be very useful in our study. Similarities and differences in the vibration characteristics of the vocal fold predicted by these two models will be discussed.

  15. RABBIT POX

    PubMed Central

    Rosahn, Paul D.; Hu, Ch'uan-K'uei

    1935-01-01

    Observations on an epidemic of rabbit pox occurring in an isolated animal room during the winter of 1933–34 are reported. The clinical manifestations, consisting of a generalized papular eruption involving the skin and mucous membranes, together with blepharitis, ophthalmia, nasal discharge and lymphadenopathy were essentially similar to those noted in a pox epidemic of the previous year. This was true in general also of the pathological findings except that vacuolization, local necrosis and vesicle formation were seen in the epidermis, while in the previous year the microscopic pathology in the skin was confined to the corium. Evidence was presented indicating that the infection can be transmitted through the medium of a personal carrier, and that transmission in this manner can occur during the incubation period or before a definite diagnosis is possible. The findings also demonstrated that the etiological agents responsible for the disease reported here and that of the previous year were immunologically related, and that the immunity in recovered animals effectively persisted during the entire period for which data are available, 9 to 12 months. It appeared also that young animals suckling an immune doe were more refractory to the development of the lesions of rabbit pox than were the young of susceptible does. PMID:19870418

  16. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Rao, Pramod P.; Pascale, Florentina; Seck, Atman; Auperin, Anne; Drouard-Troalen, Laurence; Deschamps, Frederic; Teriitheau, Christophe; Paci, Angelo; Denys, Alban; Bize, Pierre; Baere, Thierry de

    2012-12-15

    Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

  17. Massage Timing Affects Postexercise Muscle Recovery and Inflammation in a Rabbit Model

    PubMed Central

    Haas, Caroline; Butterfield, Timothy A.; Abshire, Sarah; Zhao, Yi; Zhang, Xiaoli; Jarjoura, David; Best, Thomas M

    2013-01-01

    Purpose This study compared the effect of immediate versus delayed massage-like compressive loading (MLL) on peak isometric torque recovery and inflammatory cell infiltration following eccentric exercise (EEX). Methods Eighteen skeletally mature New Zealand White rabbits were instrumented with peroneal nerve cuffs for stimulation of hindlimb tibialis anterior muscles. Following a bout of EEX, rabbits were randomly assigned to a MLL protocol (0.5Hz, 10N, 15min) started immediately post-EEX, 48 hours post-EXX, or no-MLL control and performed for four consecutive days. A torque-angle (T-Θ) relationship was obtained for 21 joint angles pre and post-EEX and post four consecutive days of MLL or no-MLL. Muscle wet weights and immunohistochemical sections were obtained following final treatments. Results EEX produced an average 51% (±13%) decrease in peak isometric torque output. Greatest peak torque recovery occurred with immediate application of MLL. There were differences in torque recovery between immediate and delayed MLL (p=0.0012), immediate MLL and control (p<0.0001), and delayed MLL and control (p=0.025). Immunohistochemical analysis showed 39.3% and 366.0% differences in the number of RPN3/57 and CD11b positive cells between immediate (p=0.71) and delayed MLL (p=0.12). Area under the T-Θ curve showed a difference for immediate (p<0.0001) and delayed (p=0.0051) MLL as compared to control. Exercise produced an average 10°± 0.2 rightward shift from pre exercise peak isometric torque angle. Control, immediate MLL and delayed MLL produced an average leftward angular shift from the post exercise angle (p=0.28, p=0.03, and p=0.47, respectively). Conclusion Post-EEX, immediate MLL was more beneficial than delayed MLL in restoring muscle function and modulating inflammatory cell infiltration. These findings invite similar human studies in order to make definitive conclusions on optimal timing of massage-based therapies. PMID:23274593

  18. AMECM/DCB scaffold prompts successful total meniscus reconstruction in a rabbit total meniscectomy model.

    PubMed

    Yuan, Zhiguo; Liu, Shuyun; Hao, Chunxiang; Guo, Weimin; Gao, Shuang; Wang, Mingjie; Chen, Mingxue; Sun, Zhen; Xu, Yichi; Wang, Yu; Peng, Jiang; Yuan, Mei; Guo, Quan-Yi

    2016-12-01

    Tissue-engineered meniscus regeneration is a very promising treatment strategy for meniscus lesions. However, generating the scaffold presents a huge challenge for meniscus engineering as this has to meet particular biomechanical and biocompatibility requirements. In this study, we utilized acellular meniscus extracellular matrix (AMECM) and demineralized cancellous bone (DCB) to construct three different types of three-dimensional porous meniscus scaffold: AMECM, DCB, and AMECM/DCB, respectively. We tested the scaffolds' physicochemical characteristics and observed their interactions with meniscus fibrochondrocytes to evaluate their cytocompatibility. We implanted the three different types of scaffold into the medial knee menisci of New Zealand rabbits that had undergone total meniscectomy; negative control rabbits received no implants. The reconstructed menisci and corresponding femoral condyle and tibial plateau cartilage were all evaluated at 3 and 6 months (n = 8). The in vitro study demonstrated that the AMECM/DCB scaffold had the most suitable biomechanical properties, as this produced the greatest compressive and tensile strength scores. The AMECM/DCB and AMECM scaffolds facilitated fibrochondrocyte proliferation and the secretion of collagen and glycosaminoglycans (GAGs) more effectively than did the DCB scaffold. The in vivo experiments demonstrated that both the AMECM/DCB and DCB groups had generated neomeniscus at both 3 and 6 months post-implantation, but there was no obvious meniscus regeneration in the AMECM or control groups, so the neomeniscus analysis could not perform on AMECM and control group. At both 3 and 6 months, histological scores were better for regenerated menisci in the AMECM/DCB than in the DCB group, and significantly better for articular cartilage in the AMECM/DCB group compared with the other three groups. Knee MRI scores (Whole-Organ Magnetic Resonance Imaging Scores (WORMS)) were better in the AMECM/DCB group than in the

  19. Decreased Temporomandibular Joint Range of Motion in a Model of Early Osteoarthritis in the Rabbit

    PubMed Central

    Henderson, Sarah E.; Tudares, Mauro A.; Tashman, Scott; Almarza, Alejandro J.

    2015-01-01

    Purpose Analysis of mandibular biomechanics could help with understanding the mechanisms of temporomandibular joint (TMJ) disorders (TMJDs), such as osteoarthritis (TMJ-OA), by investigating the effects of injury or disease on TMJ movement. The objective of the present study was to determine the functional kinematic implications of mild TMJ-OA degeneration caused by altered occlusion from unilateral splints in the rabbit. Materials and Methods Altered occlusion of the TMJ was mechanically induced in rabbits by way of a unilateral molar dental splint (n = 3). TMJ motion was assessed using 3-dimensional (3D) skeletal kinematics twice, once before and once after 6 weeks of splint placement with the splints removed, after allowing 3 days of recovery. The relative motion of the condyle to the fossa and the distance between the incisors were tracked. Results An overall decrease in the range of joint movement was observed at the incisors and in the joint space between the condyle and fossa. The incisor movement decreased from 7.0 ± 0.5 mm to 6.2 ± 0.5 mm right to left, from 5.5 ± 2.2 mm to 4.6 ± 0.8 mm anterior to posterior, and from 13.3 ± 1.8 mm to 11.6 ± 1.4 mm superior to inferior (P < .05). The total magnitude of the maximum distance between the points on the condyle and fossa decreased from 3.6 ± 0.8 mm to 3.1 ± 0.6 mm for the working condyle and 2.8 ± 0.4 mm to 2.5 ± 0.4 mm for the balancing condyle (P < .05). The largest decreases were seen in the anteroposterior direction for both condyles. Conclusion Determining the changes in condylar movement might lead to a better understanding of the early predictors in the development of TMJ-OA and determining when the symptoms become a chronic, irreversible problem. PMID:25889371

  20. Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model

    SciTech Connect

    Gupta, Sanjay Wright, Kenneth C.; Ensor, Joe; Van Pelt, Carolyn S.; Dixon, Katherine A.; Kundra, Vikas

    2011-10-15

    Objectives: The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods: Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results: The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions: Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.

  1. Hydroxyapatite coating on PEEK implants: Biomechanical and histological study in a rabbit model.

    PubMed

    Durham, John W; Montelongo, Sergio A; Ong, Joo L; Guda, Teja; Allen, Matthew J; Rabiei, Afsaneh

    2016-11-01

    A bioactive two-layer coating consisting of hydroxyapatite (HA) and yttria-stabilized zirconia (YSZ) was investigated on cylindrical polyetheretherketone (PEEK) implants using ion beam assisted deposition (IBAD). Post-deposition heat treatments via variable frequency microwave annealing with and without subsequent autoclaving were used to crystallize the as-deposited amorphous HA layer. Microstructural analysis, performed by TEM and EDS, showed that these methods were capable of crystallizing HA coating on PEEK. The in vivo response to cylindrical PEEK samples with and without coating was studied by implanting uncoated PEEK and coated PEEK implants in the lateral femoral condyle of 18 rabbits. Animals were studied in two groups of 9 for observation at 6 or 18weeks post surgery. Micro-CT analysis, histology, and mechanical pull-out tests were performed to determine the effect of the coating on osseointegration. The heat-treated HA/YSZ coatings showed improved implant fixation as well as higher bone regeneration and bone-implant contact area compared to uncoated PEEK. The study offers a novel method to coat PEEK implants with improved osseointegration.

  2. Stress shielding of patellar tendon: effect on small-diameter collagen fibrils in a rabbit model.

    PubMed

    Majima, Tokifumi; Yasuda, Kazunori; Tsuchida, Takamasa; Tanaka, Kunio; Miyakawa, Kiyoshi; Minami, Akio; Hayashi, Kozaburo

    2003-01-01

    The purpose of this study was to assess the effects of stress shielding on the microstructure and ultrastructure of the patellar tendon using 40 mature female Japanese white rabbits. The patellar tendon was completely released from stress by drawing the patella toward the tibial tubercle with a stainless steel wire installed between them. Microstructurally, stress shielding for 3 and 6 weeks increased the number of cells approximately fivefold, to that of the control tendon. Collagen bundles were less well oriented in the stress-shielded tendon than in the control. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm increased in the stress-shielded tendon. The median collagen fibril diameter in 6-week stress-shielded tendon was significantly smaller ( P < 0.05) than in the control tendon (58.8% of control). The ratio of the total area of collagen fibrils to the whole visualized area in the stress-shielded patellar tendon was significantly smaller at 3 and 6 weeks than that in the control. This study demonstrated that complete stress shielding significantly affects the microstructure and ultrastructure of the patellar tendon

  3. Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

    PubMed Central

    Kim, Sungtae; Kim, Se Won; Lee, Jong Ho

    2016-01-01

    Absorbable extracellular matrix (ECM) membrane has recently been used as a barrier membrane (BM) in guided tissue regeneration (GTR) and guided bone regeneration (GBR). Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP) showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18–0.35 mm) but with excellent mechanical properties. Tensile strength of APP was 14.15 ± 2.24 MPa. In in vivo experiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months. PMID:27047963

  4. Semisolid formulations containing cetirizine: human skin permeation and topical antihistaminic evaluation in a rabbit model.

    PubMed

    Ciurlizza, Claudia; Fernández, Francisco; Calpena, Ana Cristina; Lázaro, Raquel; Parra, Alexander; Clares, Beatriz

    2014-10-01

    Cetirizine dihydrochloride (CTZ) is a second-generation histamine H1 antagonist, effective for the treatment of a wide range of allergic diseases. It has been utilized for managing the symptoms of chronic urticaria and atopic skin conditions. Thus, two novel semisolid formulations, nanoemulsion (NE) and hydrogel (HG) were developed to study their potential utility as vehicles including cetirizine (CTZ) and evaluate the potential use as topical H1-antihistamines agents. The physicochemical and stability properties of both vehicles were tested. Drug release kinetics and human skin permeation studies were performed using Franz cells. The antihistaminic activity was assayed in New Zealand rabbits and compared with two commercial first generation antihistamines. Both formulations were stable and provided a sustained drug release. Amounts of CTZ remaining in the skin were higher for HG, showing the maximum biological effect at 30 min, similar to topical first generation H1-antihistamines commercially available. These results suggest that CTZ-HG could be a promising system for the treatment of topical allergy bringing rapid antihistaminic relief.

  5. Development of an Optimal Diaphragmatic Hernia Rabbit Model for Pediatric Thoracoscopic Training

    PubMed Central

    Pérez-Merino, Eva M.; Usón-Casaús, Jesús M.; Zaragoza-Bayle, Concepción; Rivera-Barreno, Ramón; Rodríguez-Alarcón, Carlos A.; Palme, Rupert; Sánchez-Margallo, Francisco M.

    2014-01-01

    Our objectives were to standarize the procedure needed to reproduce a similar surgical scene which a pediatric surgeon would face on repairing a Bochdalek hernia in newborns and to define the optimal time period for hernia development that achieve a realistic surgical scenario with minimimal animal suffering. Twenty New Zealand white rabbits weighing 3–3.5 kg were divided into four groups depending on the time frame since hernia creation to thoracoscopic repair: 48 h, 72 h, 96 h and 30 days. Bochdalek trigono was identified and procedures for hernia creation and thoracoscopic repair were standarized. Blood was collected for hematology (red blood cells, white blood cells, platelets, hemoglobin and hematocrit), biochemistry (blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase) and gas analysis (arterial blood pH, partial pressure of oxygen, partial pressure of carbón dioxide, oxygen saturation and bicarbonate) at baseline and before the surgial repairment. Glucocorticoid metabolites concentration in faeces was measured. Thoracoscopy video recordings were evaluated by six pediatric surgeons and rated from 0 to 10 according to similarities with congenital diaphragmatic hernia in newborn and with its thoracoscopic approach. Statistical methods included the analysis of variance, and comparisons between groups were followed by a post-hoc Tukey’s test. Fourty -eight h showed to be the optimal time frame to obtain a diaphragmatic hernia similar to newborn scenario from a surgical point of view with minimal stress for the animals. PMID:24521868

  6. Repair of the Orbital Wall Fractures in Rabbit Animal Model Using Nanostructured Hydroxyapatite-Based Implant

    PubMed Central

    Gradinaru, Sinziana; Popescu, Laura Madalina; Piticescu, Roxana Mioara; Zurac, Sabina; Ciuluvica, Radu; Burlacu, Alexandrina; Tutuianu, Raluca; Valsan, Sorina-Nicoleta; Motoc, Adrian Mihail; Voinea, Liliana Mary

    2016-01-01

    Cellular uptake and cytotoxicity of nanostructured hydroxyapatite (nanoHAp) are dependent on its physical parameters. Therefore, an understanding of both surface chemistry and morphology of nanoHAp is needed in order to be able to anticipate its in vivo behavior. The aim of this paper is to characterize an engineered nanoHAp in terms of physico-chemical properties, biocompatibility, and its capability to reconstitute the orbital wall fractures in rabbits. NanoHAp was synthesized using a high pressure hydrothermal method and characterized by physico-chemical, structural, morphological, and optical techniques. X-ray diffraction revealed HAp crystallites of 21 nm, while Scanning Electron Microscopy (SEM) images showed spherical shapes of HAp powder. Mean particle size of HAp measured by DLS technique was 146.3 nm. Biocompatibility was estimated by the effect of HAp powder on the adhesion and proliferation of mesenchymal stem cells (MSC) in culture. The results showed that cell proliferation on powder-coated slides was between 73.4% and 98.3% of control cells (cells grown in normal culture conditions). Computed tomography analysis of the preformed nanoHAp implanted in orbital wall fractures, performed at one and two months postoperative, demonstrated the integration of the implants in the bones. In conclusion, our engineered nanoHAp is stable, biocompatible, and may be safely considered for reconstruction of orbital wall fractures.

  7. In vivo tissue response and durability of five novel synthetic polymers in a rabbit model.

    PubMed

    Sahin, E; Cingi, C; Eskiizmir, G; Altintoprak, N; Calli, A; Calli, C; Yilgör, I; Yilgör, E

    2016-04-01

    Alloplastic materials are frequently used in facial plastic surgeries such as rhinoplasty and nasal reconstruction. Unfortunately, the ideal alloplastic material has not been found. This experimental study evaluates the tissue response and durability of five novel polymers developed as an alloplastic material. In this experimental study involving a tertiary university hospital, six subcuticular pockets were formed at the back of 10 rabbits for the implantation of each polymer and sham group. Each pocket was excised with its adjacent tissue after three months, and collected for histopathological examination. Semi-quantitative examination including neovascularisation, inflammation, fibrosis, abscess formation, multinucleated foreign body giant cells was performed, and integrity of polymer was evaluated. A statistical comparison was performed. No statically significant difference was detected in neovascularisation, inflammation, fibrosis, abscess formation and multinucleated foreign body giant cells when a paired comparison between sham and polymer II, III and IV groups was performed individually. Nevertheless, the degree of fibrosis was less than sham group in polymer I (p = .027) and V (p = .018), although the other variables were almost similar. The integrity of polymers III (9 intact, 1 fragmented) and IV (8 intact, 2 absent) was better than the other polymers. These novel synthetic polymers could be considered as good candidates for clinical applicability. All polymers provided satisfactory results in terms of tissue response; however, fibrovascular integration was higher in polymers II, III and IV. In addition, the durability of polymer III and IV was better than the others.

  8. The Effect of Sodium Hyaluronate on Ligamentation and Biomechanical Property of Tendon in Repair of Achilles Tendon Defect with Polyethylene Terephthalate Artificial Ligament: A Rabbit Tendon Repair Model

    PubMed Central

    Li, Shengkun; Jiang, Jia; Chen, Shiyi

    2016-01-01

    The Achilles tendon is the most common ruptured tendon of human body. Reconstruction with polyethylene terephthalate (PET) artificial ligament is recommended in some serious cases. Sodium hyaluronate (HA) is beneficial for the healing of tendon injuries. We aimed to determine the effect of sodium hyaluronate in repair of Achilles tendon defect with PET artificial ligament in an animal tendon repair model. Sixteen New Zealand White rabbits were divided into two groups. Eight rabbits repaired with PET were assigned to PET group; the other eight rabbits repaired with PET along with injection of HE were assigned to HA-PET group. All rabbits were sacrificed at 4 and 8 weeks postoperatively for biomechanical and histological examination. The HA-PET group revealed higher biomechanical property compared with the PET group. Histologically, more collagen tissues grew into the HA-PET group compared with PET group. In conclusion, application of sodium hyaluronate can improve the healing of Achilles tendon reconstruction with polyethylene terephthalate artificial ligament. PMID:28105436

  9. In vivo evaluation of a biodegradable donut-shaped minitablet for prolonged posterior segment drug delivery in the rabbit eye model.

    PubMed

    Choonara, Yahya E; Pillay, Viness; Danckwerts, Michael Paul; Carmichael, Trevor R; Meyer, Leith C R; Du Toit, Lisa C; Naylor, Simon; Wanblad, Carla

    2011-05-01

    This study focused on the in vivo evaluation of a biodegradable ganciclovir-loaded donut-shaped minitablet (DSMT) for controlled drug delivery in the New Zealand white albino rabbit eye model. Specialized tablet tooling was used to manufacture a poly(lactic-co-glycolic acid) DSMT device that was implanted into 18 rabbits through the pars plana/peripheral retina of the right eyes of each rabbit. The left eyes were used as controls. Possible adverse effects on ocular tissues were assessed by histomorphology, slit-lamp biomicroscopy, intraocular pressure (IOP) measurements, and indirect ophthalmoscopy. The ex vivo microenvironmental vitreous pH was also monitored. Rabbits were euthanized at predetermined intervals and the residual devices, vitreous humor, and ocular tissue were retrieved and stored appropriately until further analysis. The DSMT was well tolerated up to 72 days and was still visible in the superotemporal quadrant of the eye. The mean IOP range (6-8 mmHg; N = 18) and changes in vitreous pH (7.25 ± 0.01; N = 3) correlated with baseline measurements. The DSMT displayed constant ganciclovir release at a rate of 2.02 μ g/h maintained within the 50% effective dose for human cytomegalovirus retinitis (N = 3). The design simplicity and application of the biodegradable DSMT device may provide a superior alternative for prolonged rate-controlled intraocular drug delivery.

  10. Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model

    PubMed Central

    Sugaya, Hisashi; Aoto, Katsuya; Uemura, Kenta; Tanaka, Kenta; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

    2017-01-01

    No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy. PMID:28386485

  11. Ceftaroline-Fosamil Efficacy against Methicillin-Resistant Staphylococcus aureus in a Rabbit Prosthetic Joint Infection Model

    PubMed Central

    Gatin, Laure; Saleh-Mghir, Azzam; Tasse, Jason; Ghout, Idir; Laurent, Frédéric

    2014-01-01

    Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstrates in vitro bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 107 MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the in vivo mean log10 CFU/g of CPT-treated (3.0 ± 0.9, n = 12) and VAN-treated (3.5 ± 1.1, n = 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1, n = 14) (P < 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs. PMID:25136014

  12. Ceftaroline-Fosamil efficacy against methicillin-resistant Staphylococcus aureus in a rabbit prosthetic joint infection model.

    PubMed

    Gatin, Laure; Saleh-Mghir, Azzam; Tasse, Jason; Ghout, Idir; Laurent, Frédéric; Crémieux, Anne-Claude

    2014-11-01

    Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstrates in vitro bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 10(7) MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the in vivo mean log10 CFU/g of CPT-treated (3.0 ± 0.9, n = 12) and VAN-treated (3.5 ± 1.1, n = 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1, n = 14) (P < 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs.

  13. Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration

    PubMed Central

    SHI, LIJUN; TENG, HONGLIN; ZHU, MINYU; LI, CHI; HUANG, KELUN; CHEN, BI; DAI, YUSEN; WANG, JING

    2015-01-01

    Apoptosis plays a key role in the pathogenesis of internal disc disruption (IDD); therefore, the inhibition of apoptosis may offer a novel approach for treating IDD diseases. The aim of the present study was to investigate the effects and the underlying mechanisms of paeoniflorin through the detection of relevant indicators in a rabbit model of IDD. In total, 144 rabbits were used in the study and divided into four groups (n=36 per group). Rabbits successfully modeled with IDD received an intragastric injection of 120 mg/kg·day paeoniflorin (high-dose group), 30 mg/kg·day paeoniflorin (low-dose group) or saline (model saline group), while rabbits without IDD were used as a normal control group. The apoptosis rate of disc nucleus pulposus cells was detected using flow cytometry. In addition, the expression levels of Bcl-2, Bax and caspase-9 in the disc tissues were detected using immunohistochemistry and western blot analysis prior to and following the treatment. The results indicated that the expression levels of Bax in the low- and high-dose paeoniflorin groups were significantly reduced, while the Bcl-2 expression levels were significantly increased when compared with the model saline group (P<0.01). In addition, the expression levels of cleaved caspase-3 and cleaved caspase-9 were reduced in the low- and high-dose paeoniflorin groups, as compared with the model saline group (P<0.05). Furthermore, the average apoptotic index of the high- and low-dose paeoniflorin groups was decreased when compared with the model saline group (P<0.05). In conclusion, paeoniflorin was demonstrated to inhibit the apoptosis of nucleus pulposus cells and the activation of caspase-3 and caspase-9 through the regulation of Bcl-2 family protein expression. These results provide an experimental basis for the future treatment of IDD with paeoniflorin. PMID:26170945

  14. Confocal microscopic analysis of a rabbit eye model of high incidence recurrent herpes stromal keratitis (HSK)

    PubMed Central

    Jester, James V.; Morishige, Naoyuki; BenMohamed, Lbachir; Brown, Donald J.; Osorio, Nelson; Hsiang, Chinhui; Perng, Guey Chuen; Jones, Clinton; Wechsler, Steven L.

    2015-01-01

    Purpose Using CJLAT, a chimeric herpes simplex virus (HSV-1) that produces a high incidence of herpes stromal keratitis (HSK) in latently infected rabbits, we characterized, by in vivo confocal microscopy (CM), the cellular events that precede development of HSK. Methods Thirty days post infection, in vivo CM was performed daily for 10 days and then weekly for up to 80 days post infection. Results We detected three types of subclinical corneal lesions prior to clinically apparent HSK: i)Small epithelial erosions; ii)Regenerating epithelium overlying small, cell infiltrates within the basal epithelial cell layer; and iii)Dendritic-like cells within the basal epithelial layer overlying stromal foci containing infiltrating cells. Sequential in vivo CM observations suggested that subclinical foci resolved over time, but were larger and more abundant with CJLAT than wild type HSV-1 McKrae. Active HSK was observed only with CJLAT and was initially associated with a large epithelial lesion overlying stromal immune cell infiltrates. Conclusions These results suggest that replication in the cornea of reactivated virus from trigeminal ganglia produces epithelial lesions which recruit immune cell infiltrates into the basal epithelial layer and anterior stroma. The virus is usually cleared rapidly eliminating viral antigens (Ags) prior to the arrival of the immune cells, which disperse. However, if the virus is not cleared rapidly, or if an additional reactivation results in an additional round of virus at the same site before the immune cells disperse, then the immune cells are stimulated and may induce an immunopathological response leading to the development of HSK. PMID:26555580

  15. Reconstruction of auto-tissue-engineered lamellar cornea by dynamic culture for transplantation: a rabbit model.

    PubMed

    Wu, Zheng; Zhou, Qiang; Duan, Haoyun; Wang, Xiaoran; Xiao, Jianhui; Duan, Hucheng; Li, Naiyang; Li, Chaoyang; Wan, Pengxia; Liu, Ying; Song, Yiyue; Zhou, Chenjing; Huang, Zheqian; Wang, Zhichong

    2014-01-01

    To construct an auto-tissue-engineered lamellar cornea (ATELC) for transplantation, based on acellular porcine corneal stroma and autologous corneal limbal explants, a dynamic culture process, which composed of a submersion culture, a perfusion culture and a dynamic air-liquid interface culture, was performed using appropriate parameters. The results showed that the ATELC-Dynamic possessed histological structure and DNA content that were similar to native lamellar cornea (NLC, p>0.05). Compared to NLC, the protein contents of zonula occludens-1, desmocollin-2 and integrin β4 in ATELC-Dynamic reached 93%, 89% and 73%, respectively. The basal cells of ATELC-Dynamic showed a better differentiation phenotype (K3-, P63+, ABCG2+) compared with that of ATELC in static air-lift culture (ATELC-Static, K3+, P63-, ABCG2-). Accordingly, the cell-cloning efficiency of ATELC-Dynamic (9.72±3.5%) was significantly higher than that of ATELC-Static (2.13±1.46%, p<0.05). The levels of trans-epithelial electrical resistance, light transmittance and areal modulus variation in ATELC-Dynamic all reached those of NLC (p>0.05). Rabbit lamellar keratoplasty showed that the barrier function of ATELC-Dynamic was intact, and there were no signs of epithelial shedding or neovascularization. Furthermore, the ATELC-Dynamic group had similar optical properties and wound healing processes compared with the NLC group. Thus, the sequential dynamic culture process that was designed according to corneal physiological characteristics could successfully reconstruct an auto-lamellar cornea with favorable morphological characteristics and satisfactory physiological function.

  16. Transarterial Sorafenib Chemoembolization: Preliminary Study of Technical Feasibility in a Rabbit Model

    PubMed Central

    Gaba, Ron C.; Yap, Felix Y.; Martinez, Elizabeth M.; Li, Yongchao; Guzman, Grace; Parvinian, Ahmad; van Breemen, Richard B.; Kumar, Nishant

    2014-01-01

    Purpose To test the feasibility of targeted intra-arterial administration of the tyrosine kinase inhibitor chemotherapeutic agent sorafenib to inhibit embolotherapy-induced tumor angiogenesis and reduce systemic drug side effects. Materials and Methods The left hepatic lobes of five New Zealand White rabbits (mean weight 2.7 ± 0.2 kg) were treated with chemoembolization using sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Post-procedure noncontrast computed tomography (CT) was used to evaluate intrahepatic chemotherapy mixture distribution. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure sorafenib concentration in the treated liver tissue. Histopathological assessment of treated left lobes was performed to identify any immediate toxic effects of the sorafenib solution. Results Lobar sorafenib chemoembolization was successfully performed in all cases via the left hepatic artery. Sorafenib and ethiodized oil (mean 6.4 mg ± 3.8 and 0.95 mL ± 0.7 mL, respectively) were injected, and CT confirmed targeted left hepatic lobe sorafenib emulsion delivery in all cases. Corresponding LC-MS/MS analysis yielded a mean sorafenib concentration of 94.2 μg/mL ± 48.3 in treated left lobe samples (n = 5), significantly greater than typical therapeutic drug levels (2–10 μg/mL) achieved with oral sorafenib systemic therapy. Histopathological assessment showed only mild or moderate non-specific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis. Conclusions Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than that reported for systemic sorafenib therapy, without immediate histopathological tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors. PMID:23510657

  17. Transarterial Chemoembolization Using Cisplatin Powder in a Rabbit Model of Liver Cancer

    SciTech Connect

    Morimoto, Kengo Sakaguchi, Hiroshi; Tanaka, Toshihiro; Yamamoto, Kiyosei; Anai, Hiroshi; Hayashi, Takayuki; Satake, Mitsuo; Kichikawa, Kimihiko

    2008-09-15

    The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 {mu}g/ml for the cisplatin-HAI group, 1.23 {mu}g/ml for the cisplatin-GS-TACE group, and 12.65 {mu}g/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 {mu}g/ml for the cisplatin-HAI group, 1.13 {mu}g/ml for the cisplatin-GS-TACE group, and 1.09 {mu}g/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

  18. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

    PubMed Central

    Boakye, Lorraine A; Ross, Keir A; Pinski, John M; Smyth, Niall A; Haleem, Amgad M; Hannon, Charles P; Fortier, Lisa A; Kennedy, John G

    2015-01-01

    AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-β1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-β1 was then assessed. RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10-4, 3.1 × 10-4 and 7.3 × 10-3 for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10-6) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo. PMID:26716092

  19. Lavage with Allicin in Combination with Vancomycin Inhibits Biofilm Formation by Staphylococcus epidermidis in a Rabbit Model of Prosthetic Joint Infection

    PubMed Central

    Zhai, Haohan; Pan, Jianchao; Pang, En; Bai, Bo

    2014-01-01

    Background and Aim The present anti-infection strategy for prosthetic joint infections (PJI) includes the use of antibiotics and surgical treatments, but the bacterial eradication rates are still low. One of the major challenges is the formation of biofilm causing poor bacterial eradication. Recently it has been reported that allicin (diallyl thiosulphinate), an antibacterial principle of garlic, can inhibit bacteria adherence and prevent biofilm formation in vitro. However, whether allicin could inhibit biofilm formation in vivo is unknown. The aim of this study was to investigate the effects of allicin on biofilm formation, and whether allicin could potentiate the bactericidal effect of vancomycin in a rabbit PJI model. Methods A sterile stainless-steel screw with a sterile ultra-high molecular weight polyethylene washer was inserted into the lateral femoral condyle of the right hind knee joint of rabbit, and 1 mL inoculum containing 104 colony-forming units of Staphylococcus epidermidis was inoculated into the knee joint (n = 32). Fourteen days later, rabbits randomly received one of the following 4 treatments using continuous lavages: normal saline, vancomycin (20 mcg/mL), allicin (4 mg/L), or allicin (4 mg/L) plus vancomycin (20 mcg/mL). Three days later, the washer surface biofilm formation was examined by scanning electron microscopy (SEM). The bacterial counts within the biofilm of implanted screws were determined by bacterial culture. Results The lowest number of viable bacterial counts of Staphylococcus epidermidis recovered from the biofilm was in the rabbits treated with allicin plus vancomycin (P<0.01 vs. all other groups). The biofilm formation was significantly reduced or undetectable by SEM in rabbits receiving allicin or allicin plus vancomycin. Conclusion Intra-articular allicincan inhibit biofilm formation and enhance the bactericidal effect of vancomycin on implant surface in vivo. Allicin in combination with vancomycin may be a useful anti

  20. Permeability characteristics of novel mydriatic agents using an in vitro cell culture model that utilizes SIRC rabbit corneal cells.

    PubMed

    Goskonda, V R; Khan, M A; Hutak, C M; Reddy, I K

    1999-02-01

    The purpose of this study was to evaluate the permeability characteristics of a previously reported in vitro corneal model that utilizes SIRC rabbbit corneal cells and to investigate the permeability of three novel esters of phenylephrone chemical delivery systems (CDS) under different pH conditions using this in vitro model. The SIRC rabbit corneal cell line was grown on transwell polycarbonate membranes, and the barrier properties were assessed by measuring transepithelial electrical resistance (TEER) using a voltohmmeter. The permeabilities of esters of phenylephrone CDS across the SIRC cell layers were measured over a pH range 4.0-7. 4. The esters tested include phenylacetyl (1), isovaleryl (2), and pivalyl (3). The SIRC rabbit corneal cell line, when grown on permeable filters, formed tight monolayers of high electrical resistance with TEER values increasing from 71.6 +/- 20.8 Omega.cm2 at day 3 in culture to 2233.42 +/- 15.2 Omega.cm2 at day 8 in culture and remained constant through day 14 in culture. The transepithelial permeability coefficients (Papp) at pH 7.4 ranged from 0.58 x 10(-6) cm/s for the hydrophilic marker, mannitol, to 43. 5 x 10(-6) cm/s for the most lipophilic molecule, testosterone. The Papp at pH 7.4 for phenylephrine was 4.21 x 10(-6) cm/s. The Papp values and the lag times of the three esters of phenylephrone were pH dependent. The Papp for 1, 2, and 3 at pH 7.4 were 14.76 x 10(-6), 13.19 x 10(-6), and 12.86 x 10(-6) cm/s, respectively and the permeabilities decreased at conditions below pH 7.4. The lag times at pH 7.4 were 0.10, 0.17, and 0.12 h for 1, 2, and 3, respectively, and the values increased at lower pH conditions. The TEER values of SIRC cell line observed at day 8 to day 14 in the present investigation are similar to the resistance value reported for rabbit cornea (2 kOmega.cm2). All the esters showed significantly (p < 0.05) higher permeabilities than phenylephrine at pH 7.4. The rate and extent of transport of the drugs

  1. Intraplacental Gene Therapy with Ad-IGF-1 Corrects Naturally Occurring Rabbit Model of Intrauterine Growth Restriction

    PubMed Central

    Keswani, Sundeep G.; Balaji, Swathi; Katz, Anna B.; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles

    2015-01-01

    Abstract Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal–fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical

  2. Diastolic Calcium Release Controls the Beating Rate of Rabbit Sinoatrial Node Cells: Numerical Modeling of the Coupling Process

    PubMed Central

    Maltsev, Victor A.; Vinogradova, Tatiana M.; Bogdanov, Konstantin Y.; Lakatta, Edward G.; Stern, Michael D.

    2004-01-01

    Recent studies employing Ca2+ indicators and confocal microscopy demonstrate substantial local Ca2+ release beneath the cell plasma membrane (subspace) of sinoatrial node cells (SANCs) occurring during diastolic depolarization. Pharmacological and biophysical experiments have suggested that the released Ca2+ interacts with the plasma membrane via the ion current (INaCa) produced by the Na+/Ca2+ exchanger and constitutes an important determinant of the pacemaker rate. This study provides a numerical validation of the functional importance of diastolic Ca2+ release for rate control. The subspace Ca2+ signals in rabbit SANCs were measured by laser confocal microscopy, averaged, and calibrated. The time course of the subspace [Ca2+] displayed both diastolic and systolic components. The diastolic component was mainly due to the local Ca2+ releases; it was numerically approximated and incorporated into a SANC cellular electrophysiology model. The model predicts that the diastolic Ca2+ release strongly interacts with plasma membrane via INaCa and thus controls the phase of the action potential upstroke and ultimately the final action potential rate. PMID:15041695

  3. Identification of superficial Candida albicans germ tube antigens in a rabbit model of disseminated candidiasis. A proteomic approach.

    PubMed

    Sáez-Rosón, Aranzazu; Sevilla, María-Jesús; Moragues, María-Dolores

    2014-03-01

    The diagnosis of invasive candidiasis remains a clinical challenge. The detection by indirect immunofluorescence of Candida albicans germ-tube-specific antibodies (CAGTA), directed against germ-tube surface antigens, is a useful diagnostic tool that discriminates between colonization and invasion. However, the standardization of this technique is complicated by its reliance on subjective interpretation. In this study, the antigenic recognition pattern of CAGTA throughout experimental invasive candidiasis in a rabbit animal model was determined by means of 2D-PAGE, Western blotting, and tandem mass spectrometry (MS/MS). Seven proteins detected by CAGTA were identified as methionine synthase, inositol-3-phosphate synthase, enolase 1, alcohol dehydrogenase 1,3-phosphoglycerate kinase, 14-3-3 (Bmhl), and Egd2. To our knowledge, this is the first report of antibodies reacting with Bmhl and Egd2 proteins in an animal model of invasive candidiasis. Although all of the antigens were recognized by CAGTA in cell-wall dithiothreitol extracts of both germ tubes and blastospores of C. albicans, immunoelectron microscopy study revealed their differential location, as the antigens were exposed on the germ-tube cell-wall surface but hidden in the inner layers of the blastospore cell wall. These findings will contribute to developing more sensitive diagnostic methods that enable the earlier detection of invasive candidiasis.

  4. Ultrastructural analysis of the decellularized cornea after interlamellar keratoplasty and microkeratome-assisted anterior lamellar keratoplasty in a rabbit model

    PubMed Central

    Hashimoto, Yoshihide; Hattori, Shinya; Sasaki, Shuji; Honda, Takako; Kimura, Tsuyoshi; Funamoto, Seiichi; Kobayashi, Hisatoshi; Kishida, Akio

    2016-01-01

    The decellularized cornea has received considerable attention for use as an artificial cornea. The decellularized cornea is free from cellular components and other immunogens, but maintains the integrity of the extracellular matrix. However, the ultrastructure of the decellularized cornea has yet to be demonstrated in detail. We investigated the influence of high hydrostatic pressure (HHP) on the decellularization of the corneal ultrastructure and its involvement in transparency, and assessed the in vivo behaviour of the decellularized cornea using two animal transplantation models, in relation to remodelling of collagen fibrils. Decellularized corneas were prepared by the HHP method. The decellularized corneas were executed by haematoxylin and eosin and Masson’s trichrome staining to demonstrate the complete removal of corneal cells. Transmission electron microscopy revealed that the ultrastructure of the decellularized cornea prepared by the HHP method was better maintained than that of the decellularized cornea prepared by the detergent method. The decellularized cornea after interlamellar keratoplasty and microkeratome-assisted anterior lamellar keratoplasty using a rabbit model was stable and remained transparent without ultrastructural alterations. We conclude that the superior properties of the decellularized cornea prepared by the HHP method were attributed to the preservation of the corneal ultrastructure. PMID:27291975

  5. Preclinical Model To Test Human Papillomavirus Virus (HPV) Capsid Vaccines In Vivo Using Infectious HPV/Cottontail Rabbit Papillomavirus Chimeric Papillomavirus Particles▿

    PubMed Central

    Mejia, Andres F.; Culp, Timothy D.; Cladel, Nancy M.; Balogh, Karla K.; Budgeon, Lynn R.; Buck, Christopher B.; Christensen, Neil D.

    2006-01-01

    A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach. PMID:17005666

  6. Effect of Bone Mineral Density on Rotator Cuff Tear: An Osteoporotic Rabbit Model

    PubMed Central

    Chen, Xiaobin; Giambini, Hugo; Ben-Abraham, Ephraim; An, Kai-Nan; Nassr, Ahmad; Zhao, Chunfeng

    2015-01-01

    Introduction An increased bone mineral density (BMD) in the proximity to tendon insertion can improve rotator cuff repair and healing. However, how a decrease of BMD in the humeral head affects the biomechanical properties of the rotator cuff tendon is still unclear. Previous studies have demonstrated ovariectomy in animals to lead to osteoporosis and decreased BMD, and Teriparatide (PTH) administration to improve BMD and strength of bone. This study aimed to explore the correlation between humeral head BMD and infraspinatus (ISP) tendon insertion strength, and if an increase in bone quantity of the humeral head can improve the strength of the rotator cuff. Materials and Methods Eighteen New England white rabbits were divided into the 3 groups: Control, Ovariectomy-Saline (OVX-Saline), and Ovariectomy-PTH (OVX-PTH). The OVX-Saline group and the OVX-PTH were administered daily saline and Teriparatide injections for 8 weeks starting at 17 weeks of OVX. BMD of the humeral head was measured, the ISP tendon failure load was tested and the failure stress was calculated. One specimen from each group was used for histological analysis. Linear regression analysis was used to derive equations for the BMD and failure stress. Results Significant differences were observed in the measured humeral head BMD of the Control and OVX-PTH groups compared to the OVX-Saline group (P = 0.0004 and P = 0.0024, respectively). No significant difference was found in failure stress among the three groups, but an expected trend with the control group and OVX-PTH group presenting higher failure strength compared to the OVX-Saline group. BMD at the humeral head showed a positive linear correlation with stress (r2 = 0.54). Histology results showed the superiority in OVX-PTH group ISP enthesis compared to the OVX-Saline group. Conclusion Bone loss of the humeral head leads to decreased tendon/bone insertion strength of the infraspinatus tendon enthesis. Teriparatide administration can increase bone

  7. Diaphragm Repair with a Novel Cross-Linked Collagen Biomaterial in a Growing Rabbit Model

    PubMed Central

    Mayer, Steffi; Decaluwe, Herbert; Ruol, Michele; Manodoro, Stefano; Kramer, Manuel; Till, Holger; Deprest, Jan

    2015-01-01

    Background Neonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes. Materials and Methods 2.0x1.0 cm diaphragmatic defects were created in 6-weeks old New-Zealand white rabbits. We compared reconstruction with a purpose-designed cross-linked ACM (Matricel) to 4-layer non-cross-linked small intestinal submucosa (SIS) and a 1-layer synthetic Dual Mesh (Gore-Tex). Unoperated animals or animals undergoing primary closure (4/0 polyglecaprone) served as age-matched controls. 60 (n = 25) resp. 90 (n = 17) days later, animals underwent chest x-ray and obduction for gross examination of explants, scoring of adhesion and inflammatory response. Also, uniaxial tensiometry was done, comparing explants to contralateral native diaphragmatic tissue. Results Overall weight nearly doubled from 1,554±242 g at surgery to 2,837±265 g at obduction (+84%). X-rays did show rare elevation of the left diaphragm (SIS = 1, Gore-Tex = 1, unoperated control = 1), but no herniation of abdominal organs. 56% of SIS and 10% of Matricel patches degraded with visceral bulging in four (SIS = 3, Matricel = 1). Adhesion scores were limited: 0.5 (Matricel) to 1 (SIS, Gore-Tex) to the left lung (p = 0.008) and 2.5 (Gore-Tex), 3 (SIS) and 4 (Matricel) to the liver (p<0.0001). Tensiometry revealed a reduced bursting strength but normal compliance for SIS. Compliance was reduced in Matricel and Gore-Tex (p<0.01). Inflammatory response was characterized by a more polymorphonuclear cell (SIS) resp. macrophage (Matricel) type of infiltrate (p<0.05). Fibrosis was similar for all groups, except there was less mature collagen deposited to Gore-Tex implants (p<0.05). Conclusions Matricel induced a macrophage-dominated inflammatory response, more adhesions, had appropriate strength but a

  8. Competition for Materno-Fetal Resource Partitioning in a Rabbit Model of Undernourished Pregnancy

    PubMed Central

    Lopez-Tello, Jorge; Arias-Alvarez, Maria; Jimenez-Martinez, Maria Angeles; Garcia-Garcia, Rosa Maria; Rodriguez, Maria; Lorenzo Gonzalez, Pedro Luis; Bermejo-Poza, Ruben; Garcia Rebollar, Pilar

    2017-01-01

    The major goal of animal production is to obtain abundant and healthy meat for consumers. Maternal food restriction (MFR) is often applied in farms to reduce production costs. However, the suitability of MFR in livestock animals is questionable, as this management may compromise maternal fitness due to a severe negative energetic balance and can induce Intrauterine Growth Restriction (IUGR) and prenatal programming in the offspring. Here, we sought to determine, using pregnant rabbits, the consequences of MFR on maternal endocrine and metabolic status and conceptus development. Pregnant dams were distributed into three groups: CONTROL (ad libitum feeding throughout the entire pregnancy; mean pregnancy length being around 31 days), UNDERFED (50% MFR during the entire pregnancy) and EARLY-UNDERFED (50% MFR only during the preimplantation period, Days 0–7). Maternal leptin concentrations and glycemic and lipid profiles were determined throughout pregnancy, whilst conceptus development was assessed ex-vivo at Day 28. Placental parameters were determined by macroscopic and histological evaluations and apoptotic assessments (TUNEL and Caspase-3). The main results of the study showed that, despite MFR altered maternal plasma lipid concentration (P<0.05), there were no effects on maternal bodyweight, plasma leptin concentration or glycemic profile. Fetal crown-rump lengths were reduced in both undernourished groups (P<0.001), but a significant reduction in fetal weight was only observed in the UNDERFED group (P<0.001). Growth in both undernourished groups was asymmetrical, with reduced liver weight (P<0.001) and significantly increased brain: fetal weight-ratio (P<0.001) and brain: liver weight-ratio (P<0.001) when compared to the CONTROL group. A significant reduction in placental weight was only observed in the UNDERFED group (P<0.001), despite both undernourished groups showing higher apoptotic rates at decidua and labyrinth zone (P<0.05) than the CONTROL group. Thus

  9. Evaluation of the Efficacy of Modified Vaccinia Ankara (MVA)/IMVAMUNE (registered trademark) Against Aerosolized Rabbitpox Virus in a Rabbit Model

    DTIC Science & Technology

    2009-01-01

    rabbitpox virus in a rabbit model icole L. Garzaa, Josh M. Hatkina, Virginia Livingstona, Donald K. Nicholsb, aul J. Chaplind, Ariane Volkmannd, Diana...eywords: abbitpox virus a b s t r a c t Infection of rabbitswith aerosolized rabbitpox virus (RPXV) produces a disease similar tomonkeypox and smallpox...irus, amember of the genusOrthopoxvirus in the family Poxviridae. ther orthopoxviruses that can infect humans include monkeypox irus, cowpox virus , and

  10. Daptomycin versus Vancomycin in a Methicillin-Resistant Staphylococcus aureus Endophthalmitis Rabbit Model: Bactericidal Effect, Safety, and Ocular Pharmacokinetics

    PubMed Central

    Saleh, Maher; Marcellin, Luc; Subilia, Audrey; Bourcier, Tristan; Prévost, Gilles; Jehl, François

    2012-01-01

    Staphylococcus aureus is a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistant S. aureus endophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups (n = 8) and one untreated group (n = 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures (P < 0.05). The elimination half-life (t1/2β) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than the t1/2β of vancomycin (20.5 ± 2.0 h for the VAN 1 group) (P < 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria. PMID:22371888

  11. Alveolarization Genes Modulated by Fetal Tracheal Occlusion in the Rabbit Model for Congenital Diaphragmatic Hernia: A Randomized Study

    PubMed Central

    Vuckovic, Aline; Herber-Jonat, Susanne; Flemmer, Andreas W.; Roubliova, Xenia I.; Jani, Jacques C.

    2013-01-01

    Background The mechanisms by which tracheal occlusion (TO) improves alveolarization in congenital diaphragmatic hernia (CDH) are incompletely understood. Therefore transcriptional and histological effects of TO on alveolarization were studied in the rabbit model for CDH. The question of the best normalization strategy for gene expression analysis was also addressed. Methods Fetal rabbits were randomized for CDH or sham operation on gestational day 23/31 and for TO or sham operation on day 28/31 resulting in four study groups. Untouched littermates were added. At term and before lung harvest, fetuses were subjected to mechanical ventilation or not. Quantitative real-time PCR was performed on lungs from 4–5 fetuses of each group with and without previous ventilation. Stability of ten housekeeping genes (HKGs) and optimal number of HKGs for normalization were determined, followed by assessment of HKG expression levels. Expression levels of eleven target genes were studied in ventilated lungs, including genes regulating elastogenesis, cell-environment interactions, and thinning of alveolar walls. Elastic staining, immunohistochemistry and Western blotting completed gene analysis. Results Regarding HKG expression, TO increased β-actin and β-subunit of ATP synthase. Mechanical ventilation increased β-actin and β2-microglobulin. Flavoprotein subunit of succinate dehydrogenase and DNA topoisomerase were the most stable HKGs. CDH lungs showed disorganized elastin deposition with lower levels for tropoelastin, fibulin-5, tenascin-C, and α6-integrin. After TO, CDH lungs displayed a normal pattern of elastin distribution with increased levels for tropoelastin, fibulin-5, tenascin-C, α6-integrin, ß1-integrin, lysyl oxidase, and drebrin. TO increased transcription and immunoreactivity of tissue inhibitor of metalloproteinase-1. Conclusions Experimental TO might improve alveolarization through the mechanoregulation of crucial genes for late lung development. However part

  12. Countercurrent transfer of dopamine from venous blood in the cavernous sinus to the arterial blood supplying the brain - the perfused rabbit head as an experimental model.

    PubMed

    Muszak, J; Krzymowski, T; Gilun, P; Stefanczyk-Krzymowska, S

    2014-10-01

    The objective of the current study was to check whether countercurrent transfer of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit can be used as an animal model to study cavernous sinus function. After exsanguination of the animal, oxygenated and warmed (37°C) Hanseneleit-Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm Hg) and radiolabeled dopamine (3(H)-DA, 10 μCi) was infused into the cavernous sinus through the angular oculi vein. Cerebral blood from the basilar artery was collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10 minutes after completion of infusion. Selected brain tissue samples were collected after completion of the head perfusion. It was demonstrated that dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid artery supplying the brain. Dopamine permeation was greater when the rabbit head was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When the head was perfused with buffer and blood in a 3:1 ratio, significant radioactivity was found in samples collected from the brain basilar artery during and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13 ± 2.7% unmetabolized 3(H)-DA and 65.9 ± 2.7% its metabolites. Significant radioactivity was also found in some brain tissue samples in both groups (P<0.05). The concentration of free radiolabeled dopamine particles in the dialysate of blood plasma and plasma diluted with buffer did not differ significantly. Because the structures of the cavernous sinus and cavernous fragment of the internal carotid artery of the rabbit are similar to those in humans, it suggests that rabbits can serve as a model for experimental physiological studies of cavernous sinus function and retrograde dopamine transfer in the cavernous sinus should be considered as an important link in

  13. Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model

    PubMed Central

    Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

    2016-01-01

    The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration. PMID:27748828

  14. Corneal regeneration by transplantation of corneal epithelial cell sheets fabricated with automated cell culture system in rabbit model.

    PubMed

    Kobayashi, Toyoshige; Kan, Kazutoshi; Nishida, Kohji; Yamato, Masayuki; Okano, Teruo

    2013-12-01

    We have performed clinical applications of cell sheet-based regenerative medicine with human patients in several fields. In order to achieve the mass production of transplantable cell sheets, we have developed automated cell culture systems. Here, we report an automated robotic system utilizing a cell culture vessel, cell cartridge. The cell cartridge had two rooms for epithelial cells and feeder layer cells separating by porous membrane on which a temperature-responsive polymer was covalently immobilized. After pouring cells into this robotic system, cell seeding, medium change, and microscopic examination during culture were automatically performed according to the computer program. Transplantable corneal epithelial cell sheets were successfully fabricated in cell cartridges with this robotic system. Then, fabricated cell sheets were transplanted onto ocular surfaces of rabbit limbal epithelial stem cell deficiency model after 6-h transportation using a portable homothermal container to keep inner temperature at 36 °C. Within one week after transplantation, normal corneal epithelium was successfully regenerated. This automatic cell culture system would be useful for industrialization of tissue-engineered products for regenerative medicine.

  15. Repair of segmental long bone defect in a rabbit radius nonunion model: comparison of cylindrical porous titanium and hydroxyapatite scaffolds.

    PubMed

    Zhang, Ming; Wang, Guang-lin; Zhang, Hong-fang; Hu, Xu-dong; Shi, Xiao-yuan; Li, Sen; Lin, Wei

    2014-06-01

    A segmental long bone defect in a rabbit radius nonunion model was repaired using cylindrical porous titanium (Ti) and hydroxyapatite (HA) scaffolds. Each scaffold was produced using the same method, namely, a slurry foaming method. Repairing ability was characterized using x-radiographic score 12 and 24 weeks postprocedure; failure load of the radius-ulna construct, under three-point bending, 12 weeks postprocedure; and the percentage of newly formed bone within the implant, 12 and 24 weeks after postprocedure. For each of these parameters, the difference in the results when porous Ti scaffold was used compared with when HA scaffolds were used was not significant; both porous scaffolds showed excellent repairing ability. Because the trabecular bone is a porous tissue, the interconnected porous scaffolds have the advantages of natural bone, and vasculature can grow into the porous structure to accelerate the osteoconduction and osteointegration between the implant and bone. The porous Ti scaffold not only enhanced the bone repair process, similar to porous HA scaffolds, but also has superior biomechanical properties. The present results suggest that porous Ti scaffolds may have promise for use in the clinical setting.

  16. Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.

    PubMed

    Chen, Guobao; Yang, Li; Lv, Yonggang

    2016-04-01

    To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing.

  17. The effect of topical dexamethasone and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit

    SciTech Connect

    Miller, M.H.; Grierson, I.; Unger, W.G.; Hitchings, R.A. )

    1990-01-01

    We studied the effect of topical dexamethasone (1%) and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit. Intraocular pressure and gross facility of aqueous outflow following surgery were not influenced by either treatment, although blebs persisted longer in the irradiated eyes. Steroids reduced clinically observable inflammation as well as the number of inflammatory cells identifiable by microscopy. Fibroblast production temporarily slowed, and ultrastructural examination demonstrated lipid-filled vacuoles and dilated mitochondria in these eyes. Also, the scar was thinner at 24 days. Beta irradiation delayed wound healing and the scar was thinner in the early postoperative stages, but the light microscopic appearance of the scar was unaltered at 59 days. Inflammation was more pronounced initially, with abundant fibrin in the wound. Recovery of the conjunctival epithelium was delayed. The delay in fibroblast recruitment and wound contraction, the thinner scar tissue, and the increased survival of the bleb are all factors that suggest that beta irradiation may be a useful adjunct to glaucoma surgery.

  18. Middle ear mucosal regeneration with three-dimensionally tissue-engineered autologous middle ear cell sheets in rabbit model.

    PubMed

    Yaguchi, Yuichiro; Murakami, Daisuke; Yamato, Masayuki; Hama, Takanori; Yamamoto, Kazuhisa; Kojima, Hiromi; Moriyama, Hiroshi; Okano, Teruo

    2016-03-01

    The likelihood of recurrent retraction and adhesion of newly formed tympanic membrane is high when middle ear mucosa is extensively lost during cholesteatoma and adhesive otitis media surgery. If rapid postoperative regeneration of the mucosa on the exposed bone surface can be achieved, prevention of recurrent eardrum adhesion and cholesteatoma formation, for which there has been no definitive treatment, can be expected. Suture-less transplantation of tissue-engineered mucosal cell sheets was examined immediately after the operation of otitis media surgery in order to quickly regenerate middle ear mucosa lost during surgery in a rabbit model. Transplantable middle ear mucosal cell sheets with a three-dimensional tissue architecture very similar to native middle ear mucosa were fabricated from middle ear mucosal tissue fragments obtained in an autologous manner from middle ear bulla on temperature-responsive culture surfaces. Immediately after the mucosa was resected from middle ear bone bulla inner cavity, mucosal cell sheets were grafted at the resected site. Both bone hyperplasia and granulation tissue formation were inhibited and early mucosal regeneration was observed in the cell sheet-grafted group, compared with the control group in which only mucosal removal was carried out and the bone surface exposed. This result indicates that tissue engineered mucosal cell sheets would be useful to minimize complications after the surgical operation on otitis media and future clinical application is expected.

  19. Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

    PubMed

    Mikolka, P; Kopincová, J; Košútová, P; Čierny, D; Čalkovská, A; Mokrá, D

    2016-12-22

    Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

  20. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned.

  1. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    PubMed

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  2. An overview on development and application of an experimental platform for quantitative cardiac imaging research in rabbit models of myocardial infarction

    PubMed Central

    Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond

    2014-01-01

    To exploit the advantages of using rabbits for cardiac imaging research and to tackle the technical obstacles, efforts have been made under the framework of a doctoral research program. In this overview article, by cross-referencing the current literature, we summarize how we have developed a preclinical cardiac research platform based on modified models of reperfused myocardial infarction (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be closely matched with those ex vivo macro- and microscopic findings; how these imaging outcomes could be quantitatively analyzed, validated and demonstrated; and how we could apply this cardiac imaging platform to provide possible solutions to certain lingering diagnostic and therapeutic problems in experimental cardiology. In particular, tissue components in acute cardiac ischemia have been stratified and characterized, post-infarct lipomatous metaplasia (LM) as a common but hardly illuminated clinical pathology has been identified in rabbit models, and a necrosis avid tracer as well as an anti-ischemic drug have been successfully assessed for their potential utilities in clinical cardiology. These outcomes may interest the researchers in the related fields and help strengthen translational research in cardiovascular diseases. PMID:25392822

  3. Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits.

    PubMed

    Nie, Maoxiao; Yan, Yunfeng; Li, Xinhe; Feng, Tingting; Zhao, Xin; Zhang, Mingduo; Zhao, Quanming

    2016-01-01

    Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5-146.8%, and 241.5-255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate.

  4. Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits

    PubMed Central

    Nie, Maoxiao; Yan, Yunfeng

    2016-01-01

    Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5–146.8%, and 241.5–255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate. PMID:27965979

  5. Evaluation of the histological and mechanical features of tendon healing in a rabbit model with the use of second-harmonic-generation imaging and tensile testing

    PubMed Central

    Hase, E.; Sato, K.; Yonekura, D.; Minamikawa, T.; Takahashi, M.

    2016-01-01

    Objectives This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing. Materials and Methods A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation. Results While the SHG light intensity of the healing tendon samples was significantly lower than that of the uninjured tendon samples, 2D Fourier transform SHG images showed a clear difference in collagen fibre structure between the uninjured and the healing samples, and among the healing samples. The mean intensity of the SHG image showed a moderate correlation (R2 = 0.37) with Young’s modulus obtained from the tensile testing. Conclusion Our results indicate that SHG microscopy may be a potential indicator of tendon healing. Cite this article: E. Hase, K. Sato, D. Yonekura, T. Minamikawa, M. Takahashi, T. Yasui. Evaluation of the histological and mechanical features of tendon healing in a rabbit model with the use of second-harmonic-generation imaging and tensile testing. Bone Joint Res 2016;5:577–585. DOI: 10.1302/2046-3758.511.BJR-2016-0162.R1. PMID:27881441

  6. Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery

    PubMed Central

    Kang, Hyun; Chung, Yoon Sang; Kim, Sang Wook; Choi, Geun Joo; Kim, Beom Gyu; Park, Suk Won; Seok, Ju Won; Hong, Joonhwa

    2015-01-01

    Objective We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. Methods A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. Results In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. Conclusions In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required. PMID:26580394

  7. Infliximab’s influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model

    PubMed Central

    2014-01-01

    Background Infliximab, a TNF-α inhibitor, is a potent anti-inflammatory drug in the treatment of inflammatory bowel diseases. Recent studies have investigated the effect of infliximab treatment on postoperative complications such as anastomotic leakage, however, with conflicting results and conclusions. The purpose of this study was to investigate whether a single dose infliximab has an adverse effect on the anastomotic healing process, observed as reduced anastomotic breaking strength and histopathologically verified lower grade of inflammatory response, in the small intestine of a rabbit. Methods Thirty New Zealand rabbits (median weight 2.5 kg) were allocated to treatment with an intravenous bolus of either 10 mg/kg infliximab (n = 15) or placebo (n = 15). One week later all rabbits underwent two separate end-to-end anastomoses in the jejunum under general anesthesia. At postoperative day three, the anastomotic breaking strength was determined and histopathological changes were examined. Results The mean value of anastomotic breaking strength in the placebo group was 1.89 ± 0.36 N and the corresponding value was 1.81 ± 0.33 N in the infliximab treated rabbits. There was no statistically significant difference between the groups (p = 0.51). The infliximab-treated rabbits had a significant lower degree of inflammatory infiltration response compared to the placebo group (p = 0.047). Conclusions Our conclusion, limited by the small sample sizes in both groups, is that a single dose of infliximab, given one week prior to surgery, does not have an impact on the anastomotic breaking strength on the third postoperative day in the small intestine of rabbits. PMID:24762063

  8. Effects of locally applied nerve growth factor to the inferior alveolar nerve histology in a rabbit model of mandibular distraction osteogenesis.

    PubMed

    Wang, L; Zhao, Y; Cheng, X; Yang, Y; Liu, G; Ma, Q; Shang, H; Tian, L; Lei, D

    2009-01-01

    Distraction osteogenesis (DO) is widely used in deformities and defects of the craniofacial bone. Accelerating inferior alveolar nerve (IAN) recovery would aid the process. Nerve growth factor (NGF) plays a vital role in peripheral nerve regeneration. In this study, the ability of locally applied human NGF beta (hNGFbeta) to enhance the morphological recovery of the IAN in a rabbit model of mandibular DO was studied. Rabbits underwent bilateral DO with a rate of 0.5mm per 12h. Two doses of 40 microg hNGFbeta in buffer were injected into callus at the beginning the of consolidation time. The contralateral side received injections of placebo. Rabbits were killed at 14 and 28 days. IAN specimens were subjected to histological and histomorphometric analysis. In both 14 and 28 days consolidation experiments, nerve histological analysis showed less degeneration and more regeneration in nerve fibers on the hNGFbeta treated side than the control side. Histomorphometric analysis showed that the myelinated fiber density on the hNGFbeta treated side was significantly higher than on the control side (p<0.01). The data indicate that locally applied hNGFbeta can accelerate the morphological recovery of the IAN and may play a role in reducing nerve injury in mandibular DO clinically.

  9. Nerve growth factor injected systemically improves the recovery of the inferior alveolar nerve in a rabbit model of mandibular distraction osteogenesis.

    PubMed

    Du, Zhao-jie; Wang, Lei; Lei, De-lin; Liu, Bao-lin; Cao, Jian; Zhang, Pu; Ma, Qin

    2011-10-01

    Our aim was to find out if nerve growth factor (NGF) injected systemically could improve the recovery of the inferior alveolar nerve in a rabbit model of mandibular distraction osteogenesis. We used 48 New Zealand white rabbits that were treated with bilateral distraction osteogenesis at a rate of 0.5mm/12h for 10 days. Immediately postoperatively, NGF or sodium chloride 0.6 μg/day was injected intramuscularly for 20 days. At the end of distraction and after consolidation times of 1, 2, and 4 weeks, the inferior alveolar nerves were evaluated histologically and histomorphometrically. Histologically, at 2 and 4 weeks there was less myelin debris, and more regenerating axons were present, in the NGF than the control groups. The density of myelinated axons was significantly greater in groups with NGF than controls at 2 and 4 weeks (p<0.05). NGF given systemically can accelerate the recovery of the inferior alveolar nerve in rabbits after mandibular distraction osteogenesis, and is a promising treatment option for neurological complications of mandibular distraction osteogenesis.

  10. Variation of plasma levels of endothelin, calcitonin gene-related peptide, nitric oxide, and malondialdehyde in acute myocardial ischemia reperfusion injury in a rabbit model.

    PubMed

    Zhao, Y B; Wang, Y Z; Yue, Y H; Zhao, W C; Feng, G X

    2015-05-25

    We examined the variation in plasma levels of endothelin (ET), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) activity, in acute myocardial ischemia reperfusion injury in a rabbit model. Seventy rabbits were randomly assigned into 3 groups. Open-chest surgery (OCS) was performed for all rabbits. Group A (N = 20) received sham-surgery, group B (N = 25) was the reperfusion group, and group C (N = 25) was the infarction group. At 12 h after chest clo-sure, plasma ET levels in groups B and C were clearly increased, while CGRP levels were clearly decreased, particularly in group B. At 24 h after chest closure, ET levels were higher than before OCS, while there was no significant difference between groups B and C. ET in group B was decreased, while that in group C was increased at 12 h. No significant difference in CGRP was observed between 12 and 24 h after chest closure. NO levels in groups B and C at 12 h after chest closure were significantly decreased compared to those before OCS. NO levels in group B at 24, 48, and 72 h were significantly lower than those at 12 h, while those of group C were not significantly changed after 12 h. Dynamic monitoring and comparison of plasma levels of ET, CGRP, NO, and MDA as well as SOD activity revealed that appropriate intervention of these factors may reduce reperfusion injury.

  11. Use of N,O-carboxymethyl chitosan to prevent postsurgical adhesions in a rabbit double uterine horn model: a randomized controlled design.

    PubMed

    Ren, Chang; Zhao, Dachun; Zhu, Lan

    2016-05-01

    In previous studies, N,O-carboxymethyl chitosan has been shown to decrease the incidence and intensity of abdominal adhesions. In the present study, adhesions were induced in 220 rabbits using a double uterine horn model. Rabbits were randomized to receive an operation only or an operation+medical chitosan intraperitoneally. Twenty-two rabbits from each group were euthanized at one of five different times (Day 3, 7, 14, 28, or 42), and adhesion formation was given gross and histopathological scores. Reductions were observed in adhesion extent (P=0.0337) and tenacity (P=0.0271) as well as inflammation (P<0.0001) on Day 3 when medical chitosan was applied. Prior to Day 14, fibrosis was less obvious in the medical chitosan group (P< 0.0005). The tenacity scores were significantly lower in the medical chitosan group following Day 14 (P<.05), while the type scores were lower in the medical chitosan group following Day 28 (P<.03). Thus, medical chitosan decreased both the gross and the histopathological scores of the induced adhesions.

  12. Continuous intraocular pressure measurement by telemetry in alpha-chymotrypsin-induced glaucoma model in the rabbit: effects of timolol, dorzolamide, and epinephrine.

    PubMed

    Percicot, C L; Schnell, C R; Debon, C; Hariton, C

    1996-12-01

    The aim of this study was to set-up and validate the use of a radio-telemetry system in order to record IOP in chronic ocular hypertensive animals. The transmitter of a miniaturized radio-telemetry system was implanted in rabbits, and its catheter was tunnelled subcutaneously to the superior conjunctival sac and inserted into the midvitreous. Implantation was performed in chronic ocular hypertensive rabbits induced by an injection of alpha-chymotrypsin into the posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide hydrochloride and 1% epinephrine were assessed and compared after topical administration in this model. Implanted radio-telemetric system into the vitreous allowed IOP measurement for more than 6 months. In this study, circadian IOP kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol maleate was found significantly potent in reducing IOP, while changes depended on the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP reduction and was found to be also well effective at night. We evidenced a biphasic time-dependent effect after topical epinephrine, with a long lasting IOP increase occurring after the administration. This change was found to be related to side effects resulting from a poor ocular tolerance of this drug in the rabbit, leading to either a complete eye closure or a higher blinking rate. By using our method, we confirmed the pressure pulses and undershoots occurring during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined method to assess anti-glaucoma drug activity, 24 hours a day, for long-term periods in unrestrained animals, while also providing information on the ocular side effects of eye drops.

  13. A novel atheroprotective role of MF59-like adjuvant when co-administered with CETP vaccine in rabbit model of atherosclerosis

    PubMed Central

    Aghebati, Tamara; Mohammadpour, Amir Hooshang; Afshar, Mohammad; Jaafari, Mahmoud Reza; Abnous, Khalil; Nazemi, Saeed; Issazadeh, Sobhan; Hashemzadeh, Saeed; Zare, Mohammad; Badiee, Ali

    2016-01-01

    Objective(s): In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice. Materials and Methods: Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis. Anti-TT-CETP specific antibody, CETP activity in sera and mRNA level of cytokine IL-4 and IFN-γ in peripheral mononuclear cells were determined. Therapeutic response was also examined by tracking serum lipoprotein levels and pathologic observation of atherosclerotic lesions at aortic site. Results: More anti-TT-CETP antibody was found in Alum/CpG vaccinated rabbits compared to buffer (P<0.001). Antibody induced by MF59-like formulation was not significantly higher than buffer. CETP activity and lipoprotein levels were not significantly different between vaccinated and control rabbits. The mRNA level of IL-4 was significantly lower than buffer while, IFN-γ gene expression was significantly higher in both vaccinated groups. Atherosclerosis thickness grade of aorta was dramatically lower than buffer (P<0.01) in both vaccinated groups. Conclusion: It is concluded that MF59-adjuvanted CETP vaccine showed anti-atherosclerosis properties, but the protective effect could not be directly attributed to the immune response induced by anti TT-CETP antibody and CETP inhibition. Further studies are needed to explain the anti-atherosclerosis properties of MF59 in the presence of TT-CETP peptide. PMID:28096968

  14. A new osteophyte segmentation method with applications to an anterior cruciate ligament transection rabbit femur model via micro-CT imaging

    NASA Astrophysics Data System (ADS)

    Liang, G.; Elkins, J. M.; Coimbra, A.; Duong, L. T.; Williams, D. S.; Sonka, M.; Saha, P. K.

    2010-03-01

    Osteophyte is an additional bony growth on a normal bone surface limiting or stopping motion in a deteriorating joint. Detection and quantification of osteophytes from CT images is helpful in assessing disease status as well as treatment and surgery planning. However, it is difficult to segment osteophytes from healthy bones using simple thresholding or edge/texture features in CT imaging. Here, we present a new method, based on active shape model (ASM), to solve this problem and evaluate its application to ex vivo μCT images in an ACLT rabbit femur model. The common idea behind most ASM based segmentation methods is to first build a parametric shape model from a training dataset and during application, find a shape instance from the model that optimally fits to target image. However, it poses a fundamental difficulty for the current application because a diseased bone shape is significantly altered at regions with osteophyte deposition misguiding an ASM method that eventually leads to suboptimum segmentation results. Here, we introduce a new partial ASM method that uses bone shape over healthy regions and extrapolate its shape over diseased region following the underlying shape model. Once the healthy bone region is detected, osteophyte is segmented by subtracting partial-ASM derived shape from the overall diseased shape. Also, a new semi-automatic method is presented in this paper for efficiently building a 3D shape model for rabbit femur. The method has been applied to μCT images of 2-, 4-, and 8-week post ACLT and sham-treated rabbit femurs and results of reproducibility and sensitivity analyses of the new osteophyte segmentation method are presented.

  15. Alpha-2-macroglobulin as the major defence in acute pseudomonal septic shock in the guinea-pig model.

    PubMed Central

    Khan, M. M.; Shibuya, Y.; Nakagaki, T.; Kambara, T.; Yamamoto, T.

    1994-01-01

    An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces immediate lethal shock in guinea-pigs. In the present study, alpha-2-macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma that inhibits the enzymatic activity of elastase in vitro. Depletion of circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2 rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted, indicating that elastase induces shock through activation of the Hageman factor-dependent system. Similar results were obtained when the culture supernatants of an elastase-producing strain, IFO-3455, were used instead of the purified elastase, whereas no cardiovascular changes occurred, even in the alpha 2M-depleted guinea-pigs, when the culture supernatants were pretreated with an elastase specific inhibitor (zincov) or when the culture supernatants of an elastase non-producing strain, PA-103 were used. PMID:7524612

  16. A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model

    PubMed Central

    Lei, Pengfei; Sun, Rongxin; Wang, Long; Zhou, Jialin; Wan, Lifei; Zhou, Tianjian; Hu, Yihe

    2015-01-01

    Background and Objectives Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones. Methods Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials. Results Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones. Conclusions Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting. PMID:26719896

  17. Involvement of necroptosis, a newly recognized cell death type, in steroid-induced osteonecrosis in a rabbit model

    PubMed Central

    Ichiseki, Toru; Ueda, Shusuke; Ueda, Yoshimichi; Tuchiya, Masanobu; Kaneuji, Ayumi; Kawahara, Norio

    2017-01-01

    We investigated the role of programmed necrosis (necroptosis), a newly recognized form of cell necrosis that has been implicated in the development of steroid-induced osteonecrosis. We used an osteonecrosis model in which 30 Japanese white rabbits each weighing 3.5kg were injected once with methylprednisolone at 20 mg/kg body weight into the right gluteal muscle. Ten animals killed 14 days thereafter were designated as S14d groups, while another 10 animals injected with necroptosis, a specific inhibitor of necrostatin-1 i.v. at 1.65mg/kg on the same day as the steroid were also killed on the 14th day and designated as SN14d group. As a control, 10 animals injected only with physiological saline were studied as N group. After the animals were sacrificed the bilateral femoral bone was examined histopathologically and the presence of osteonecrosis determined. Furthermore, animals subjected to the same treatment and killed on the 3rd day after drug administration were set up as S3d group and SN3d group, and Western blotting of Receptor-interacting protein ( RIP ) 1 and RIP3 in femoral bone performed. The osteonecrosis rate was 70% in S14d group, and 0% in both N and SN groups. In 2 of 10 animals in SN group fatty marrow was found. On Western blotting significantly increased expression of both RIP1 and RIP3 was noted in S3d group, confirming that Nec-1 was suppressed. Necroptosis mediated by RIP1 and RIP3 expression was thought to be implicated in the development of steroid-induced osteonecrosis. Also, by suppressing expression of RIP1 and 3 with the administration of Nec-1 the osteonecrosis rate was significantly decreased. These results suggest that necroptosis may have potential as a novel target for both elucidating the mechanisms underlying steroid-induced osteonecrosis and establishing more effective prophylactic countermeasures. PMID:28260985

  18. Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

    PubMed

    Bayat, Sam; Porra, Liisa; Broche, Ludovic; Albu, Gergely; Malaspinas, Iliona; Doras, Camille; Strengell, Satu; Peták, Ferenc; Habre, Walid

    2015-08-01

    We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

  19. The effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics.

    PubMed

    Williams, J; Gladen, B C; Turner, T W; Schrader, S M; Chapin, R E

    1991-05-01

    Mature (12 months old) male New Zealand White rabbits (8-10/group) were dosed subcutaneously with ethylene dibromide (EDB) in corn oil (untreated and vehicle controls, 15, 30, or 45 mg/kg body wt/day for 5 days). Weekly semen samples (for 6 weeks preexposure, during treatment, and 12 weeks postdosing [pd]) were analyzed for sperm concentration, number, morphology, viability, and motion parameters (velocity, linearity, beat cross-frequency, amplitude of lateral head displacement (ALH), and circularity), and semen pH, osmolality, volume, fructose, citric acid, carnitine, protein, and acid phosphatase (AP). Male fertility was assessed preexposure and at 4 and 12 weeks pd by artificial insemination of three females/male/time point with one million motile sperm. The percentage pregnant females, litter size, fetal body weights, and structural development were assessed. In the 45 mg/kg dose group of males there was 30% mortality and liver damage in 43% of the survivors as evidenced by increased levels of serum enzymes. Also in this group, EDB produced significant decreases in sperm velocity, percentage motility, and ALH (up to 25% at various times pd). There were also dose-related decreases in semen pH (up to 2%) and total ejaculate volume (up to 23%, 15 and 30 mg/kg dose groups only). AP activities were significantly elevated (up to 116%) 2 weeks pd in the 45 mg/kg dose group. All other semen parameters evaluated were unaffected. Male fertility and fetal structural development were also unaffected. Of the seven semen parameters perturbed by EDB in humans (Schrader et al., 1988), four were also affected in the rabbit (sperm velocity, percentage motility, pH, and volume), whereas sperm number, viability, and morphology were not. Thus, some of the male reproductive effects of EDB in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/k